Research Update:Curcumae Longae.Curcuma longa.

  seminal trace...Turmeric extract,Curcuma Root Extract.10:1.Curcumae Longae,Turmeric powder,Turmeric Rhizome.aqueous turmeric extract,Alcoholic turmeric extract,Curcumin,Turmeric extract in water; Turmeric extract in alcohol,whole extract of turmeric root,tumeric extract...

 


   Phytochemical info of Curcumae Longae.Curcuma longa.

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 Definition:Curcumae Longae.Curcuma longa. are majorly composed of
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   Research Update:Curcumae Longae.Curcuma longa.

  Curcumin is a Modulator of Bilayer Material Properties.:Biochemistry. 2007 Aug 17;Ingolfsson HI, Ii RE, Andersen OS.Cornell/Rockefeller/Sloan-Kettering Tri-Institutional Program in Computational Biology & Medicine, New York, New York 10065, Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701.

 Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is the major bioactive compound in turmeric (Curcuma longa) with antioxidant, antiinflammatory, anticarcinogenic, and antimutagenic effects. At low muM concentrations, curcumin modulates many structurally and functionally unrelated proteins, including membrane proteins. Because the cell membranes' lipid bilayer serves as a gate-keeper and regulator of many cell functions, we explored whether curcumin modifies general bilayer properties using channels formed by gramicidin A (gA). gA channels form when two monomers from opposing monolayers associate to form a conducting dimer with a hydrophobic length that is less than the bilayer hydrophobic thickness; gA channel formation thus causes a local bilayer thinning. The energetic cost of this bilayer deformation alters the gA monomer <--> dimer equilibrium, which makes the channels' appearance rate and lifetime sensitive to changes in bilayer material properties, and the gA channels become probes for changes in bilayer properties. Curcumin decreases bilayer stiffness, increasing both gA channel lifetimes and appearance rates, meaning that the energetic cost of the gA-induced bilayer deformation is reduced. These results show that curcumin may exert some of its effects on a diverse range of membrane proteins through a bilayer-mediated mechanism.

  Efficient preparation of liposomes encapsulating food materials using lecithins by a mechanochemical method.:J Oleo Sci. 2006;56(1):35-42.

 In order to evaluate to the feasibility of using lecithins for nanocapsules including functional food materials, liposomes were prepared from different commercially available lecithins (SLP-WHITE, SLP-PC70 and PL30S) by the Bangham method, and their physicochemical properties were examined by using a confocal laser scanning microscopy (CLSM) and the measurements of trapping efficiency. There was little difference in the trapping efficiency among the three types of liposomes. In all cases, the trapping efficiency clearly increased with an increase of the lecithin concentration up to 10 wt % , and the maximum efficiency reached at approximately 15%. CLSM observation showed the particle size of liposomes prepared from SLP-WHITE is significantly smaller than that prepared from other lecithins. In addition, liposomal solution prepared from SLP-WHITE remained well dispersed for at least 30 days, while two other liposomal solutions showed a phase separation due to aggregation and/or fusion of liposomes. These results indicated that SLP-WHITE is the most appropriate for the preparation of stable liposomes with well dispersed among the lecithins tested. SLP-WHITE liposomes were then prepared by the mechanochemical method using a homogenizer and microfluidizer, aiming at improving the preparation efficiency and liposome stability. The particle size of the prepared SLP-WHITE liposomes decreased with increasing inlet pressure and the number of processed cycles, and reached between 73 and 123 nm based on the measurement using dynamic light scattering. Moreover, freeze-fracture transmission electron microscopy revealed that the prepared liposomes are small unilamellar vesicles (SUV) with a diameter of approximately 100 nm. The extract of Curcuma longa Linn. (Ukon), which contains curcumins as a functional food material, was then subjected to the mechanochemical method with SLP-WHITE to give liposomes including the functional materials. Interestingly, the trapping efficiency of the liposomes for curcumins was found to reach over 85%. From these results, the present mechanochemical method is very likely to allow us to efficiently prepare stable and functional liposomes from the low-cost lecithin. The method may thus have a potential for manufacturing practical nanocapsules, which serves as a novel carrier of functional food materials.

  Influence of tetrahydrocurcumin on erythrocyte membrane bound enzymes and antioxidant status in experimental type 2 diabetic rats.:J Ethnopharmacol. 2007 Jul 10;

 Curcuma longa (Zingiberaceae) has been used traditionally as antidiabetic and has been proven scientifically to possess high antioxidant activity and anticancer properties. The active components of Curcuma longa such as curcumin and tetrahydrocurcumin (THC), a major colourless metabolite of curcumin also possesses antidiabetic, antiinflammatory and antioxidant activity. In the present study the effect of THC and curcumin on erythrocyte membrane bound enzymes and antioxidants activity in streptozotocin (STZ) and nicotinamide induced type 2 diabetic model was investigated. Oral administration of THC at 80mg/kg body weight to diabetic rats for 45 days. The effect of THC and curcumin on glucose, insulin, haemoglobin, glycosylated haemoglobin, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), glutathione-S-transferase (GST), reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of THC was compared with curcumin. The levels of blood glucose, glycosylated haemoglobin, erythrocyte TBARS, were increased significantly whereas the level of plasma insulin and haemoglobin, erythrocyte antioxidants (SOD, CAT, GPx, GST and GSH), membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase were decreased significantly in diabetic rats. Administration of THC and curcumin to diabetic rats showed decreased level of blood glucose, glycosylated haemoglobin and erythrocyte TBARS. In addition the levels of plasma insulin, haemoglobin, erythrocyte antioxidants and the activities of membrane bound enzymes also were increased in THC and curcumin treated diabetic rats. These biochemical observations were supplemented by histopathological examination of pancreas section. The present study indicates that the THC possesses a significant beneficial effect on erythrocyte membrane bound enzymes and antioxidants defense in addition to its antidiabetic effect.

  Chromosome numbers and genome size variation in Indian species of curcuma (zingiberaceae).:Ann Bot (Lond). 2007 Sep;100(3):505-26. Epub 2007 Aug 8.Leong-Skornickov¨¢ J, S¨ªda O, Jarol¨ªmov¨¢ V, Sabu M, F¨¦r T, Tr¨¢vn¨ªcek P, Suda J.Department of Botany, Charles University in Prague, Ben¨¢tsk¨¢ 2, Prague 2, CZ-128 01, Czech Republic.

 Background and Aims Genome size and chromosome numbers are important cytological characters that significantly influence various organismal traits. However, geographical representation of these data is seriously unbalanced, with tropical and subtropical regions being largely neglected. In the present study, an investigation was made of chromosomal and genome size variation in the majority of Curcuma species from the Indian subcontinent, and an assessment was made of the value of these data for taxonomic purposes. Methods Genome size of 161 homogeneously cultivated plant samples classified into 51 taxonomic entities was determined by propidium iodide flow cytometry. Chromosome numbers were counted in actively growing root tips using conventional rapid squash techniques. Key Results Six different chromosome counts (2n = 22, 42, 63, >70, 77 and 105) were found, the last two representing new generic records. The 2C-values varied from 1.66 pg in C. vamana to 4.76 pg in C. oligantha, representing a 2.87-fold range. Three groups of taxa with significantly different homoploid genome sizes (Cx-values) and distinct geographical distribution were identified. Five species exhibited intraspecific variation in nuclear DNA content, reaching up to 15.1 % in cultivated C. longa. Chromosome counts and genome sizes of three Curcuma-like species (Hitchenia caulina, Kaempferia scaposa and Paracautleya bhatii) corresponded well with typical hexaploid (2n = 6x = 42) Curcuma spp. Conclusions The basic chromosome number in the majority of Indian taxa (belonging to subgenus Curcuma) is x = 7; published counts correspond to 6x, 9x, 11x, 12x and 15x ploidy levels. Only a few species-specific C-values were found, but karyological and/or flow cytometric data may support taxonomic decisions in some species alliances with morphological similarities. Close evolutionary relationships among some cytotypes are suggested based on the similarity in homoploid genome sizes and geographical grouping. A new species combination, Curcuma scaposa (Nimmo) Skornick. & M. Sabu, comb. nov., is proposed.

  A pilot and feasibility study on the effects of naturopathic botanical and dietary interventions on sex steroid hormone metabolism in premenopausal women.:Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1601-9.Greenlee H, Atkinson C, Stanczyk FZ, Lampe JW.Mailman School of Public Health, Columbia University, 7th Floor, 722 West 168th Street, New York, NY 10028, USA. hg2120@columbia.edu

 Naturopathic physicians commonly make dietary and/or dietary supplement recommendations for breast cancer prevention. This placebo-controlled, parallel-arm, pilot study tested the effects of two naturopathic interventions over five menstrual cycles on sex steroid hormones and metabolic markers in 40 healthy premenopausal women. The intervention arms were as follows: combination botanical supplement (Curcuma longa, Cynara scolymus, Rosmarinus officinalis, Schisandra chinensis, Silybum marinum, and Taraxacum officinalis; n = 15), dietary changes (3 servings/d crucifers or dark leafy greens, 30 g/d fiber, 1-2 liters/d water, and limiting caffeine and alcohol consumption to 1 serving each/wk; n = 10), and placebo (n = 15). Early-and late-follicular phase serum samples from cycles 1 and 5 were analyzed for estrogens (estrone, estrone-sulfate, total estradiol, and free estradiol), androgens (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and free testosterone), sex hormone-binding globulin, and metabolic markers (insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and leptin). Serum samples collected during the mid-luteal phase of cycles 1 and 5 were analyzed for total estradiol, free estradiol, and sex hormone-binding globulin. Urine samples collected during the late follicular phase of cycles 1 and 5 were analyzed for 2-hydroxyestrone and 16alpha-hydroxyestrone. During the early follicular phase, compared with placebo, the botanical supplement decreased dehydroepiandrosterone (-13.2%; P = 0.02), dehydroepiandrosterone-sulfate (-14.6%; P = 0.07), androstenedione (-8.6%; P = 0.05), and estrone-sulfate (-12.0%; P = 0.08). No other trends or statistically significant changes were observed. When comparing dietary changes with placebo, no statistically significant differences were observed. Overall, in this pilot study, the naturopathic interventions had no substantial effects on estrogen measures. Early-follicular phase androgens decreased with the botanical supplement.


  Primary study on rapid propagation of Curcuma xanthorrhiza.:Zhong Yao Cai. 2007 Apr;30(4):383-5. Chinese.L¨¹ P, Wei LJ, Pang XH, Yu BC, Su WP, Ye QT.Biotechnology Center, Gunagxi Institute of Subtropical Crops, Nanning, China. plvgx@126.com

 Using the rhizome of Curcuma xanthorrhiza Roxb. as explant to induce the adventitious bud, multiplication and radication. The results showed that the inducing and differentiating of bud was better on MS + 6-BA 1.0 mg/L + NAA 0.5 mg/L, the multiplication of bud was on MS+6-BA 1.2 mg/L + NAA 0.l mg/L and the redication was on 1/2 MS + NAA 0.5 mg/L.

  Curcumin induces apoptosis and inhibits prostaglandin E2 production in synovial fibroblasts of patients with rheumatoid arthritis.:Int J Mol Med. 2007 Sep;20(3):365-72.

 Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of anti-apoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumin-induced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E2 synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.

  Antihyperglycaemic effect of 'Ilogen-Excel', an ayurvedic herbal formulation in streptozotocin-induced diabetes mellitus.:Acta Pol Pharm. 2007 Jan-Feb;64(1):53-61.Umamaheswari S, Prince PS.Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India-608 002.

 'Ilogen-Excel', an Ayurvedic herbal formulation is composed of eight medicinal plants (Curcuma longa, Strychnos potatorum, Salacia oblonga, Tinospora cordifolia, Vetivelia zizanioides, Coscinium fenestratum, Andrographis paniculata and Mimosa pudica). The present study evaluates the antihyperglycemic effect of 'Ilogen-Excel' in streptozotocin induced diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg/kg body weight). Oral administration of 'Ilogen-Excel' (50 mg/kg and 100 mg/kg) for 60 days resulted in significantly lowered levels of blood glucose and significantly increased levels of plasma insulin, hepatic glycogen and total hemoglobin. 'Ilogen-Excel' administration also decreased the levels of glycosylated hemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and vitamin E in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of 'Ilogen-Excel'. Administration of insulin normalized all the biochemical parameters studied in diabetic rats. The effect at a dose of 100 mg/kg was more pronounced than 50 mg/kg and brought back all the parameters to near normal levels. Thus, our study shows the antihyperglycemic effects of 'Ilogen-Excel' in STZ-induced diabetic rats. Our study also shows that combined therapy is better than individual therapy.

  The detection of antibacterial actions of whole herb tinctures using luminescent Escherichia coli.:Phytother Res. 2007 Jul 27;Watt K, Christofi N, Young R.Pollution Research Unit, Applied Research Centre for Health, Environment and Society (ARCHES).

 Two whole cell Escherichia coli luminescent biosensors were used to determine the antibacterial actions of 16 herbal tinctures. These bioassays can detect genotoxic (strain DPD2794) and general oxidative stress (DE135) events when challenged with antibacterial substances. Many of the herbal tinctures were active against these Gram-negative bacteria, affecting their metabolism without, in some cases, arresting cell growth or causing cell death. Antibacterial activity ranged from undetectable for Curcuma longa, Cinnamomum zeylanicum and Apium graveolens to highly effective against both E. coli strains in the case of Rosmarinus officinalis. Some of the results were unexpected. Althaea officinalis affected microbial metabolism in spite of the lack of literature precedent, and Cinnamomum zeylanicum did not appear to be antimicrobial, as claimed in some literature.It is concluded that studies using luminescent bacterial biosensors can provide important new insights into the potency and modes of the lethal and sub-lethal antibacterial action of whole herbs, and thereby provide crucial evidence for efficacy demanded by modern science and medicine.

  Study on effect of different extracts in curcuma long on stability of curcumin.:Zhongguo Zhong Yao Za Zhi. 2007 May;32(10):915-7. Chinese.Han G, Liu ZM, Wang XY, Wang YN. Pharmaceutical Department, North China Coal Medical College, Tangshan Key Laboratory of New Drug Research, Tangshan 063000, China. tsyxhg@163.com

 OBJECTIVE: To investigate effects of different extracted fractions from Curcumia long on the stability of curcumin. There are some constituents that can stabilize curcumin. METHOD: To add the extracts obtained from C. long were water, alcohol, acetone, ether, ethyl acetate, petroleum ether to pure solution of curcumin. To determine the change of curcumin by high performance liquid chromatography (HPLC). To investigate the dynamics of curcumin degradation. RESULT: The stability obtained from alcohol, acetone, ether, ethyl ether all improved the stabilization of curcumin. 80% Alcohol extract had the optimal stabilizineg ability for curcumin. CONCLUSION: The extracts from alcohol are more stable than pure curcumin at same conditions. The stability of curcumin is improved by alcohol extracts.


  Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.:Brain Res. 2007 Aug 8;1162:9-18. Epub 2007 Jun 21.Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, Ogle WO.Department of Biomedical Engineering, University of Florida, Gainesville, FL, 32611, USA.

 Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicine, which has been used to effectively manage stress and depression-related disorders in China. As the active component of curcuma longa, curcumin possesses many therapeutic properties; we have previously described its antidepressant activity in our earlier studies using the chronic unpredictable stress model of depression in rats. Recent studies show that stress-induced damage to hippocampal neurons may contribute to the phathophysiology of depression. The aim of this study was to investigate the effects of curcumin on hippocampal neurogenesis in chronically stressed rats. We used an unpredictable chronic stress paradigm (20 days) to determine whether chronic curcumin treatment with the effective doses for behavioral responses (5, 10 and 20 mg/kg, p.o.), could alleviate or reverse the effects of stress on adult hippocampal neurogenesis. Our results suggested that curcumin administration (10 and 20 mg/kg, p.o.) increased hippocampal neurogenesis in chronically stressed rats, similar to classic antidepressant imipramine treatment (10 mg/kg, i.p.). Our results further demonstrated that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. In addition, curcumin significantly prevented the stress-induced decrease in 5-HT(1A) mRNA and BDNF protein levels in the hippocampal subfields, two molecules involved in hippocampal neurogenesis. These results raise the possibility that increased cell proliferation and neuronal populations may be a mechanism by which curcumin treatment overcomes the stress-induced behavioral abnormalities and hippocampal neuronal damage. Moreover, curcumin treatment, via up-regulation of 5-HT(1A) receptors and BDNF, may reverse or protect hippocampal neurons from further damage in response to chronic stress, which may underlie the therapeutic actions of curcumin.

  Antioxidant potential of fluoxetine in comparison to Curcuma longa in restraint-stressed rats.:Eur J Pharmacol. 2007 Jun 13;Zafir A, Banu N.

 Stress plays a potential role in the onset and exacerbation of depression. Chronic restraint stress in rats, and psychosocial stress in humans, is implicated in the pathophysiology of mood and anxiety disorders. Oxidative damage is an established outcome of restraint stress, which has been suggested to induce many damaging processes contributing to the pathology of stress-induced depression. However, the modulatory role of clinically effective antidepressants, such as fluoxetine, in attenuating oxidative stress has not been well characterized. Therefore, the current study was designed to investigate the antioxidant effects of chronic treatment with fluoxetine in animals submitted to restraint stress. The antioxidant potential of the antidepressant fluoxetine was compared with that of turmeric, used as a standard since it integrates both antioxidant and antidepressant properties. Chronic fluoxetine administration to stressed animals for 21 days prevented restraint stress-induced oxidative damage with an efficacy similar to that of turmeric, as evidenced by significant enhancement of key endogenous antioxidant defense components, comprising the free-radical scavenging enzymes, superoxide:superoxide oxidoreductase (EC 1.15.1.1), hydrogen-peroxide:hydrogen-peroxide oxidoreductase (EC 1.11.1.6), glutathione S-transferase (EC 2.5.1.18) and glutathione:NADP(+)oxidoreductase (EC 1.8.1.7), as well as non-enzymatic antioxidants, GSH, glucose and uric acid, which were severely depleted by restraint stress in animals receiving no treatment. Oxidative stress markers, (S)-lactate:NAD(+) oxidoreductase activity (EC 1.1.1.27), malondialdehyde levels (lipid peroxidation product) and protein carbonyl content were also significantly decreased following fluoxetine treatment. Both these drugs when given alone to non-stressed animals did not alter basal levels of antioxidant defense components and oxidative stress markers significantly. Our findings suggest that the therapeutic efficacy of fluoxetine may be mediated, at least partially, via reversal of oxidative damage as demonstrated by protective enhancement of antioxidant status following a stress-induced decline. In addition, this study demonstrates important implications for pharmacological interventions targeting cellular antioxidants as a promising strategy for protecting against oxidative insults in stress-induced depression.

  A randomized, placebo-controlled, double-blind clinical trial of curcuminoids in oral lichen planus.:Phytomedicine. 2007 Aug;14(7-8):437-46. Epub 2007 Jul 2.Chainani-Wu N, Silverman S Jr, Reingold A, Bostrom A, Mc Culloch C, Lozada-Nur F, Weintraub J.Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143-0658, USA. nita.wu@ucsf.edu

 We studied the efficacy of curcuminoids in the treatment of oral lichen planus (OLP), a chronic, mucocutaneous, immunological disease. Curcuminoids are components of turmeric (Curcuma longa) that have anti-inflammatory activity. Turmeric has been used in Ayurveda (Indian traditional medicine) for centuries. A randomized, double-blind, placebo-controlled trial was conducted. In all, 100 consecutive, eligible patients with OLP presenting to the oral medicine clinic at the University of California, San Francisco, were to be selected. Two interim analyses were to be conducted during the trial. The trial was conducted between February 2003 and September 2004. The first interim analysis was conducted in October 2004 using data from the first 33 subjects. Study subjects were randomized to receive either placebo or curcuminoids at 2000 mg/day for 7 weeks. In addition, all subjects received prednisone at 60 mg/day for the first 1 week. The primary outcome was a change in symptoms from baseline. Secondary outcomes were changes in clinical signs and occurrence of side effects. The first interim analysis did not show a significant difference between the placebo and curcuminoids groups. Conditional power calculations suggested a less than 2% chance that the curcuminoids group would have a significantly better outcome as compared with the placebo group if the trial were continued to completion. Therefore, the study was ended early for futility. Reaching a conclusion regarding the efficacy of curcuminoids based on the results of this study is not possible as it was ended early for futility. Curcuminoids at this dose were well tolerated and the results suggest that for future studies a larger sample size, a higher dose and/or longer duration of curcuminoids administration should be considered; however, for the next step, an RCT of a shorter duration, using a higher dose of curcuminoids, and without an initial course of prednisone, should be considered.

  Standardization and stability studies of neuroprotective lipid soluble fraction obtained from Curcuma longa.:J Pharm Biomed Anal. 2007 Sep 3;44(5):1079-86. Epub 2007 May 13.Watt K, Christofi N, Young R.Pollution Research Unit, Applied Research Centre for Health, Environment and Society (ARCHES).

 Two whole cell Escherichia coli luminescent biosensors were used to determine the antibacterial actions of 16 herbal tinctures. These bioassays can detect genotoxic (strain DPD2794) and general oxidative stress (DE135) events when challenged with antibacterial substances. Many of the herbal tinctures were active against these Gram-negative bacteria, affecting their metabolism without, in some cases, arresting cell growth or causing cell death. Antibacterial activity ranged from undetectable for Curcuma longa, Cinnamomum zeylanicum and Apium graveolens to highly effective against both E. coli strains in the case of Rosmarinus officinalis. Some of the results were unexpected. Althaea officinalis affected microbial metabolism in spite of the lack of literature precedent, and Cinnamomum zeylanicum did not appear to be antimicrobial, as claimed in some literature.It is concluded that studies using luminescent bacterial biosensors can provide important new insights into the potency and modes of the lethal and sub-lethal antibacterial action of whole herbs, and thereby provide crucial evidence for efficacy demanded by modern science and medicine.

  Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs.:World J Gastroenterol. 2007 Jun 21;13(23):3199-205.Adhvaryu MR, Reddy N, Parabia MH.Bapalal Vaidya Botanical Research Centre, Department of Biosciences, Veer Narmad South Gujarat University, 110, Nehru Nagar Society, Ichchhanath Road, Surat 395007, India. adhvaryumeghna@hotmail.com

 AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression induced by Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA). METHODS: Duncan Hartley guinea pigs, weighing 700-1050 g, were treated orally with 50 mg/kg of INH, 100 mg/kg of RIF and 300 mg/kg of PZA for 21-d. 200 mg/kg (bw) of each herb crude extract was administered to the herb control group and 2-h previous to INH+RIF+PZA (AKT) doses to the Herb+AKT groups. Serum alanine aminotransferase (ALT), aspertate aminotransferase (AST) bilirubin and Alkaline Phosphatase (ALP) were assessed on d 0 and 21 in all the groups. Phagocytic % (P%), Phagocytic Index (PI) and Chemotactic Index (CI) were also measured as immunologic parameters. Histological analysis was carried out to assess injury to the liver. RESULTS: The AKT treated control group showed hepatotoxicity as judged by elevated serum AST 5-fold, AST/ALT ratio 4-fold, ALP 2-fold and hepatological changes, such as focal necrosis, portal triaditis and steatosis. Immune function was suppressed as judged by decreased P% (51.67+/-1.68 vs 40.61+/-1.28, P<0.01), PI (2.0725+/-0.05 vs 0.61+/-0.05, P<0.001) and CI (1.8525+/-0.04 vs 0.695+/-0.07, P<0.001). All four herb treated groups showed normal liver histology, enzyme levels and increased P%, while PI and CI were enhanced in the TC and ZM treated groups, respectively. CL+AKT, TC+AKT and ZM+AKT showed nearly normal histology with minimal inflammation and microvesicular steatosis, while OS+AKT showed partial protection. Hepatotoxicity was prevented by restricting the rise of AST by 2-fold in CL+AKT and TC+AKT groups and by 3-fold in OS+AKT and ZM+AKT groups, AST/ALT by 2-fold and ALP to normal levels in all four groups. All four herb+AKT groups showed normal to enhanced neutrophil function. CONCLUSION: All four herbs showed hepatoprotective potential and prevented immunosuppression. CL and TC showed the highest hepatoprotective activity, while TC and ZM showed strong immunostimulatory activity.


  Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 2.:Curr Oncol. 2006 Jun;13(3):99-107.Sagar SM, Yance D, Wong RK.Juravinski Cancer Centre and McMaster University (Department of Medicine), Hamilton, Ontario.

 The herbalist has access to hundreds of years of observational data on the anticancer activity of many herbs. Laboratory studies are expanding the clinical knowledge that is already documented in traditional texts. The herbs that are traditionally used for anti-cancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclo-oxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose-response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or as adaptogens, potentially enhancing the efficacy of the conventional therapies or reducing toxicity. Their effectiveness may be increased when multiple agents are used in optimal combinations. New designs for trials to demonstrate activity in human subjects are required. Although controlled trials may be preferable, smaller studies with appropriate endpoints and surrogate markers for anti-angiogenic response could help to prioritize agents for larger, resource-intensive phase iii trials.

  Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 1.:Curr Oncol. 2006 Feb;13(1):14-26.Sagar SM, Yance D, Wong RK.Juravinski Cancer Centre and McMaster University (Department of Medicine), Hamilton, Ontario.

 An integrative approach for managing a patient with cancer should target the multiple biochemical and physiologic pathways that support tumour development and minimize normal-tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The present article focuses on products that have a high degree of anti-angiogenic activity, but it also describes some of the many other actions of these agents that can inhibit tumour progression and reduce the risk of metastasis. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclooxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. The herbs that are traditionally used for anticancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose-response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or as adaptogens, potentially enhancing the efficacy of the conventional therapies.

  Curcumin and autoimmune disease.:Adv Exp Med Biol. 2007;595:425-51. Review.Bright JJ.Neuroscience Research Laboratory, Methodist Research Institute, Clarian Health, Indianapolis, IN 46202, USA. jbright1@clarian.org

 The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

   Protection from acute and chronic lung diseases by curcumin.:Adv Exp Med Biol. 2007;595:379-405. Review.Venkatesan N, Punithavathi D, Babu M.Faculte de Medecine, UMR-7561, CNRS UHP, Vandoeuvre l¨¨s Nancy, France. vnar12@yahoo.com

 The aim of this review has been to describe the current state of the therapeutic potential of curcumin in acute and chronic lung injuries. Occupational and environmental exposures to mineral dusts, airborne pollutants, cigarette smoke, chemotherapy, and radiotherapy injure the lungs, resulting in acute and chronic inflammatory lung diseases. Despite major advances in treating lung diseases, until now disease-modifying efficacy has not been demonstrated for any of the existing drugs. Current medical therapy offers only marginal benefit; therefore, there is an essential need to develop new drugs that might be of effective benefit in clinical settings. Over the years, there has been increasing evidence that curcumin, a phytochemical present in turmeric (Curcuma longa), has a wide spectrum of therapeutic properties and a remarkable range of protective effects in various diseases. Several experimental animal models have tested curcumin on lung fibrosis and these studies demonstrate that curcumin attenuates lung injury and fibrosis caused by radiation, chemotherapeutic drugs, and toxicants. The growing amount of data from pharmacological and animal studies also supports the notion that curcumin plays a protective role in chronic obstructive pulmonary disease, acute lung injury, acute respiratory distress syndrome, and allergic asthma, its therapeutic action being on the prevention or modulation of inflammation and oxidative stress. These findings give substance to the possibility of testing curcumin in patients with lung diseases.

  Cardioprotective effects of curcumin.:Adv Exp Med Biol. 2007;595:359-77. Review.Miriyala S, Panchatcharam M, Rengarajulu P.Department of Medicine, Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill 27599, USA. sumishree@hotmail.com

 Curcumin, a major active component of turmeric, is extracted from the powdered dry rhizome of Curcuma longa Linn (Zingiberaceae) and it has been used for centuries in indigenous medicine. We have shown that curcumin has a protective role against myocardial necrosis in rats. The antioxidant activity of curcumin could be attributed to the phenolic and methoxy groups in conjunction with the 1,3-diketone-conjugated diene system, for scavenging of the oxygen radicals. In addition, curcumin is shown to enhance the activities of detoxifying enzymes such as glutathione-S-transferase in vivo. We have also shown that oxygen free radicals exacerbate cardiac damage and curcumin induces cardioprotective effect and it also inhibits free-radical generation in myocardial ischemia in rats. This chapter on the cardioprotective effects of curcumin covers the following aspects: (1) the history of curcumin and its discovery as a potent drug with relevance to cardiovascular diseases; (2) mechanistic role of curcumin in vitro, emphasizing the antiplatelet and anticoagulant effects; (3) cardiovascular properties of curcumin; (4) application of curcumin in different animal models (viz. myocardial ischemia, myocardial infarction, cardiomyopathy, and arrhythmia in vitro and in vivo); (5) curcumin free-radical scavenging activity, particularly against O2 radical and depletion of the oxidative stress.


  Immunomodulation by curcumin.:Adv Exp Med Biol. 2007;595:321-41. Review.Gautam SC, Gao X, Dulchavsky S.Department of Surgery, Henry Ford Health System, Detroit, MI 48202, USA. sgautam1@hfhs.org

 Turmeric, the bright yellow spice extracted from the tuberous rhizome of the plant Curcuma longa, has been used in traditional Indian and Chinese systems of medicine for centuries to treat a variety of ailments, including jaundice and hepatic disorders, rheumatism, anorexia, diabetic wounds, and menstrual difficulties. Most of the medicinal effects of turmeric have been attributed to curcumin, the principal curcumanoid found in turmeric. Recent evidence that curcumin exhibits strong anti-inflammatory and antioxidant activities and modulates the expression of transcription factors, cell cycle proteins, and signal transducing kinases has prompted the mechanism-based studies on the potential of curcumin to primarily prevent and treat cancer and inflammatory diseases. Little work has been done to study the effect of curcumin on the development of immune responses. This review discusses current knowledge on the immunomodulatory effects of curcumin on various facets of the immune response, including its effect on lymphoid cell populations, antigen presentation, humoral and cell-mediated immunity, and cytokine production.

  Regulation of COX and LOX by curcumin.:Adv Exp Med Biol. 2007;595:213-26. Review.Rao CV.Hematology-Oncology Section, University of Oklahoma Cancer Institute, Oklahoma City 73104, USA. cv-rao@ouhsc.edu

 Turmeric (Curcuma longa) is extensively used as a household remedy for various diseases. For the last few decades, work has been done to establish the biological activities and pharmacological actions of curcumin, the principle constituent of turmeric. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases due to its anti-inflammatory activity. Arachidonic acid-derived lipid mediators that are intimately involved in inflammation are biosynthesized by pathways dependent on cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. The role of LOX and COX isoforms, particularly COX-2, in the inflammation has been well established. At cellular and molecular levels, curcumin has been shown to regulate a number of signaling pathways, including the eicosanoid pathway involving COX and LOX. A number of studies have been conducted that support curcumin-mediated regulation of COX and LOX pathways, which is an important mechanism by which curcumin prevents a number of disease processes, including the cancer. The specific regulation of 5-LOX and COX-2 by curcumin is not fully established; however, existing evidence indicates that curcumin regulates LOX and COX-2 predominately at the transcriptional level and, to a certain extent, the posttranslational level. Thus, the curcumin-selective transcriptional regulatory action of COX-2, and dual COX/LOX inhibitory potential of this naturally occurring agent provides distinctive advantages over synthetic COX/LOX inhibitors, such as nonsteroidal anti-inflammatory drugs. In this review, we discuss evidence that supports the regulation of COX and LOX enzymes by curcumin as the key mechanism for its beneficial effects in preventing various inflammatory diseases.

  Cancer chemopreventive effects of curcumin.:Adv Exp Med Biol. 2007;595:149-72. Review.Surh YJ, Chun KS.National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, South Korea. surh@plaza.snu.ac.kr

 Chemoprevention, which is referred to as the use of nontoxic natural or synthetic chemicals to intervene in multistage carcinogenesis, has emerged as a promising and pragmatic medical approach to reduce the risk of cancer. Numerous components of edible plants, collectively termed "phytochemicals" have been reported to possess substantial chemopreventive properties. Curcumin, a yellow coloring ingredient derived from Curcuma longa L. (Zingiberaceae), is one of the most extensively investigated and well-defined chemopreventive phytochemicals. Curcumin has been shown to protect against skin, oral, intestinal, and colon carcinogenesis and also to suppress angiogenesis and metastasis in a variety animal tumor models. It also inhibits the proliferation of cancer cells by arresting them in the various phases of the cell cycle and by inducing apoptosis. Moreover, curcumin has a capability to inhibit carcinogen bioactivation via suppression of specific cytochrome P450 isozymes, as well as to induce the activity or expression of phase II carcinogen detoxifying enzymes. Well-designed intervention studies are necessary to assess the chemopreventive efficacy of curcumin in normal individuals as well as high-risk groups. Sufficient data from pharmacodynamic as well as mechanistic studies are necessary to advocate clinical evaluation of curcumin for its chemopreventive potential.

  Antioxidant and anti-inflammatory properties of curcumin.:Adv Exp Med Biol. 2007;595:105-25. Review.Menon VP, Sudheer AR.Department of Biochemistry & Center for Micronutrient Research, Annamalai University, Tamilnadu, India. biocmr@sify.com

 Curcumin, a yellow pigment from Curcuma longa, is a major component of turmeric and is commonly used as a spice and food-coloring agent. It is also used as a cosmetic and in some medical preparations. The desirable preventive or putative therapeutic properties of curcumin have also been considered to be associated with its antioxidant and anti-inflammatory properties. Because free-radical-mediated peroxidation of membrane lipids and oxidative damage of DNA and proteins are believed to be associated with a variety of chronic pathological complications such as cancer, atherosclerosis, and neurodegenerative diseases, curcumin is thought to play a vital role against these pathological conditions. The anti-inflammatory effect of curcumin is most likely mediated through its ability to inhibit cyclooxygenase-2 (COX-2), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS). COX-2, LOX, and iNOS are important enzymes that mediate inflammatory processes. Improper upregulation of COX-2 and/or iNOS has been associated with the pathophysiology of certain types of human cancer as well as inflammatory disorders. Because inflammation is closely linked to tumor promotion, curcumin with its potent anti-inflammatory property is anticipated to exert chemopreventive effects on carcinogenesis. Hence, the past few decades have witnessed intense research devoted to the antioxidant and anti-inflammatory properties of curcumin. In this review, we describe both antioxidant and anti-inflammatory properties of curcumin, the mode of action of curcumin, and its therapeutic usage against different pathological conditions.

  Curcumin: the Indian solid gold.:Adv Exp Med Biol. 2007;595:1-75. Review.Aggarwal BB, Sundaram C, Malani N, Ichikawa H.Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. aggarwal@mdanderson.org

 Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".


  Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies.:Evid Based Complement Alternat Med. 2007 Jun;4(2):181-190. Epub 2007 Apr 23.Salvioli S, Sikora E, Cooper EL, Franceschi C.Department of Experimental Pathology and Centro Interdipartimentale ¡°L. Galvani¡±, University of Bologna, via S. Giacomo 12, 40126 Bologna, Italy, ER-GenTech laboratory, via Saragat 1, 44100 Ferrara, Italy, Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteura St., 02-093 Warsaw, Poland, Laboratory of Comparative Neuroimmunology, Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles California 90095-1763 and I.N.R.C.A., Department of Gerontological Sciences, via Birarelli 8, 60121 Ancona, Italy

 Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.

  New sesquiterpenes and calebin derivatives from Curcuma longa.:Chem Pharm Bull. 2007 Jun;55(6):940-3.Zeng Y, Qiu F, Takahashi K, Liang J, Qu G, Yao X.Department of Natural Products Chemistry 81#, Shenyang Pharmaceutical University, Shenyang, PR China.

 One novel sesquiterpene with new skeleton, (6S)-2-methyl-6-(4-hydroxyphenyl-3-methyl)-2-hepten-4-one (1), two new bisabolane sesquiterpenes, (6S)-2-methyl-6-(4-hydroxyphenyl)-2-hepten-4-one (2), (6S)-2-methyl-6-(4-formylphenyl)-2-hepten-4-one (3), and two calebin derivatives, 4''-(4'''-hydroxyphenyl-3'''-methoxy)-2''-oxo-3''-butenyl-3-(4'-hydroxyphenyl)-propenoate (4) and 4''-(4'''-hydroxyphenyl)-2''-oxo-3''-butenyl-3-(4'-hydroxyphenyl-3'-methoxy)-propenoate (5) were isolated along with five known bisabolane sesquiterpenes from Curcuma longa. 1-4 were new compounds and 5 was a new natural product. Their structures were established by spectral methods.

  Dietary curcumin does not protect kidney in glycerol-induced acute renal failure.:Food Chem Toxicol. 2007 Sep;45(9):1777-1782. Epub 2007 Apr 20.Vlahovi? P, Cvetkovi? T, Savi? V, Stefanovi? V.Institute of Nephrology and Hemodialysis, Clinical Center Ni?, Dr Zorana ?in?i?a 48, 18000 Ni?, Serbia.

 Generation of reactive oxygen species significantly contribute to the pathogenesis of renal injury induced by myoglobin release. The present study was performed to investigate the effects of dietary curcumin, a natural antioxidant isolated from plant Curcuma longa, in an experimental model of myoglobinuric acute renal failure. Rats received curcumin at an oral dose of 100mg/kg/day for 30days. Renal injury was induced with injection of hypertonic glycerol (10ml/kg 50% solution) in hind limb muscle with blood urea of 57.8+/-7.2 vs. 7.72+/-1.03mmol/l and serum creatinine of 444.4+/-61.3 vs. 51.8+/-10.6mumol/l, in glycerol-induced acute renal failure (ARF) vs. control rats, respectively. After 48h rats were sacrificed and thiobarbituric acid reactive substance (TBARS), glutathione, carbonyl content and kidney cortex brush border peptidase activities were determined in serum, kidney and liver. Rats that received curcumin in addition to glycerol had significantly lower TBARS in serum but not in kidney and liver. Carbonyl content in kidney and liver was significantly elevated in curcumin and glycerol treated rats and improved in animals treated with curcumin and glycerol together. The activities of kidney cortex enzymes, aminopeptidase N, angiotensinase A and dipeptidyl peptidase IV, were reduced in glycerol as well as in curcumin treated rats. The results obtained in this study provided additional evidence that despite its limited antioxidant activity curcumin did not protect kidney in myoglobinuric model of ARF.

  Carbohydrate metabolism in Dioscorea esculenta (Lour.) Burk. tubers and Curcuma longa L. rhizomes during two phases of dormancy.:Colloids Surf B Biointerfaces. 2007 Sep 1;59(1):59-66. Epub 2007 Apr 21.Panneerselvam R, Abdul Jaleel C, Somasundaram R, Sridharan R, Gomathinayagam M.Stress Physiology Laboratory, Department of Botany, Annamalai University, Annamalainagar 608002, Tamil Nadu, India. rpselvam9@hoptmail.com

 We have examined the changes in carbohydrate metabolism in food yam (Dioscorea esculenta (Lour.) Burk.) tubers and in an economically important spice cum medicinal plant turmeric (Curcuma longa L.) rhizomes under storage. Both specimens showed varied levels of dormancy and sprouting appeared at the end of dormant period. Harvested, fully matured tubers of yam and rhizomes of turmeric were stored in wooden boxes under the conditions of 28+/-2 degrees C temperature and 65-75% relative humidity (RH) in dark. The starch, sugars, enzymes of starch degradation, respiration, glycolysis, tricarboxylic acid (TCA) cycle and oxidative pentose phosphate pathway (PPP) were studied during 1-70 days after harvest (DAH). This investigation revealed that, the starch degradation and the enzymes involved, viz. alpha-amylases and starch phosphorylase showed a lower level of activity during early period of dormancy, while sugar content and enzymes of carbohydrate metabolism increased rapidly during sprouting. The isoenzymic profiles of alpha-amylases showed marked variations in these two phases. The key enzymes of glycolysis, TCA cycle and PPP, viz. aldolase, succinic dehydrogenase, malic dehydrogenase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were increased even before the visible appearance of sprouting and their activities were at their maximum during sprouting. Based of the observations the dormancy period may be distinctly divided into peak period of rest and presprouting period.

  Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism.:Carcinogenesis. 2007 Aug;28(8):1765-73. Epub 2007 May 23.Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, Limtrakul P, Badmaev V, Aggarwal BB.Cytokine Research Section, Department of Experimental Therapeutics, Box 143, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

 Curcumin, a component of turmeric (Curcuma longa), has been shown to exhibit chemopreventive activity. Whether analogs of curcumin (Cur), such as demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), tetrahydrocurcumin (THC) and turmerones, modulate inflammatory signaling and cell proliferation signaling to same extent as curcumin was investigated. The results indicate that the relative potency for suppression of tumor necrosis factor (TNF)-induced nuclear factor-kappaB (NF-kappaB) activation was Cur > DMC > BDMC; thus suggesting the critical role of methoxy groups on the phenyl ring. THC, which lacks the conjugated bonds in the central seven-carbon chain, was completely inactive for suppression of the transcription factor. Turmerones also failed to inhibit TNF-induced NF-kappaB activation. The suppression of NF-kappaB activity correlated with inhibition of NF-kappaB reporter activity and with down-regulation of cyclooxygenase-2, cyclin D1 and vascular endothelial growth factor, all regulated by NF-kappaB. In contrast to NF-kappaB activity, the suppression of proliferation of various tumor cell lines by Cur, DMC and BDMC was found to be comparable; indicating the methoxy groups play minimum role in the growth-modulatory effects of curcumin. THC and turmerones were also found to be active in suppression of cell growth but to a much lesser extent than curcumin, DMC and BDMC. Whether suppression of NF-kappaB or cell proliferation, no relationship of any of the curcuminoid was found with reactive oxygen species (ROS) production. Overall, our results demonstrated that different analogs of curcumin present in turmeric exhibit variable anti-inflammatory and anti-proliferative activities, which do not correlate with their ability to modulate the ROS status.


  Potential of plant extracts in combination with bacterial antagonist treatment as biocontrol agent of red rot of sugarcane.:Can J Microbiol. 2007 Feb;53(2):196-206. Jayakumar V, Bhaskaran R, Tsushima S.Department of Plant Pathology, Agricultural College and Research Institute, Tamil Nadu Agricultural University, Madurai 625104, Tamil Nadu, India.

 Plant extracts and antifungal microorganisms were tested singly and in combination for biocontrol of sugarcane red rot disease (Colletotrichum falcatum) using two sugarcane (Saccharum officinarum L.) cultivars, CoC671 and CoC92061, in pot and field experiments. Leaf extracts of Abrus precatorius and Bassia latifolia and the rhizome extract of Curcuma longa reduced Colletotrichum falcatum mycelial growth by 80%, 58%, and 57%, respectively. Although sugarcane- planting materials (setts) treated individually with either Pseudomonas fluorescens Md1 or A. precatorius in pot experiments had the lowest incidences of red rot, 20.1% and 24.2%, respectively, none of the plant extracts were effective in the field. In contrast, when the two varieties were tested separately in two field locations, the setts treated with A. precatorius in combination with a spray or soil application of P. fluorescens Md1 had the lowest incidence of red rot in both locations, e.g., 3.1% and 3.4% incidence for CoC92061 in one location, and had a similar response to the chemical control. The results suggest the applicability of plant-based extracts for the suppression of sugarcane red rot disease in the field as an environment-friendly tool in combination with antagonists.

  A curcumin-based 1-week triple therapy for eradication of Helicobacter pylori infection: something to learn from failure?:Helicobacter. 2007 Jun;12(3):238-43.Di Mario F, Cavallaro LG, Nouvenne A, Stefani N, Cavestro GM, Iori V, Maino M, Comparato G, Fanigliulo L, Morana E, Pilotto A, Martelli L, Martelli M, Leandro G, Franz¨¨ A.Section of Gastroenterology, Department of Clinical Sciences, University of Parma, Italy. francesco.dimario@unipr.it

 BACKGROUND: Curcumin is the principal element of turmeric powder extracted from the root of Curcuma longa. Studies on curcumin have demonstrated some anti-Helicobacter pylori activity as well as immunomodulating properties. N-acetylcysteine and lactoferrin with their respective mucolytic and antibacterial activities might also be effective in H. pylori eradication therapy. AIM: To determine if a 7-day non-antibiotic therapy comprised of curcumin, lactoferrin, N-acetylcysteine, and pantoprazole was effective for eradication of H. pylori infection and reduction of gastric inflammation, assessed by serum pepsinogens and relief of symptoms. SUBJECTS AND METHODS: Twenty-five consecutive H. pylori-positive patients (12 males, mean age 50 +/- 12 years, range 31-76) with functional dyspepsia were enrolled. Patients were administered for 7 days curcumin 30 mg b.i.d., bovine lactoferrin 100 mg b.i.d., N-acetylcysteine 600 mg b.i.d., and pantoprazole 20 mg b.i.d. H. pylori status and upper gastrointestinal symptoms were assessed by (13)C-urea breath test and a scale of upper gastrointestinal symptoms intensity (absent, mild, moderate, and severe), as well as a blood test for serum pepsinogens (sPGI, sPGII), gastrin-17 (G-17), and anti-H. pylori IgG (IgG-Hp) at baseline (T0) and after 2 months (T1). RESULTS: Three of 25 patients (12%) were cured of H. pylori infection. A significant decrease in the overall severity of symptoms (T0: 6, interquartile range [IQR]: 4.5-8; T1: 2, IQR: 2-3; p < or = .001), and sPGII (T0: 16 microg/L, IQR: 13-22; T1: 10 microg/L, IQR: 8-16; p < or = .001) and sPGI (T0: 82 microg/L, IQR: 67-97; T1: 74 microg/L, IQR: 62-94; p = .02) levels were observed after 2 months of the treatment. IgG and G-17 values did not significantly decrease after 2 months. CONCLUSIONS: This novel therapy was not effective for H. pylori eradication. However, despite the bacterium persistence, significant improvement of dyspeptic symptoms and reduction of serologic signs of gastric inflammation were observed after 2 months at the end of the 7-day treatment schedule.

  The safety and efficacy of a dietary herbal supplement and gallic acid for weight loss.:J Med Food. 2007 Mar;10(1):184-8.Roberts AT, Martin CK, Liu Z, Amen RJ, Woltering EA, Rood JC, Caruso MK, Yu Y, Xie H, Greenway FL.Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.

 The objective of this study was to test the safety and efficacy of NT, a dietary herbal supplement made from rhubarb, ginger, astragulus, red sage, and turmeric, combined with gallic acid (GA) to reduce food intake and cause weight loss. A total of 105 healthy subjects, 18-60 years old with a body mass index of 25-35 kg/m(2) and on no chronic medication, were randomized to a 300 mg/1.2 g NT-GA combination, a 600 mg/2.4 g NT-GA combination, or placebo in three divided doses daily for 24 weeks. Food intake was measured at baseline and 2 weeks, and safety parameters were followed regularly. Pharmacokinetic studies of a 200 mg/800 g NT-GA combination and 800 mg GA alone were performed with and without food. There was no dose-related weight loss or reduction in food intake at the 8-week analysis, and the study was terminated early. Pharmacokinetic studies showed plasma levels of GA did not increase above 10 microM and were not dose-related. The NT-GA at all concentrations was well tolerated, but was ineffective in causing weight loss or in suppressing food intake. Pharmacokinetics suggested that GA plasma levels were limited by oral absorption, and may be the reason for lack of efficacy.

  Curcuma longa extract as a histological dye for collagen fibres and red blood cells.:J Anat. 2007 May;210(5):600-3.Avwioro OG, Onwuka SK, Moody JO, Agbedahunsi JM, Oduola T, Ekpo OE, Oladele AA.Department of Histopathology, School of Medical Laboratory Science, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria. avwiorog@yahoo.com

 Crude ethanolic extract and column chromatographic fractions of the Allepey cultivar of Curcuma longa Roxb, commonly called turmeric (tumeric) in commerce, were used as a stain for tissue sections. Staining was carried out under basic, acidic and neutral media conditions. Inorganic and organic dissolution solvents were used. The stain was used as a counterstain after alum and iron haematoxylins. C. longa stained collagen fibres, cytoplasm, red blood cells and muscle cells yellow. It also stained in a fashion similar to eosin, except for its intense yellow colour. Preliminary phytochemical evaluation of the active column fraction revealed that it contained flavonoids, free anthraquinone and deoxy sugar. A cheap, natural dye can thus be obtained from C. longa.

  Curcumin activates human glutathione S-transferase P1 expression through antioxidant response element.:Toxicol Lett. 2007 May 15;170(3):238-47. Epub 2007 Mar 24.

 Curcumin is a plant-derived diferuloylmethane compound extracted from Curcuma longa, possessing antioxidative and anticarcinogenic properties. Antioxidants and oxidative stress are known to induce the expression of certain classes of detoxification enzymes. Since the upregulation of detoxifying enzymes affects the drug metabolism and cell defense system, it is important to understand the gene regulation by such agents. In this study, we demonstrated that curcumin could induce the expression of human glutathione S-transferase P1 (GSTP1). In HepG2 cells treated with 20muM curcumin, the level of GSTP1 mRNA was significantly increased. In luciferase reporter assays, curcumin augmented the promoter activity of a reporter construct carrying 336bp upstream of the 5'-flanking region of the GSTP1 gene. Mutation analyses revealed that the region including antioxidant response element (ARE), which overlaps AP1 in sequence, was essential to the response to curcumin. While the introduction of a wild-type Nrf2 expression construct augmented the promoter activity of the GSTP1 gene, co-expression of a dominant-negative Nrf2 abolished the responsiveness to curcumin. In addition, curcumin activated the expression of the luciferase gene from a reporter construct carrying multiple ARE consensus sequences but not one with multiple AP1 sites. In a gel mobility shift assay with an oligonucleotide with GSTP1 ARE, an increase in the amount of the binding complex was observed in the nuclear extracts of curcumin-treated HepG2 cells. These results suggested that ARE is the primary sequence for the curcumin-induced transactivation of the GSTP1 gene. The induction of GSTP1 may be one of the mechanisms underlying the multiple actions of curcumin.


  Curcumin for chemoprevention of colon cancer.:Cancer Lett. 2007 Oct 8;255(2):170-81. Epub 2007 Apr 19.Johnson JJ, Mukhtar H.University of Wisconsin, School of Pharmacy, 777 Highland Avenue, Madison, WI 53705-2222, USA; University of Wisconsin, School of Medicine and Public Health, Department of Dermatology, 1300 University Avenue, Madison, WI 53706, USA.

 The most practical approach to reduce the morbidity and mortality of cancer is to delay the process of carcinogenesis through the use of chemopreventive agents. This necessitates that safer compounds, especially those derived from natural sources must be critically examined for chemoprevention. A spice common to India and the surrounding regions, is turmeric, derived from the rhizome of Curcuma longa. Pre-clinical studies in a variety of cancer cell lines including breast, cervical, colon, gastric, hepatic, leukemia, oral epithelial, ovarian, pancreatic, and prostate have consistently shown that curcumin possesses anti-cancer activity in vitro and in pre-clinical animal models. The robust activity of curcumin in colorectal cancer has led to five phase I clinical trials being completed showing the safety and tolerability of curcumin in colorectal cancer patients. To date clinical trials have not identified a maximum tolerated dose of curcumin in humans with clinical trials using doses up to 8000mg per day. The success of these trials has led to the development of phase II trials that are currently enrolling patients. Overwhelming in vitro evidence and completed clinical trials suggests that curcumin may prove to be useful for the chemoprevention of colon cancer in humans. This review will focus on describing the pre-clinical and clinical evidence of curcumin as a chemopreventive compound in colorectal cancer.

  Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products.:Cancer Res. 2007 Apr 15;67(8):3853-61.Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB.Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

 Gemcitabine is currently the best treatment available for pancreatic cancer, but the disease develops resistance to the drug over time. Agents that can either enhance the effects of gemcitabine or overcome chemoresistance to the drug are needed for the treatment of pancreatic cancer. Curcumin, a component of turmeric (Curcuma longa), is one such agent that has been shown to suppress the transcription factor nuclear factor-kappaB (NF-kappaB), which is implicated in proliferation, survival, angiogenesis, and chemoresistance. In this study, we investigated whether curcumin can sensitize pancreatic cancer to gemcitabine in vitro and in vivo. In vitro, curcumin inhibited the proliferation of various pancreatic cancer cell lines, potentiated the apoptosis induced by gemcitabine, and inhibited constitutive NF-kappaB activation in the cells. In vivo, tumors from nude mice injected with pancreatic cancer cells and treated with a combination of curcumin and gemcitabine showed significant reductions in volume (P = 0.008 versus control; P = 0.036 versus gemcitabine alone), Ki-67 proliferation index (P = 0.030 versus control), NF-kappaB activation, and expression of NF-kappaB-regulated gene products (cyclin D1, c-myc, Bcl-2, Bcl-xL, cellular inhibitor of apoptosis protein-1, cyclooxygenase-2, matrix metalloproteinase, and vascular endothelial growth factor) compared with tumors from control mice treated with olive oil only. The combination treatment was also highly effective in suppressing angiogenesis as indicated by a decrease in CD31(+) microvessel density (P = 0.018 versus control). Overall, our results suggest that curcumin potentiates the antitumor effects of gemcitabine in pancreatic cancer by suppressing proliferation, angiogenesis, NF-kappaB, and NF-kappaB-regulated gene products.

  Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy.:J Nanobiotechnology. 2007 Apr 17;5:3.Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A, Maitra A.The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. sbisht1@jhmi.edu

 BACKGROUND: Curcumin, a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa), has potent anti-cancer properties as demonstrated in a plethora of human cancer cell line and animal carcinogenesis models. Nevertheless, widespread clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media, thus circumventing the pitfalls of poor solubility. RESULTS: We have synthesized polymeric nanoparticle encapsulated formulation of curcumin - nanocurcumin - utilizing the micellar aggregates of cross-linked and random copolymers of N-isopropylacrylamide (NIPAAM), with N-vinyl-2-pyrrolidone (VP) and poly(ethyleneglycol)monoacrylate (PEG-A). Physico-chemical characterization of the polymeric nanoparticles by dynamic laser light scattering and transmission electron microscopy confirms a narrow size distribution in the 50 nm range. Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous media. Nanocurcumin demonstrates comparable in vitro therapeutic efficacy to free curcumin against a panel of human pancreatic cancer cell lines, as assessed by cell viability and clonogenicity assays in soft agar. Further, nanocurcumin's mechanisms of action on pancreatic cancer cells mirror that of free curcumin, including induction of cellular apoptosis, blockade of nuclear factor kappa B (NFkappaB) activation, and downregulation of steady state levels of multiple pro-inflammatory cytokines (IL-6, IL-8, and TNFalpha). CONCLUSION: Nanocurcumin provides an opportunity to expand the clinical repertoire of this efficacious agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo models of cancer and other diseases that might benefit from the effects of curcumin.

  HPLC-photodiode array detection analysis of curcuminoids in Curcuma species indigenous to Indonesia.:Phytochem Anal. 2007 Mar;18(2):118-22.Bos R, Windono T, Woerdenbag HJ, Boersma YL, Koulman A, Kayser O.Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1,9713 AV Groningen, The Netherlands. R.Bos@rug.nl

 An optimized HPLC method with photodiode array detection was developed and applied to analyse the curcuminoids curcumin, demethoxycurcumin, and bis-demethoxycurcumin in rhizomes of Curcuma mangga Val &. v. Zijp, C. heyneana Val. & v. Zijp, C. aeruginosa Roxb. and C. soloensis Val. (Zingiberaceae), indigenous to Indonesia. The method was validated with an isocratic system, a short run time of 10 min and a baseline separation. The curcuminoid content was 0.18-0.47% for C. mangga, 0.98-3.21% for C. heyneana, 0.02-0.03% for C. aeruginosa and 0.40% for C. soloensis.

   In vitro assessment of curcumin against murine neuroblastoma cells.:Neuro Endocrinol Lett. 2007 Apr;28(2):204-12.Vanisree AJ, Ramanan R.Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India. vanielango@yahoo.com

 OBJECTIVE: Neuroblastoma (NB) is a well-known malignant disease in infants, which comprises 10% of childhood malignancies. Despite recent advances in understanding the neuro-oncology, NB still accounts for more death in childhood than any other cancer. Research in childhood tumors should not only be focused on the malignant signatures of cancer cells but also novel drug prototypes using phytochemicals. The present study was aimed to determine the role of curcumin against murine neuroblastoma cell line (N2a). METHODS: The in vitro assessment of curcumin against was made in N2a cell line in a dose-dependent manner (group I (control) and group II - IX (10 microM-80 microM). The efficacy of the drug was evaluated by estimating the levels of protein bound carbohydrates, glycoprotein, genomic DNA, total RNA levels, and inhibition of MMP-9 were studied. The gap junctional communication in the cells was also assessed. RESULTS: The levels of protein bound carbohydrates, DNA, RNA levels, glycoprotein were found to be altered on drug supplementation in NB cells. Inhibition of MMP-9 in curcumin-supplemented N2a cells was revealed by zymographic analysis. Assessment of Lucifer yellow dye uptake in curcumin-supplemented N2a cells showed the up-regulation of GJIC. CONCLUSIONS: These observations suggest that the curcumin, the active principle of curcuma longa, could be developed into an effective chemo preventive and chemotherapeutic agent. This selected concentration range needs further studies at molecular level, for conforming its role and its action against uncontrolled proliferation of NB.


  Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products.:Toxicology. 2007 Jun 3;235(1-2):83-91. Epub 2007 Mar 15.Appiah-Opong R, Commandeur JN, van Vugt-Lussenburg B, Vermeulen NP.Division of Molecular Toxicology, Leiden/Amsterdam Center for Drug Research (LACDR), Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.

 Curcumin (diferuloylmethane) is a major yellow pigment and dietary component derived from Curcuma longa. It has potent anti-inflammatory, anticarcinogenic, antioxidant and chemoprotective activities among others. We studied the interactions of curcumin, a mixture of its decomposition products, and four of its individually identified decomposition products (vanillin, vanillic acid, ferulic aldehyde and ferulic acid) on five major human drug-metabolizing cytochrome P450s (CYPs). Curcumin inhibited CYP1A2 (IC(50), 40.0 microM), CYP3A4 (IC(50), 16.3 microM), CYP2D6 (IC(50), 50.3 microM), CYP2C9 (IC(50), 4.3 microM) and CYP2B6 (IC(50), 24.5 microM). Curcumin showed a competitive type of inhibition towards CYP1A2, CYP3A4 and CYP2B6, whereas a non-competitive type of inhibition was observed with respect to CYP2D6 and CYP2C9. The inhibitory activity towards CYP3A4, shown by curcumin may have implications for drug-drug interactions in the intestines, in case of high exposure of the intestines to curcumin upon oral administration. In spite of the significant inhibitory activities shown towards the major CYPs in vitro, it remains to be established, whether curcumin will cause significant drug-drug interactions in the liver, given the reported low systemic exposure of the liver to curcumin. The decomposition products of curcumin showed no significant inhibitory activities towards the CYPs investigated, and therefore, are not likely to cause drug-drug interactions at the level of CYPs.

  Curcumin Prevents the Development of Dextran Sulfate Sodium (DSS)-Induced Experimental Colitis.:Dig Dis Sci. 2007 Apr 11;

 Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa (turmeric). We evaluated the effects of curcumin on the development of dextran sulfate sodium (DSS)-induced experimental colitis. BALB/c mice were fed a chow containing either 3.5% (wt/wt) DSS or 3.5% DSS + 2.0% (wt/wt) curcumin. The body weight loss was more apparent in DSS-treated mice than in DSS + curcumin-treated mice. The disease activity index, histological colitis score, and MPO activity were all significantly higher in DSS-treated mice than in DSS plus curcumin-treated mice. Microscopically, mucosal edema, cellular infiltration, and epithelial disruption were much more severe in DSS-treated mice than in DSS + curcumin-treated mice. In DSS + curcumin-treated mice, NF-kappaB activation was blocked in the mucosa. In conclusion, the development of DSS-induced colitis was significantly attenuated by curcumin. Being a nontoxic natural dietary product, curcumin could be useful in treatment of IBD patients.

  Molecular interactions between dimethoxycurcumin and Pamam dendrimer carriers.:Int J Pharm. 2007 Jul 18;339(1-2):231-6. Epub 2007 Mar 12.Markatou E, Gionis V, Chryssikos GD, Hatziantoniou S, Georgopoulos A, Demetzos C.School of Pharmacy Department of Pharmaceutical Technology, Panepistimiopolis Zografou 15771, University of Athens, Athens, Greece.

 Dimethoxycurcumin, a lipophilic analog of curcumin found as a major pigment in the Indian species turmeric (Curcuma longa Linn.), is known to possess significant activity against various cancer cell lines, but its use as an anticancer drug is hindered by its poor water solubility. The conjugation of dimethoxycurcumin to water-soluble PAMAM dendrimers (generations 3.5 and 4) is demonstrated. The maximum drug-dendrimer incorporation efficiency is 4.3 and 5.0 molar for G3.5 and G4, respectively. The FTIR-ATR investigation of the neat compounds and the drug-dendrimer systems indicate that dimethoxycurcumin is in the enolic form, while its interaction with the integer generation dendrimer involves the major conformational change of the terminal ethylene amine groups.

  Total phenol, antioxidant and free radical scavenging activities of some medicinal plants.:Int J Food Sci Nutr. 2007 Feb;58(1):18-28.Prakash D, Suri S, Upadhyay G, Singh BN.Nutraceutical Chemistry, National Botanical Research Institute, Lucknow, India. dprakash_in@yahoo.com

 Phenols, a major group of antioxidant phytochemicals, have profound importance due to their biological and free radical scavenging activities. To identify their potential sources, extracts of some plants were studied for their total phenolic content (TPC), antioxidant (AOA) and free radical scavenging activities (FRSA) by different methods at multiple concentrations followed by specific phenolic composition. The amount of TPC varied from 2.8 mg/g (Withania somnifera, roots) to 107.8 mg/g (Cassia fistula, fruits) and the AOA from 24.2% (Curcuma zeoderia, leaves) to 96.9% (Trewia nudiflora, leaves). Bark of Azadirachta indica, fruits of C. fistula, and leaves and fruits of T. nudiflora were found to have high TPC (89.8- 107.8 mg/g) and high AOA (84.8-96.9%). Promising plant parts were studied for their FRSA and reducing power (RP), where the bark of A. indica, Casuarina equisetifolia and Cinnamomum zeylanicum, flowers of Indigofera tinctoria, fruits of Lawsonia inermis, and fruits and leaves of T. nudiflora showed a very low inhibitory concentration value ranging from 0.14 to 0.26 mg/ml, efficiency concentration value from 6.1 to 11.6 mg/mg DPPH and reducing power value from 0.6 to 2.8 ascorbic acid equivalents (ASE/ml), and reasonably high values (8.5 -16.2) of anti-radical power (ARP), indicating their strong FRSA. They also showed better inhibition of hydroxyl radical induced deoxyribose degradation than that of reference standard. Fruits of C. fistula with high phenols (107.8 mg/g) showed poor reducing power (5.9 ASE/ml) and ARP (4.7); in contrast, the bark of C. equisetifolia and fruits of L. inermis were with comparatively lower phenols (72.1 and 75.8 mg/g) but exhibited good ARP (16.2 and 14.4) and reducing power (0.7 and 0.6 ASE/ ml, respectively). Some of the plants were also found effective in protecting plasmid DNA nicking induced by hydroxyl radicals generated by Fenton's reaction. They were further assayed for their specific phenolic composition through high-performance liquid chromatography and MS/MS, where the amount of caffeic acid varied from 0.312 to 0.797 mg/g, chlorogenic acid from 0.018 to 2.109 mg/g, ellagic acid from 0.009 to 0.902 mg/g, ferulic acid from 0.036 to 0.078 mg/g, gallic acid from 0.192 to 3.597 mg/g, kaempferol from 0.011 to 0.910 mg/g, quercetin from 0.047 to 1.106 mg/g and rutin from 0.059 to 2.029 mg/g.

  Low concentrations of curcumin induce growth arrest and apoptosis in skin keratinocytes only in combination with UVA or visible light.:J Invest Dermatol. 2007 Aug;127(8):1992-2000. Epub 2007 Apr 5.Dujic J, Kippenberger S, Hoffmann S, Ramirez-Bosca A, Miquel J, Diaz-Alperi J, Bereiter-Hahn J, Kaufmann R, Bernd A.Department of Dermatology and Venerology, Medical School, J.W. Goethe-University, Frankfurt/Main, Germany.

 It is well known that curcumin, a dietary pigment from the plant Curcuma longa, inhibits cell proliferation and induces apoptosis in different cell lines at concentrations ranging from 10 to 150 microM (3.7-55 microg/ml). In this study, we show that curcumin at low concentrations (0.2-1 microg/ml) also has an antiproliferative effect when applied in combination with UVA or visible light. We demonstrate that such a treatment induces apoptosis in human skin keratinocytes represented by the increase of fragmented cell nuclei, release of cytochrome c from mitochondria, activation of caspases-9 and -8, and inhibition of NF-kappaB activity. Furthermore, inhibition of extracellular regulated kinases 1/2 and protein kinase B was found to ensure the proapoptotic effect. Additionally, the EGFR, an upstream regulator of both kinases, was inhibited indicating that apoptosis is induced by blocking survival- and proliferation-associated signal cascades at the receptor level. In summary, these findings suggest a new therapeutic concept for the treatment of hyperproliferative diseases by combining topical curcumin with UVA or visible light. In particular, the latter avoids the use of carcinogenic irradiation that is part of regular phototherapy.


  Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS.:J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jun 15;853(1-2):183-9. Epub 2007 Mar 18.Yang KY, Lin LC, Tseng TY, Wang SC, Tsai TH.Institute of Traditional Medicine, National Yang-Ming University, and Ho-Ping Branch, Taipei City Hospital, Taiwan.

 This study presents a validated liquid chromatography technique coupled with tandem mass spectrometry (LC-MS/MS) to measure curcumin in rat plasma and provide curcuminoids analysis from the extract of Curcumin longa L. This method was applied to investigate the pharmacokinetics of curcumin in a freely moving rat. The analytes were separated by a reversed phase C18 column (150x4.6 mm I.D., particle size 5 microm) and eluted with acetonitrile-1mM HCOOH mobile phase (70:30, v/v) with a flow rate of 0.8 ml/min in rat plasma and herbal extracts. Multiple reaction monitoring (MRM) was used to monitor the transition of the deprotonated molecule m/z of 367 [M-H]- to the product ion 217 for curcumin, a m/z of 337-217 for demethoxycurcumin and a m/z of 265-224 for honokiol (internal standard) analysis. The limit of detection (LOD) and quantification (LOQ) of curcumin in the rat plasma were 1 and 5 ng/ml, respectively. The method was linear in the range of 5-1000 ng/ml with a coefficient of correlation greater than 0.996 in the rat plasma. After curcumin (500 mg/kg, p.o.) administration, the maximum concentration (Cmax) and the time to reach maximum concentration (Tmax) were 0.06+/-0.01 microg/ml and 41.7+/-5.4 min, respectively. The elimination half-life (t1/2,beta) were 28.1+/-5.6 and 44.5+/-7.5 min for curcumin (500 mg/kg, p.o.) and curcumin (10 mg/kg, i.v.), respectively. The oral bioavailability was about 1%.

  Curcuma longa as feed additive in broiler birds and its patho-physiological effects.:Indian J Exp Biol. 2007 Mar;45(3):272-7.Kumari P, Gupta MK, Ranjan R, Singh KK, Yadava R.Department of Veterinary Pathology, Ranchi Veterinary College, Birsa Agricultural University, Kanke, Ranchi 834 006, India.

 Broiler birds (Vencob chicken of 3 days old) when given feed mixed with powdered rhizome of Curcuma longa (CL; @ 1 g/kg) for 42 days of age, showed significant decrease in serum uric acid and albumin as compared to control, whereas significant increase was recorded in the level of serum total protein and globulin. Level of serum glucose, alkaline phosphatase, aspartate amino transferase and calcium showed no significant variation between the two groups. Micronutrient assay revealed significantly higher level of manganese, zinc, iron and copper in treated group as compared to control group. HA/HI test revealed better humoral response against RD vaccine in CL administered birds. Haematological study showed significantly higher haemoglobin and absolute neutrophil count in treated group. Addition of CL as feed additive also resulted in better growth rate, feed consumption and F:C efficiency in the treated birds. Thus, it could be concluded that powdered CL might be a useful feed additive, since it enhanced the F:C efficiency and had nephroprotective properties.

  Possible neuroprotective mechanisms of curcumin in attenuating 3-nitropropionic acid-induced neurotoxicity.:Methods Find Exp Clin Pharmacol. 2007 Jan-Feb;29(1):19-25.Kumar P, Padi SS, Naidu PS, Kumar A.Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

 3-Nitropropionic acid (3-NP) is a well known fungic toxin causing neurotoxicity. Systemic administration of 3-NP causes motor and cognitive deficits that are associated with excessive free radical generation. Recently, curcumin has been implicated as a neuroprotectant in the treatment of various neurological disorders. The present study was designed to investigate the effects of curcumin in 3-NP-induced cognitive impairment and oxidative stress in rats. Curcumin, a potent antioxidant of dietary polyphenol, containing a standardized extract of Curcuma longa root (Zingiberaceae), has been reported to possess free radical scavenging, iron chelating and antiinflammatory activities. Intraperitoneal administration of 3-NP (20 mg/kg for 4 days) showed loss in body weight, declined motor function, poor retention of memory and changes in oxidative stress (lipid peroxidation, reduced glutathione and nitrite level) parameters in brain. Chronic treatment with curcumin (10, 20 and 50 mg/kg, p.o.) once daily for a period of 8 days beginning 4 days prior to 3-NP administration dose-dependently improved the 3-NP-induced motor and cognitive impairment. Biochemical analysis revealed that curcumin administration significantly attenuated 3-NP-induced oxidative stress (lipid peroxidation estimation, reduced glutathione and nitrite activity) in the brains of rats. It also significantly restored the decreased succinate dehydrogenase activity. The results of the present study clearly indicate that curcumin by its antioxidant activity showed neuroprotection against 3-NP-induced behavioral and biochemical alteration. (c) 2007 Prous Science. All rights reserved.

  Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer.:Int J Oncol. 2007 Apr;30(4):905-18.Shankar S, Srivastava RK.Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, TX 75703, USA.

 Curcumin (diferulolylmethane), an active ingredient derived from the rhizome of the plant Curcuma longa, has anticancer activity in vitro and in vivo. Although curcumin possesses chemopreventive properties against several types of cancer, the molecular mechanisms by which it inhibits cell growth and induces apoptosis are not clearly understood. Our data revealed that curcumin inhibited growth and induced apoptosis in androgen-dependent and -independent prostate cancer cells, but had no effect on normal human prostate epithelial cells. Curcumin downregulated the expression of Bcl-2, and Bcl-XL and upregulated the expression of p53, Bax, Bak, PUMA, Noxa, and Bim. Curcumin upregulated the expression of p53 as well as its phosphorylation at serine 15, and acetylation in a concentration-dependent manner. Acetylation of histone H3 and H4 was increased in cells treated with curcumin, suggesting histone modification may regulate gene expression. Treatment of LNCaP cells with curcumin resulted in translocation of Bax and p53 to mitochondria, production of reactive oxygen species, drop in mitochondrial membrane potential, release of mitochondrial proteins (cytochrome c, Smac/DIABLO and Omi/HtrA2), activation of caspase-3 and induction of apoptosis. Furthermore, curcumin inhibited expression of phosphatidyl-inositol-3 kinase (PI3K) p110 and p85 subunits, and phosphorylation of Ser 473 AKT/PKB. Downregulation of AKT by inhibitors of PI3K (Wortmannin and LY294002) and AKT, or by dominant negative AKT increased curcumin-induced apoptosis, whereas transfection of constitutively active AKT attenuated this effect. Similarly, wild-type phosphatase and tensin homolog deleted from chromosome 10 (PTEN) enhanced curcumin-induced apoptosis and, in contrast, inactive PTEN (G129E and G129R) inhibited curcumin-induced apoptosis. Overexpression of constitutively active AKT inhibited curcumin-induced p53 translocation to mitochondria, and Smac release to cytoplasm, whereas inhibition of AKT by dominant negative AKT enhanced curcumin-induced p53 translocation to mitochondria and Smac release. Our study establishes a role for AKT in modulating the direct action of p53 on the caspase-dependent mitochondrial death pathway and suggests that these important biological molecules interact at the level of the mitochondria to influence curcumin sensitivity. These properties of curcumin strongly suggest that it could be used as a cancer chemopreventive agent.

  NMR study of the solution structure of curcumin.:J Nat Prod. 2007 Feb;70(2):143-6.Payton F, Sandusky P, Alworth WL.Department of Chemistry and Coordinated Instrumentation Facility, Tulane University, New Orleans, Louisiana 70118, USA.

 Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is derived from the rhizomes of Curcuma longa. Although early studies concluded that curcumin exists predominantly as a keto-enol tautomer, 1b, in several recent articles the solution structure of curcumin has been represented as a beta-diketone tautomer, 1a. We have investigated the structure of curcumin in solvents ranging in polarity from CDCl3 to mixtures of DMSO-d6 in water, and in buffered aqueous DMSO-d6 solutions with pH values varying from 3 to 9. The solution structure of curcumin was determined on the basis of NMR techniques, including DEPT, HMQC, HMBC, and COSY. The results of the NMR studies show definitely that curcumin exists in solution as keto-enol tautomers, 1b.


  Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage.:Eur J Pharmacol. 2007 Apr 30;561(1-3):54-62. Epub 2007 Jan 19.Jiang J, Wang W, Sun YJ, Hu M, Li F, Zhu DY.Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 210029, China.

 Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Disruption of the blood-brain barrier occurs after stroke. Protection of the blood-brain barrier has become an important target of stroke interventions in experimental therapeutic. The objective of the present study was to determine whether curcumin prevents cerebral ischemia/reperfusion injury by protecting blood-brain barrier integrity. We report that a single injection of curcumin (1 and 2 mg/kg, i.v.) 30 min after focal cerebral ischemia/reperfusion in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality, reduced the water content of the brain and the extravasation of Evans blue dye in ipsilateral hemisphere in a dose-dependent manner. In cultured astrocytes, curcumin significantly inhibited inducible nitric oxide synthase (iNOS) expression and NO(x) (Nitrites/nitrates contents) production induced by lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF(alpha)). Furthermore, curcumin prevented ONOO(-) donor SIN-1-induced cerebral capillaries endothelial cells damage. We concluded that curcumin ameliorates cerebral ischemia/reperfusion injury by preventing ONOO(-) mediated blood-brain barrier damage.

  Bax and Bak genes are essential for maximum apoptotic response by curcumin, a polyphenolic compound and cancer chemopreventive agent derived from turmeric, Curcuma longa.:Carcinogenesis. 2007 Jun;28(6):1277-86. Epub 2007 Feb 2.Shankar S, Srivastava RK.Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, TX 75703, USA.

 Curcumin, an active ingredient of turmeric (Curcuma longa), inhibits proliferation and induces apoptosis in cancer cells, but the sequence of events leading to cell death is poorly defined. The objective of this study was to examine the molecular mechanisms by which multidomain pro-apoptotic Bcl-2 family members Bax and Bak regulate curcumin-induced apoptosis using mouse embryonic fibroblasts (MEFs) deficient in Bax, Bak or both genes. Curcumin treatment resulted an increase in the protein levels of both Bax and Bak, and mitochondrial translocation and activation of Bax in MEFs to trigger drop in mitochondrial membrane potential, cytosolic release of apoptogenic molecules [cytochrome c and second mitochondria-derived activator of caspases (Smac)/direct inhibitor of apoptosis protein-binding protein with low isoelectric point], activation of caspase-9 and caspase-3 and ultimately apoptosis. Furthermore, MEFs derived from Bax and Bak double-knockout (DKO) mice exhibited even greater protection against curcumin-induced release of cytochrome c and Smac, activation of caspase-3 and caspase-9 and induction of apoptosis compared with wild-type MEFs or single-knockout Bax(-/-) or Bak(-/-) MEFs. Interestingly, curcumin treatment also caused an increase in the protein level of apoptosis protease-activating factor-1 in wild-type MEFs. Smac N7 peptide enhanced curcumin-induced apoptosis, whereas Smac siRNA inhibited the effects of curcumin on apoptosis. Mature form of Smac sensitized Bax and Bak DKO MEFs to undergo apoptosis by acting downstream of mitochondria. The present study demonstrates the role of Bax and Bak as a critical regulator of curcumin-induced apoptosis and over-expression of Smac as interventional approaches to deal with Bax- and/or Bak-deficient chemoresistant cancers for curcumin-based therapy.

  Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis.:Int Immunopharmacol. 2007 Mar;7(3):333-42. Epub 2006 Dec 18.Camacho-Barquero L, Villegas I, S¨¢nchez-Calvo JM, Talero E, S¨¢nchez-Fidalgo S, Motilva V, Alarc¨®n de la Lastra C.Department of Pharmacology, School of Pharmacy, University of Seville, Profesor Garc¨ªa Gonz¨¢lez Street, 2, 41012-Seville, Spain.

 Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and up-regulation of pro-inflammatory cytokines. Mitogen-activated protein kinases (MAPKs), such as the p38 and the c-Jun N-terminal kinase (JNK) modulate the transcription of many genes involved in the inflammatory process. Curcumin is a polyphenol derived from Curcuma longa, which is known to have anti-inflammatory activity. The aim of this study was to study the effects and mechanisms of action of curcumin, on chronic colitis in rats. Inflammation response was assessed by histology and myeloperoxidase activity (MPO). We determined the production of Th1 and Th2 cytokines and nitrites in colon mucosa, as well as the expression of inducible nitric oxide synthase (iNOS), cyclo-oxygenase(COX)-1 and-2 by western blotting and inmmunohistochemistry. Finally, we studied the involvement of MAPKs signaling in the protective effect of curcumin in chronic colonic inflammation. Curcumin (50-100 mg/kg/day) were administered by oral gavage 24 h after trinitrobenzensulfonic acid (TNBS) instillation, and daily during 2 weeks before sacrifice. Curcumin significantly attenuated the damage and caused substantial reductions of the rise in MPO activity and tumour necrosis factor alpha (TNF)-alpha. Also curcumine was able to reduce nitrites colonic levels and induced down-regulation of COX-2 and iNOS expression, and a reduction in the activation of p38 MAPK; however, no changes in the activation of JNK could be observed. In conclusion, we suggest that inhibition of p38 MAPK signaling by curcumin could explain the reduced COX-2 and iNOS immunosignals and the nitrite production in colonic mucosa reducing the development of chronic experimental colitis.

  Possible inhibitory mechanism of Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated Caco-2 cells.:Int J Pharm. 2007 Jun 7;337(1-2):169-77. Epub 2007 Jan 7.

 Curcuma longa and C. zedoaria, belonging to genus Curcuma, have become prevalent as supplements in East Asia. Curcumin is the most well-studied bioactive component isolated from rhizomes of C. longa and other Curcuma species except C. zedoaria. In this study, we investigated the affects of C. longa, C. zedoaria from Japan and curcumin on CYP3A4. Caco-2 cells, in which CYP3A4 expression was induced by 1alpha,25-(OH)(2)-D(3), were used to mimic the metabolism of small intestine. Caco-2 cells were treated with methanol extracts from two Curcuma rhizomes (0.1mg/ml) or curcumin (30 microM) for 72 h. Both extracts significantly decreased the activity of CYP3A4 by about 85-98%. The 50% inhibitory concentrations of C. longa and C. zedoaria extracts were 0.019 and 0.014 mg/ml, respectively. They caused a 60-70% decrease in CYP3A4 protein. Otherwise, curcumin treatment caused a 30-40% decrease in CYP3A4 catalytic activity and a 38% decrease in CYP3A4 protein expression. Moreover, it was found that both Curcuma extracts and curcumin treatment had no influence on CYP3A4 mRNA expression. Our results suggested that administration of Curcuma drugs might inhibit the catalytic activity of intestinal CYP3A4. However, curcumin was not the major compound responsible for this inhibitory effect.

  Changes in glycoprotein components in streptozotocin--nicotinamide induced type 2 diabetes: influence of tetrahydrocurcumin from Curcuma longa.:Plant Foods Hum Nutr. 2007 Mar;62(1):25-9. Epub 2007 Jan 17.Pari L, Murugan P.Department of Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar 608002, Tamil Nadu, India. paribalaji@gmail.com

 Curcuma longa (Zingiberaceae) has been used traditionally as antidiabetic, and has been proven scientifically to possess high antioxidant activity and anticancer properties. The active components of Curcuma longa such as curcumin and tetrahydrocurcumin (THC), a major colourless metabolite of curcumin also possesses antidiabetic, antiinflammatory and antioxidant activity. The ethnopharmacological value of this plant, the effect of THC on glycoproteins was carried out in normal and streptozotocin-nicotiniamide induced type 2 hyperglycaemic rats for 45 days. Glucose, plasma insulin and glycoprotein components in plasma and tissues (hexose, hexosamine, fucose and sialic acid) were determined. Oral administration of THC to diabetic rats showed a decrease in the level of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased where as the levels of tissue hexose, hexosamine and fucose were near normal in diabetic rats treated with THC. The present study indicates that the THC possesses a significant beneficial effect on glycoprotein moiety in addition to its antidiabetic effect. The effect of THC is more prominent than curcumin.


  Curcumin and kolaviron ameliorate di-n-butylphthalate-induced testicular damage in rats.:Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):43-8.Farombi EO, Abarikwu SO, Adedara IA, Oyeyemi MO.Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry College of Medicine, University of Ibadan, Ibadan, Nigeria. olatunde_farombi@yahoo.com

 The present study was carried out to evaluate the ameliorative effects of kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days significantly decreased the relative testicular weights compared to the controls, while the weights of other organs remained unaffected. Curcumin or kolaviron did not affect all the organ weights of the animals. While only DBP treatment significantly increased the testicular malondialdehyde level and gamma-glutamyl transferase activity (gamma-GT), it markedly decreased glutathione level, the testicular catalase, glucose-6-phosphate dehydrogenase, superoxide dismutase, sperm gamma-GT activities and serum testosterone level compared to the control group. Data on cauda epididymal sperm count and live/dead ratio were not significantly affected in the DBP-treated rats. Alone, DBP treatment resulted in a 66% decrease in spermatozoa motility and a 77% increase in abnormal spermatozoa in comparison to control. DBP-treated rats showed marked degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. The DBP-induced injuries in biochemical, spermatological parameters and histological structure of testis were recovered by treatment with kolaviron or curcumin. The pattern in the behaviour of these compounds might be correlated with their structural variations. Our results indicate that kolaviron and curcumin protect against testicular oxidative damage induced by DBP. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties and as such may prove useful in combating phthalate-induced reproductive toxicity.

  "Spicing up" of the immune system by curcumin.:J Clin Immunol. 2007 Jan;27(1):19-35. Epub 2007 Jan 9. Review.Jagetia GC, Aggarwal BB.Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

 Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. Traditionally known for its an antiinflammatory effects, curcumin has been shown in the last two decades to be a potent immunomodulatory agent that can modulate the activation of T cells, B cells, macrophages, neutrophils, natural killer cells, and dendritic cells. Curcumin can also downregulate the expression of various proinflammatory cytokines including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, most likely through inactivation of the transcription factor NF-kappaB. Interestingly, however, curcumin at low doses can also enhance antibody responses. This suggests that curcumin's reported beneficial effects in arthritis, allergy, asthma, atherosclerosis, heart disease, Alzheimer's disease, diabetes, and cancer might be due in part to its ability to modulate the immune system. Together, these findings warrant further consideration of curcumin as a therapy for immune disorders.

  Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3.:Anticancer Res. 2006 Nov-Dec;26(6B):4379-89.Su CC, Lin JG, Li TM, Chung JG, Yang JS, Ip SW, Lin WC, Chen GW.School of Chinese Medicine, Department of Microbiology, China Medical University, No 91, Hsueh-Shih Road, Taichung City 404, Taiwan, ROC.

 Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is known to inhibit proliferation of cancer cells by arresting them at various phases of the cell cycle and to induce apoptosis in tumor cells. Curcumin-induced apoptosis mainly involves the activation of caspase-3 and mitochondria-mediated pathway in various cancer cells of different tissue origin. In the present study, the induction of apoptosis and cytotoxicity by curcumin in colon cancer colo 205 cells was investigated by using flow cytometry. The results demonstrated that curcumin induced cytotoxicity and apoptosis dose- and time-depedently. Curcumin induced the production of reactive oxygen species (ROS) and Ca+2, decreased the levels of mitochondria membrane potential and induced caspase-3 activity. Curcumin also promoted the expression of Bax, cytochrome C, p53 and p21 but inhibited the expression of Bcl-2. These observations suggest that curcumin may have a possible therapeutic potential in colon cancer patients.

  Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.:J Immunol. 2007 Jan 1;178(1):111-21. Gururajan M, Dasu T, Shahidain S, Jennings CD, Robertson DA, Rangnekar VM, Bondada S.Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA.

 Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

  Contact urticaria from curcumin.:Dermatitis. 2006 Dec;17(4):196-7.Liddle M, Hull C, Liu C, Powell D.Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.

 Turmeric, a spice derived from the rhizome of the plant Curcuma longa, contains the chemical curcumin, which is responsible for turmeric's taste, color, and biologic properties. Curcumin is used as a spice in foods, as a treatment in traditional medicine, as a dye for fur, and as a component in nutritional supplements. A few cases of allergic contact dermatitis from curcumin have been reported. We report two cases of contact urticaria from curcumin. These cases are mediated by two different mechanisms of contact urticaria: nonimmunologic and immunologic (immunoglobulin-E mediated).


  Metabolic profiling of turmeric (Curcuma longa L.) plants derived from in vitro micropropagation and conventional greenhouse cultivation.:J Agric Food Chem. 2006 Dec 13;54(25):9573-83.Ma X, Gang DR.Department of Plant Sciences and BIO5 Institute, 303 Forbes Building, The University of Arizona, Tucson, AZ 85721-0036, USA.

 Turmeric (Curcuma longa) was considered only a culinary spice in many parts of the world until the notable anti-inflammation curcuminoids were discovered from this herb. Because it is a sterile triploid and is propagated vegetatively by rhizome division, turmeric is susceptible to pathogens that accumulate and are transmitted from generation to generation, and amplification of particularly useful stocks is a slow process. An in vitro propagation method has been developed to alleviate these problems. Metabolic profiling, using GC-MS and LC-ESI-MS, was used to determine if chemical differences existed between greenhouse-grown and in vitro micropropagation derived plants. The major chemical constituent curcuminoids, a group of diarylheptanoid compounds, as well as major mono- and sesquiterpenoids were identified and quantified. Principal component analysis and hierarchical cluster analysis revealed chemical differences between lines (T3C turmeric vs Hawaiian red turmeric) and tissues (rhizome, root, leaf, and shoot). However, this analysis indicated that no significant differences existed between growth treatments (conventional greenhouse-grown vs in vitro propagation derived plants).

  Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test.:J Ethnopharmacol. 2007 Mar 21;110(2):356-63. Epub 2006 Oct 17.Xia X, Cheng G, Pan Y, Xia ZH, Kong LD.State Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecule, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.

 Curcuma longa L. (turmeric) has been used for centuries in traditional Chinese medicine as a treatment for mental disorders including depression. The studies described here were undertaken to determine the behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa using the forced swimming test (FST) in male ICR strain of mice. The ethanolic extract was found to reduce the duration of immobility in the mouse FST when orally administered for 21 days. The extract markedly attenuated swim stress-induced decreases in serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine concentrations, as well as increases in serotonin turnover. Furthermore, the ethanolic extract of Curcuma longa significantly reversed the swim stress-induced increases in serum corticotropin-releasing factor and cortisol levels. Under these conditions, the ethanolic extract of Curcuma longa was partly different from fluoxetine and amitriptyline. These results suggested that antidepressant properties of the ethanolic extract of Curcuma longa was mediated through regulations of neurochemical and neuroendocrine systems and it may be a useful agent against depression.

  Effects of ingested turmeric oleoresin on glucose and lipid metabolisms in obese diabetic mice: a DNA microarray study.:J Agric Food Chem. 2006 Nov 29;54(24):9055-62.

 Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human health. Turmeric oleoresin, an extract of turmeric, is often used for flavoring and coloring. Curcuminoids and turmeric essential oil are both contained in turmeric oleoresin, and both of these fractions have hypoglycemic effects. In the present study, we comprehensively assessed the effect of turmeric oleoresin on hepatic gene expression in obese diabetic KK-Ay mice using DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR). Female KK-Ay mice aged 6 weeks (n = 6/group) were fed a high-fat diet containing turmeric oleoresin, curcuminoids, and essential oil for 5 weeks. The same diet without any of these fractions was used as a control diet. Ingestion of turmeric oleoresin and essential oil inhibited the development of increased blood glucose and abdominal fat mass, while curcuminoids only inhibited the increase in blood glucose. DNA microarray analysis indicated that turmeric oleoresin ingestion up-regulated the expression of genes related to glycolysis, beta-oxidation, and cholesterol metabolism in the liver of KK-Ay mice, while expression of gluconeogenesis-related genes was down-regulated. Real-time PCR analysis was conducted to assess the contribution of the curcuminoids and essential oil in turmeric oleoresin to the changes in expression of representative genes selected by DNA microarray analysis. This analysis suggested that curcuminoids regulated turmeric oleoresin ingestion-induced expression of glycolysis-related genes and also that curcuminoids and turmeric essential oil acted synergistically to regulate the peroxisomal beta-oxidation-related gene expression induced by turmeric oleoresin ingestion. These changes in gene expression were considered to be the mechanism by which the turmeric oleoresin affected the control of both blood glucose levels and abdominal adipose tissue masses. All of these results suggest that the use of whole turmeric oleoresin is more effective than the use of either curcuminoids or the essential oil alone.

  Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal.:J Nutr. 2006 Dec;136(12):2970-4. Tuntipopipat S, Judprasong K, Zeder C, Wasantwisut E, Winichagoon P, Charoenkiatkul S, Hurrell R, Walczyk T.Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand.

 Chili and turmeric are common spices in indigenous diets in tropical regions. Being rich in phenolic compounds, they would be expected to bind iron (Fe)(3) in the intestine and inhibit Fe absorption in humans. Three experiments were conducted in healthy young women (n = 10/study) to assess the effect of chili and turmeric on Fe absorption from a rice-based meal containing vegetables and iron fortified fish sauce in vivo. Iron absorption was determined by erythrocyte incorporation of stable isotope labels ((57)Fe/(58)Fe) using a randomized crossover design. Addition of freeze-dried chili (4.2 g dry powder, 25 mg polyphenols as gallic acid equivalents) reduced Fe absorption from the meal by 38% (6.0% with chili vs. 9.7% without chili, P = 0.0017). Turmeric (0.5 g dry powder, 50 mg polyphenols as gallic acid equivalents) did not inhibit iron absorption (P = 0.91). A possible effect of chili on gastric acid secretion was indirectly assessed by comparing Fe absorption from acid soluble [(57)Fe]-ferric pyrophosphate relative to water soluble [(58)Fe]-ferrous sulfate from the same meal in the presence and absence of chili. Chili did not enhance gastric acid secretion. Relative Fe bioavailability of ferric pyrophosphate was 5.4% in presence of chili and 6.4% in absence of chili (P = 0.47). Despite the much higher amount of phenolics in the turmeric meal, it did not affect iron absorption. We conclude that both phenol quality and quantity determine the inhibitory effect of phenolic compounds on iron absorption.

  Curcumin/turmeric solubilized in sodium hydroxide inhibits HNE protein modification--an in vitro study.:J Ethnopharmacol. 2007 Mar 21;110(2):368-73. Epub 2006 Oct 13.Kurien BT, Scofield RH.Arthritis and Immunology Program, Oklahoma City, OK 73104, USA. biji-kurien@omrf.ouhsc.edu

 Free radical mediated lipid peroxidation has been implicated in multiple diseases. A major oxidation by-product of this deleterious process is 4-hydroxy-2-nonenal (HNE). HNE is cytotoxic, mutagenic and genotoxic and is involved in disease pathogenesis. Curcumin, a non-steroidal anti-inflammatory agent (occurring as the yellow pigment found in the rhizomes of the perennial herb Curcuma longa known as turmeric), has emerged as the newest "nutraceutical" agent that has been shown to be efficacious against colon cancer and other disorders, including correcting cystic fibrosis defects. Since curcumin has been reported to have anti-oxidant properties we hypothesized that it will inhibit HNE-modification of a protein substrate. Using an ELISA that employed HNE-modification of solid phase antigen following immobilization, we found that the curcumin solubilized in dilute alkali (5mM sodium hydroxide, pH 11) inhibited HNE-protein modification by 65%. Turmeric also inhibited HNE-protein modification similarly (65%) but at a much lower alkali level (130muM sodium hydroxide, pH 7.6). Alkali by itself (5mM sodium hydroxide, pH 11) was found to enhance HNE modification by as much as 267%. Curcumin/turmeric has to inhibit this alkali enhanced HNE-modification prior to inhibiting the normal HNE protein modification induced by HNE. Thus, inhibition of HNE-modification could be a mechanism by which curcumin exerts its antioxidant effects. The pH at which the inhibition of HNE modification of substrate was observed was close to the physiological pH, making this formulation of curcumin potentially useful practically.


  Study on ingredients of essential oils of Curcuma wenyujin extracted by supercritical-CO2 fluid extraction and steam distillation.:Zhongguo Zhong Yao Za Zhi. 2006 Sep;31(17):1445-6. Chinese.Li HX, Yang TY, Yang TL, Ge FH, Pan WS, Yang XG, Chen JM.Meilin Hospital, Futian District, Shenzhen 518049, China. lihongxia0755@163.com

 OBJECTIVE: To compare the ingredients of essential oils of Curcuma wenyujin extracted by supercritical-CO2 fluid extraction and by steam distillation. METHOD: GC-MS was applied in this experiment. RESULT: The ingredients and physical and chemical properties of essential oils of C. wenyujin extracted by supercritical-CO2 fluid extraction and by steam distillation are similar. CONCLUSION: Supercritical-CO2 fluid extraction is better than steam distillation in extraction time, power consumption, recovery and purity.

  Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis.:Arthritis Rheum. 2006 Nov;54(11):3452-64.Funk JL, Frye JB, Oyarzo JN, Kuscuoglu N, Wilson J, McCaffrey G, Stafford G, Chen G, Lantz RC, Jolad SD, S¨®lyom AM, Kiela PR, Timmermann BN.University of Arizona, Tucson, USA. jfunk@u.arizona.edu

 OBJECTIVE: Scientific evidence is lacking for the antiarthritic efficacy of turmeric dietary supplements that are being promoted for arthritis treatment. Therefore, we undertook studies to determine the antiarthritic efficacy and mechanism of action of a well-characterized turmeric extract using an animal model of rheumatoid arthritis (RA). METHODS: The composition of commercial turmeric dietary supplements was determined by high-performance liquid chromatography. A curcuminoid-containing turmeric extract similar in composition to these supplements was isolated and administered intraperitoneally to female Lewis rats prior to or after the onset of streptococcal cell wall-induced arthritis. Efficacy in preventing joint swelling and destruction was determined clinically, histologically, and by measurement of bone mineral density. Mechanism of action was elucidated by analysis of turmeric's effect on articular transcription factor activation, microarray analysis of articular gene expression, and verification of the physiologic effects of alterations in gene expression. RESULTS: A turmeric fraction depleted of essential oils profoundly inhibited joint inflammation and periarticular joint destruction in a dose-dependent manner. In vivo treatment prevented local activation of NF-kappaB and the subsequent expression of NF-kappaB-regulated genes mediating joint inflammation and destruction, including chemokines, cyclooxygenase 2, and RANKL. Consistent with these findings, inflammatory cell influx, joint levels of prostaglandin E(2), and periarticular osteoclast formation were inhibited by turmeric extract treatment. CONCLUSION: These translational studies demonstrate in vivo efficacy and identify a mechanism of action for a well-characterized turmeric extract that supports further clinical evaluation of turmeric dietary supplements in the treatment of RA.

  Antimicrobial emulsion (coating) based on biopolymer containing neem (Melia azardichta) and turmeric (Curcuma longa) extract for wound covering.:Biomed Mater Eng. 2006;16(5):329-36.Jagannath JH, Radhika M.Defence Bioengineering and Electrochemical Laboratory, Bangalore, India. mursradhika@yahoo.co.in

 Polymeric bio-adhesives emulsion which is biodegradable and non-toxic containing antimicrobial agents can play an important role in preventing infection in wound covering and coating for surgical implants. Therefore a bioadhesive polymer was synthesized by semi-Interpenetrating Network process using blend of shellac, casein and polyvinyl alcohol and Maleic anhydride (MA) as reactive compatibilizer. The synthesized polymer was mixed with neem and turmeric extract and homogenized using an emulsifier. Differential scanning calorimeter (DSC) was used to measure the molecular miscibility of biopolymer components and emulsion constituents. Stability of emulsion (coating) was measured by keeping property and accelerated stability test. Antimicrobial properties were evaluated for human pathogenic organisms namely E. coli, Staphylococcus aureus, Bacillus cereus, and Salmonella typhimurium using well diffusion assay. The results indicate that stability, miscibility and antimicrobial properties of bioadhesive was satisfactory, however further in vivo studies are required to ascertain suitability of emulsion (coating) for biomedical use.

  Hemagglutinating activity of Curcuma plants.:Fitoterapia. 2007 Jan;78(1):29-31. Epub 2006 Sep 26.Sangvanich P, Kaeothip S, Srisomsap C, Thiptara P, Petsom A, Boonmee A, Svasti J.Research Centre for Bioorganic Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand. spolkit@chula.ac.th

 Crude proteins obtained by Mg/NP-40 extraction from Thai medicinal plants of the Curcuma species exhibited agglutination activity against rabbit erythrocytes. A crude extract from Salingalinthong, a Thai Curcuma specie, exhibited the strongest hemagglutinating activity, 2 x 10(-5) mg/ml.

  Mechanisms of curcumin- and EGF-receptor related protein (ERRP)-dependent growth inhibition of colon cancer cells.:Nutr Cancer. 2006;55(2):185-94.Reddy S, Rishi AK, Xu H, Levi E, Sarkar FH, Majumdar AP.Veterans Affairs Medical Center, Karmanos Cancer Institute, Department of Internal Medicine, Michigan 48201, USA.

 Numerous dietary and pharmacological agents have been proposed as alternative strategies for treatment and prevention of colorectal cancer. Curcumin, an active ingredient of turmeric, that inhibits growth of malignant neoplasms, has a promising role in the prevention and treatment of colorectal cancer. EGF-R related protein (ERRP), a recently identified pan-erbB inhibitor, is a potential therapeutic agent for colorectal cancer. Here we examine whether curcumin together with ERRP will cause a greater inhibition of growth of colon cancer cells than either agent alone and the mechanisms of this inhibition. Human colon cancer HCT-116 or HT-29 cells were incubated with increasing doses of curcumin (up to 10 microM) or ERRP (up to 5 microg/ml), or a combination of both for 48 h. We observed that the cell growth inhibition and stimulation of apoptosis in response to the combinatorial treatment was significantly greater than that caused by either agent alone. These changes were associated with decreased activation (tyrosine phosphorylation) of EGFR, ErbB-2, ErbB-3, and/or IGF-1R. Whereas curcumin inhibited constitutive activation of both EGFR and IGF-1R, ERRP decreased activation of EGFR, ErbB-2, and ErbB-3 but had no effect on IGF-1R. Further, the combination therapy caused a greater attenuation of downstream effectors such as NF-kappaB, Akt and BAD activation, and down-regulation of procaspase-3 than that noted with either agent alone. The superior effects of the combinatorial treatment could partly be attributed to inhibition of constitutive activation of EGFRs and IGF-1R signaling pathways.


  Curcumin content of turmeric and curry powders.:Nutr Cancer. 2006;55(2):126-31.Tayyem RF, Heath DD, Al-Delaimy WK, Rock CL.Clinical Nutrition and Dietetics Department, Allied Health Sciences Faculty, The Hashemite University, Jordan

 Curcumin, derived from the rhizome curcuma longa, is one of the primary ingredients in turmeric and curry powders that are used as spices in Middle Eastern and Asian countries, especially on the Indian subcontinent. More recently, laboratory studies have demonstrated that dietary curcumin exhibits various biological activities and significantly inhibits colon tumorigenesis and tumor size in animals. Curcumin displays both anti-inflammatory and antioxidant properties, giving it the potential to be considered in the development of cancer preventive strategies and applications in clinical research. Experimental studies have shown the biological activities of the compound, but much more information on pharmacokinetics, bioavailability, and food content are needed. Whether the amount of curcumin in turmeric and curry powders is sufficient to suggest effects on biological activities and cancer risk is unknown. To determine and compare the quantitative amounts of curcumin that are present in several brands of turmeric and curry powders, a high performance liquid chromatography technique was used to analyze 28 spice products described as turmeric or curry powders and two negative controls. Pure turmeric powder had the highest curcumin concentration, averaging 3.14% by weight. The curry powder samples, with one exception, had relatively small amounts of curcumin present, and the variability in content was great. The curcumin content of these seasoning products that are consumed as a component of the diet should be considered in evaluating baseline tissue concentration and response to curcumin supplementation, which is under study in chemoprevention trials.

  Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.:Brain Res. 2006 Nov 29;1122(1):56-64. Epub 2006 Oct 3.Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X, Li X.Department of Pharmacology, School of Basic Medical Science, Peking University, 38 Xueyuan Road, Beijing, 100083, PR China.

 Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao-san, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and its antidepressant effects were described in our prior studies in mouse models of behavioral despair. We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Thus in present study we assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior in a chronic unpredictable stress model of depression in rats and examined what its molecular targets may be. We found that subjecting animals to the chronic stress protocol for 20days resulted in performance deficits in the shuttle-box task and several physiological effects, such as an abnormal adrenal gland weight to body weight (AG/B) ratio and increased thickness of the adrenal cortex as well as elevated serum corticosterone levels and reduced glucocorticoid receptor (GR) mRNA expression. These changes were reversed by chronic curcumin administration (5 or 10 mg/kg, p.o.). In addition, we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.

  c-Abl kinase regulates curcumin-induced cell death through activation of c-Jun N-terminal kinase.:Mol Pharmacol. 2007 Jan;71(1):61-72. Epub 2006 Oct 4.Kamath R, Jiang Z, Sun G, Yalowich JC, Baskaran R.Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1205 Biomedical Science Tower, Pittsburgh, PA 15261, USA.

 Curcumin, a natural phenolic compound found in turmeric (Curcuma longa) exhibits anticancer properties, attributed to its antiproliferative and apoptosis-inducing activity. The ubiquitously expressed nonreceptor tyrosine kinase c-Abl regulates stress responses induced by oxidative agents such as ionizing radiation and H2O2. In this study, we show that c-Abl is an important component of the cell death response activated by curcumin and that Abl mediates this response partly through activation of c-Jun N-terminal kinase (JNK). Therefore, inhibition of Abl by STI571 [imatinib (Gleevec)] treatment or down-regulation of Abl expression through Abl-specific short-hairpin RNA (shRNA) diminished cell death induction and JNK activation. Highlighting the interdependent nature of the Abl and JNK signaling in the curcumin-induced cell death response, a JNK inhibitor [anthra(1,9-cd)pyrazol-6(2H)-one-1,9-pyrazoloanthrone (SP600125)] caused very little cell death inhibition in STI571-pretreated cells and in Abl shRNA-expressing cells. Moreover, treatment with Abl and JNK inhibitor alone or together caused similar levels of cell death inhibition. Although p53 induction in response to curcumin treatment is dependent on Abl, we found that Abl-->p53 signaling is not necessary for curcumin-induced cell death. Taken together, the results demonstrate the differential roles played by Abl-->p53 and Abl-->JNK signaling events in modulating the cell death response to curcumin.

  Simultaneous determination of 11 characteristic components in three species of Curcuma rhizomes using pressurized liquid extraction and high-performance liquid chromatography.:J Chromatogr A. 2006 Nov 17;1134(1-2):226-31. Epub 2006 Oct 2.Yang FQ, Wang YT, Li SP.Institute of Chinese Medical Sciences, University of Macau, Macau, China.

 A high-performance liquid chromatography coupled with diode array detection (HPLC-DAD) and pressurized liquid extraction was developed for simultaneous quantitative determination of 11 characteristic compounds, including curcumenone, curcumenol, neocurdione, curdione, isocurcumenol, furanodienone, curcumol, germacrone, curzerene, furanodiene and beta-elemene, in rhizomes of three species of Curcuma. The analysis was performed on an ODS C18 column. The mobile phase consisted of (A) water and (B) acetonitrile using a gradient elution. The peaks were monitored at both 214 nm and 256 nm. All calibration curves showed good linearity (r2 > 0.9996) within test ranges. This method showed good repeatability for the quantification of these eleven components in three species Curcuma rhizomes with intra- and inter-day variations of less than 1.57% and 1.98%, respectively. The validated method was successfully applied to quantify 11 investigated components in eighteen samples of three species of Curcuma, which is helpful to control their quality.

  Study on effects of extracts from Salvia Miltiorrhiza and Curcuma Longa in inhibiting phosphorylated extracellular signal regulated kinase expression in rat's hepatic stellate cells.:Chin J Integr Med. 2006 Sep;12(3):207-11.Cheng Y, Ping J, Liu C, Tan YZ, Chen GF.Department of Hepatocirrhosis, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. chengyang@smmail.com

 OBJECTIVE: To study the effect of salvianolic acid B (SAB) and curcumin, the extracts of Salvia Miltiorrhiza and Curcuma Longa, on the proliferation and activation of hepatic stellate cell (HSC), and the extracellular signal regulated kinase (ERK) expression in it. METHODS: Rat's HSC-T6 were cultured and treated by SAB or curcumin. The inhibitory effect on cell proliferation was determined by 3-(4, 5-dimthyl-2-2thiazoly)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) colorimetry, and the expression levels of alpha smooth actin (alpha-SMA), collagen type I, and ERK were determined by Western blot. RESULTS: SAB and curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose-dependent fashion and significantly reduced the expression level of alpha-SMA (P < 0.01). Curcumin significantly reduced the expression of collagen type I (P < 0.05). Both SAB and curcumin showed insignificant effect on the ERK expression level, but they could significantly reduce the level of phosphorylated-ERK expression, showing significant difference as compared with that in the control group (P < 0.01 and P < 0.05 respectively). CONCLUSION: SAB and curcumin could significantly inhibit the proliferation, activation of HSC, and the production of type I collagen in HSC, the mechanism may be associated with their inhibition on ERK phosphorylation.


  Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats.:Clin Exp Pharmacol Physiol. 2006 Oct;33(10):940-5.Sharma S, Kulkarni SK, Chopra K.Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

 Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.

  Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic pathways for apoptosis in human glioblastoma T98G cells.:Neurosci Lett. 2006 Oct 16;407(1):53-8. Epub 2006 Sep 1.Karmakar S, Banik NL, Patel SJ, Ray SK.Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 323K, P.O. Box 250606, Charleston, SC 29425, USA.

 The therapeutic effect of curcumin (CCM), a polyphenolic compound from the rhizome of Curcuma longa, has not yet been examined in glioblastoma. We used human glioblastoma T98G cells to explore the efficacy of CCM for inducing apoptosis and identifying proteolytic mechanisms involved in this process. Trypan blue dye exclusion test showed decrease in cell viability with increasing dose of CCM. Wright staining and ApopTag assay showed, respectively, morphological and biochemical features of apoptosis in T98G cells exposed to 25 microM and 50 microM of CCM for 24 h. Treatment with CCM activated receptor-mediated pathway of apoptosis as Western blotting showed activation of caspase-8 and cleavage of Bid to tBid. Besides, CCM caused an increase in Bax:Bcl-2 ratio, and mitochondrial release of cytochrome c, Second mitochondrial activator of caspases/Direct IAP binding protein with low pI (Smac/Diablo), and apoptosis-inducing-factor (AIF) indicating involvement of mitochondria-mediated pathway as well. Down regulation of the nuclear factor kappa B (NFkappaB), increased expression of inhibitor of nuclear factor kappa B alpha (IkappaB alpha), and decreased expression of inhibitor-of-apoptosis proteins (IAPs) such as c-IAP1 and c-IAP2 in T98G cells following CCM treatment suggested suppression of survival signal. Activation of caspase-9 and caspase-3 was detected in generation of 35 kD and 20 kD active fragments, respectively. Calpain and caspase-3 activities cleaved 270 kD alpha-spectrin at specific sites to generate 145 kD spectrin break down product (SBDP) and 120 kD SBDP, respectively. Our results strongly suggest that CCM induced both receptor-mediated and mitochondria-mediated proteolytic mechanisms for induction of apoptosis in T98G cells.

  Quantitative determination of eight components in rhizome (Jianghuang) and tuberous root (Yujin) of Curcuma longa using pressurized liquid extraction and gas chromatography-mass spectrometry.:J Pharm Biomed Anal. 2007 Jan 17;43(2):486-92. Epub 2006 Aug 23.Qin NY, Yang FQ, Wang YT, Li SP.Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.

 Curcuma longa (Zingiberaceae) is a native plant of southern Asia and is cultivated extensively throughout the warmer parts of the world. Jianghuang and Yujin are rhizome and tuberous root of C. longa, respectively, which were traditionally used as two Chinese medicines. In this paper, pressurized liquid extraction (PLE) and gas chromatography-mass spectrometry (GC-MS) were developed for quantitative determination/estimation of eight characteristic compounds including beta-caryophyllene, ar-curcumene, zingiberene, beta-bisabolene, beta-sesquiphellandrenendrene, ar-turmerone, alpha-turmerone and beta-turmerone in Jianghuang and Yujin. A HP-5MS capillary column (30 m x 0.25 mm i.d.) coated with 0.25 microm film 5% phenyl methyl siloxane was used for separation and selected ion monitoring (SIM) method was used for quantitation. Hierarchical cluster analysis based on characteristics of eight identified peaks in GC-MS profiles showed that 10 samples were divided into two main clusters, Jianghuang and Yujin, respectively. Four components such as ar-curcumene, ar-turmerone, alpha-turmerone and beta-turmerone were optimized as markers for quality control of rhizome (Jianghuang) and tuberous root (Yujin), which are two traditional Chinese medicines, from Curcuma longa.

  Experimental study on rat model of endometriosis treated with tamoxifen and rhizoma curcumae oil.:Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Jul;37(4):596-8. Chinese.Kong Y, Zhang JW.Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu 610041, China.

 OBJECTIVE: To evaluate the therapeutic effect of Tamoxifen in conjunction with a cell apoptosis contributor--Rhizoma curcumae oil on the rat endometriosis models. METHODS: The rat endometriosis models were established and were randomly assigned into the control group, Tamoxifen group, Alarelin (GnRHa) group, and the group of Tamoxifen (by gastrogavage) plus Rhizoma curcumae oil (by intraperitoneal injection). After 4 weeks of treatment, the growth of ectopic endometrial implants was observed; then eutopic and ectopic endometria were excised in preparation for HE staining and streptavedin-peroxi-dase immunohisto chemical analysis. RESULTS: After treatment, the volume of the ectopic implants of each treatment group was markedly smaller than that of control and before treatment (P < 0.05); the score of VEGF showed significant difference when each treatment group was compared with control (P < 0.05). The score of VEGF exhibited marked difference between Tamoxifen group and Alarelin (GnRHa) group, between Tamoxifen group and Tamoxifen plus Rhizoma curcumae oil group (P < 0.05). CONCLUSION: Tamoxifen in conjunction with Rhizoma curcumae oil could decrease markedly the volume and VEGF expression of ectopic implants.

  Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger (Zingiber officinale): identification of curcuminoid synthase and hydroxycinnamoyl-CoA thioesterases.:Phytochemistry. 2006 Sep;67(18):2017-29. Epub 2006 Aug 7.Ramirez-Ahumada Mdel C, Timmermann BN, Gang DR.Arizona Center for Phytomedicine Research and Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721-0036, USA.

 Members of the Zingiberaceae such as turmeric (Curcuma longa L.) and ginger (Zingiber officinale Rosc.) accumulate at high levels in their rhizomes important pharmacologically active metabolites that appear to be derived from the phenylpropanoid pathway. In ginger, these compounds are the gingerols; in turmeric these are the curcuminoids. Despite their importance, little is known about the biosynthesis of these compounds. This investigation describes the identification of enzymes in the biosynthetic pathway leading to the production of these bioactive natural products. Assays for enzymes in the phenylpropanoid pathway identified the corresponding enzyme activities in protein crude extracts from leaf, shoot and rhizome tissues from ginger and turmeric. These enzymes included phenylalanine ammonia lyase, polyketide synthases, p-coumaroyl shikimate transferase, p-coumaroyl quinate transferase, caffeic acid O-methyltransferase, and caffeoyl-CoA O-methyltransferase, which were evaluated because of their potential roles in controlling production of certain classes of gingerols and curcuminoids. All crude extracts possessed activity for all of these enzymes, with the exception of polyketide synthases. The results of polyketide synthase assays showed detectable curcuminoid synthase activity in the extracts from turmeric with the highest activity found in extracts from leaves. However, no gingerol synthase activity could be identified. This result was explained by the identification of thioesterase activities that cleaved phenylpropanoid pathway CoA esters, and which were found to be present at high levels in all tissues, especially in ginger tissues. These activities may shunt phenylpropanoid pathway intermediates away from the production of curcuminoids and gingerols, thereby potentially playing a regulatory role in the biosynthesis of these compounds.


  Optimization of GC-MS conditions based on resolution and stability of analytes for simultaneous determination of nine sesquiterpenoids in three species of Curcuma rhizomes.:J Pharm Biomed Anal. 2007 Jan 4;43(1):73-82. Epub 2006 Jul 24.Yang FQ, Li SP, Zhao J, Lao SC, Wang YT.Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau.

 GC-MS is a powerful tool for analysis of volatile oil, and resolutions of analytes were exclusively used as marker for optimization of the conditions. However, volatile oil usually contains heat labile components which may degrade and result in wrong results during GC analysis. In present study, based on both resolutions and stabilities of 11 sesquiterpenoids, GC-MS conditions were optimized for simultaneously quantitative determination of nine compounds including beta-elemene, curzerene, curcumol, isocurcumenol, germacrone, curdione, curcumenol, neocurdione and curcumenone in Ezhu. However, the other two compounds, i.e. furanodienone and furanodiene, were still thermal sensitive and not available for GC analysis. The results showed that both resolutions and stabilities of analytes should be considered for optimization of GC conditions because the properties of most components in volatile oil are unknown. Under optimum conditions, a capillary column (30 m x 0.25 mm i.d.) coated with 0.25 microm film 5% phenyl methyl siloxane was used for separation. Pulsed splitless inlet with temperature of 190 degrees C was selected for sample injection (0.2 microl). The calibration curves of nine sesquiterpenoids showed good linearity (r2>0.9989) within test ranges. The optimized method showed good repeatability for quantification of these nine components in Ezhu with intra- and inter-day variations of less than 1.42% and 2.79%, respectively. The validated method was successfully applied to quantify 9 sesquiterpenoids in 18 samples of 3 species of Curcuma used as Ezhu.

  Curcumin inhibits telomerase activity in human cancer cell lines.:Int J Mol Med. 2006 Aug;18(2):227-31.Cui SX, Qu XJ, Xie YY, Zhou L, Nakata M, Makuuchi M, Tang W.Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China.

 Curcumin, one of the major components of tumeric, the dried rhizome of Curcuma longa L, has been shown to have anti-proliferating and anti-carcinogenic properties. In this study, we examined the effects of curcumin on cell growth and telomerase activity in human cancer cell lines Bel7402, HL60 and SGC7901. Curcumin (1-32 microM) showed anti-proliferating effects on these cell lines in a dose-dependent manner in vitro, and anti-tumor effects when curcumin (50-200 mg/kg) was orally administered to nude mice transplanted with the cancer cells. When the cells were treated with 1 microM of curcumin for 120 h, apoptotic cells were observed by means of the adridine orange/ethidium bromide staining method, single cell microgel electrophoresis and flow cytometric analysis. On the other hand, suppression of telomerase activity in extracts of the cells treated with 1 microM of curcumin was observed by means of a telomeric repeat amplification protocol - silver staining assay. These results suggest that curcumin could suppress telomerase activity in the cancer cell lines and that the decrease of telomerase expression followed by induction of apoptosis might be involved in the anti-proliferating effect of curcumin.

  Turmeric and curcumin modulate the conjugation of 1-naphthol in Caco-2 cells.:Biol Pharm Bull. 2006 Jul;29(7):1476-9

 Turmeric, the powdered dry rhizome of the Curcuma longa plant, and curcumin, the major anti-oxidant constituent of turmeric, have been shown to possess chemopreventive activity. To elucidate the possible interaction of turmeric and curcumin with conjugation reactions, which in many cases are involved in the activation of procarcinogens, we measured their effects in the conjugation of 1-naphthol in Caco-2 cells, a human colon carcinoma cell line, within a 24 h period. Turmeric exhibits inhibitory activity toward both sulfo- and glucuronosyl conjugations of 1-naphthol at approximately the same levels (IC(50)=0.24 and 0.29 mg/ml, respectively). Curcumin inhibits sulfo-conjugation at lower concentrations (IC(50)=9.7 microg/ml), but only showed weak inhibition toward glucuronosyl conjugation of 1-naphthol in Caco-2 cells. In addition, turmeric was found to strongly inhibit in vitro phenol sulfotransferase (SULT) activity and demonstrate moderate inhibitory properties against UDP-glucuronosyl transferase (UGT) activity in Caco-2 cells (IC(50)=0.17 mg/ml and 0.62 mg/ml, respectively). Curcumin also strongly inhibits in vitro phenol sulfotransferase activity with an IC(50) of 2.4 microg/ml. Moreover, and in contrast to the moderate inhibition of UGT activity by turmeric and curcumin, both induce the expression of the UGT1A1 and UGT1A6 genes, revealed by real-time PCR analysis. These findings are indicative of a possible interaction of both turmeric and curcumin with conjugation reactions in the human intestinal tract and colon. This in turn may affect the bioavailability of therapeutic drugs and toxicity levels of environmental chemicals, particularly procarcinogens.

  Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators.:Altern Med Rev. 2006 Jun;11(2):128-50. Review.Spelman K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M.Clinical Division, Department of Herbal Medicine, Tai Sophia Institute, 7750 Montpelier Road, Laurel, MD 20723, USA. spelman123@earthlink.net.

 Modulation of cytokine secretion may offer novel approaches in the treatment of a variety of diseases. One strategy in the modulation of cytokine expression may be through the use of herbal medicines. A class of herbal medicines, known as immunomodulators, alters the activity of immune function through the dynamic regulation of informational molecules such as cytokines. This may offer an explanation of the effects of herbs on the immune system and other tissues. For this informal review, the authors surveyed the primary literature on medicinal plants and their effects on cytokine expression, taking special care to analyze research that utilized the multi-component extracts equivalent to or similar to what are used in traditional medicine, clinical phytotherapy, or in the marketplace. METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify research on botanical medicines, in whole or standardized form, that act on cytokine activity through different models, i.e., in vivo (human and animal), ex vivo, or in vitro. RESULTS: Many medicinal plant extracts had effects on at least one cytokine. The most frequently studied cytokines were IL-1, IL-6, TNF, and IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea purpurea, Grifola frondosa, Harpagophytum procumbens, Panax ginseng, Polygala tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia, Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple cytokines. CONCLUSION: The in vitro and in vivo research demonstrates that the reviewed botanical medicines modulate the secretion of multiple cytokines. The reported therapeutic success of these plants by traditional cultures and modern clinicians may be partially due to their effects on cytokines. Phytotherapy offers a potential therapeutic modality for the treatment of many differing conditions involving cytokines. Given the activity demonstrated by many of the reviewed herbal medicines and the increasing awareness of the broad-spectrum effects of cytokines on autoimmune conditions and chronic degenerative processes, further study of phytotherapy for cytokine-related diseases and syndromes is warranted.

  Curcumin's biphasic hormetic response on proteasome activity and heat-shock protein synthesis in human keratinocytes.:Ann N Y Acad Sci. 2006 May;1067:394-9.Ali RE, Rattan SI.Laboratory of Cellular Ageing, Danish Centre for Molecular Gerontology, Department of Molecular Biology, University of Aarhus, Denmark.

 Curcumin (diferuloylmethane), is a component of the yellow powder prepared from the roots of Curcuma longa (Zingiberaceae), also known as tumeric or turmeric. It is widely cultivated and used as a food ingredient in tropical areas of Asia and Central America. Treatment of mid-passage human epidermal keratinocytes with curcumin resulted in a biphasic hormetic dose-response with respect to proteasome activity. Curcumin treatment (up to 1 microM for 24 h) increased chymotrypsin-like activity by 46% compared to that in untreated keratinocytes. However, higher concentrations of curcumin were inhibitory, and at 10 microM the proteasome activity decreased to 46% of its initial value. Furthermore, the preincubation of human keratinocytes at 43 degrees C for 1 h, followed by 24-h treatment with 3 microM curcumin, led to an increase in heat-shock protein (hsp70 and hsp90) levels by 24% and 19%, respectively, and the effect was sustained at concentrations up to 10 microM. On the other hand, the level of the small hsp27 was unaffected by curcumin concentrations of 0.3-1 microM, while it decreased by 34% at 10 microM.


  Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes: A Possible Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract.:Evid Based Complement Alternat Med. 2006 Jun;3(2):255-60. Epub 2006 Apr 5.Tohda C, Nakayama N, Hatanaka F, Komatsu K.

 We aimed to compare the anti-inflammatory activities of six species of Curcuma drugs using adjuvant arthritis model mice. When orally administered 1 day before the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling and the serum haptoglobin concentration in adjuvant arthritis mice. Also when orally administered 1 day after the injection of adjuvant, the methanol extract of Curcuma phaeocaulis significantly inhibited paw swelling. Other Curcuma species (Curcuma longa, Curcuma wenyujin, Curcuma kwangsiensis, Curcuma zedoaria and Curcuma aromatica) had no significant inhibitory effects on adjuvant-induced paw swelling. Cyclooxygenase (COX)-2 activity was significantly inhibited by the methanol extract of C. phaeocaulis. Curcuminoids' (curcumin, bis-demethoxycurcumin and demethoxycurcumin) were rich in C. longa, but less in C. phaeocaulis and C. aromatica, not in C. wenyujin, C. kwangsiensis and C. zedoaria, suggesting that curcuminoids' contents do not relate to inhibition of arthritis swelling. Therefore, C. phaeocaulis may be a useful drug among Curcuma species for acute inflammation, and the active constituents of C. phaeocaulis are not curcuminoids.

  Experimental study on protective effects of curcumin on exaggerated extracellular matrix accumulation of pulmonary fibrosis rats:Zhongguo Zhong Yao Za Zhi. 2006 Apr;31(7):570-3. Chinese.Zhou G, Wang JF, Niu JZ, Lu YS, Chen WT, Li ZH, Lin TX.Laboratory of Cell and Biochemistry, Beijing University of Traditional Chinese Medicine, Beijing 100029, China.

 OBJECTIVE: To study the protective effects of curcumin on exaggerated extracellular matrix accumulation of pulmonary fibrosis rats. METHOD: One hundred and forty-four male Sprague-Dawley rats were randomly divided into 6 groups (24 rats in each group). Rats in the model control group, positive medicine group, and high, moderate and low curcumin groups were injected with a single dose of bleomycin by trachea, and rats in sham-model control group with same volume normal saline. One day after the injection, curcumin solution of different dosages (200, 100, 50 mg x kg(-1) x d(-1)) was respectively given to rats in the high, moderate and low curcumin group daily by gastrogavage, while equal volume of normal saline was given to those in the sham-model control group and model control group, and an equal volume of prednisone (0.56 mg x kg(-1) x d(-1)) was given to those in positive medicine control group. On the 7, 14, 28 days, 8 rats per treatment group were randomly killed, the levels of III-collagen, IV-collagen, laminin and hyaluronic acid in the serum were determined, the determination of hydroxyproline in lung homogenates was analyzed, and the lung was incised to make pathological sections which were stained with HE and Mallory. RESULT: Curcumin could decreas the levels of III-collagen, IV-collagen, laminin and hyaluronic acid in the serum, and inhihit the proliferation of fibrous tissue. CONCLUSION: Curcumin may play its therapetuic role by leveling down the content of extracellular matrix in rats with pulmonary fibrosis induced by bleomycin.

  Down-regulation of prostaglandin E2 by curcumin is correlated with inhibition of cell growth and induction of apoptosis in human colon carcinoma cell lines.:J Soc Integr Oncol. 2006 Winter;4(1):21-6.Lev-Ari S, Maimon Y, Strier L, Kazanov D, Arber N.Unit of Complementary Medicine and Department of Cancer Prevention, Tel Aviv Medical Center, Tel Aviv, Israel.

 Several in vitro and in vivo studies have demonstrated an association between curcumin, a diferuloylmethane derived from the plant Curcuma longa, and colorectal cancer (CRC) prevention. Nevertheless, the molecular mechanism responsible for the chemopreventive effect of curcumin is not well understood and most probably involves several pathways. Several studies indicate that curcumin may exert its effect by specifically inhibiting the cyclooxygenase-2 (COX-2) isoenzyme, which is up-regulated in 40 to 50% of colorectal polyps and in up to 85% of CRCs. However, other studies have suggested that curcumin may also inhibit polyps formation by COX-2 independent mechanisms (eg, inhibition of ErbB-1, AkT). The aim of this study was to evaluate whether curcumin's effect on the inhibition of cell growth and induction of apoptosis in human colon carcinoma cell lines is correlated with inhibition of PGE2 synthesis and down-regulation of COX-2. HT29 cells (expressing COX-2) and SW480 (deficient of COX-2) were exposed to different concentrations (0-50 microM) of curcumin for 72 hours. Growth inhibition was assessed by Coulter counter. Cell viability was assessed by the ability of metabolically active cells to reduce tetrazolium salt to colored formazan compounds (tetrazolium salt assay). Apoptosis was measured by two independent methods: flow cyto-metric analysis and 4'-6-Diamidino-2-phenylindole (DAPI) staining. Activity of COX-2 was evaluated by measuring prostaglandin E2 (PGE2) concentration using a specific enzyme-linked immunoassay. COX-1 and COX-2 expressions were measured by Western blot analysis. There was a significant difference between curcumin effect on COX-2-expressing (HT29: inhibitory concentration 50% [IC50] = 15 microM) and COX-2-deficient (SW480: IC50 = 40 microM) cells. Similarly, induction of apoptosis was higher in cells expressing COX-2. Western blot analysis and PGE2 immunoassay showed that curcumin inhibited COX-2 protein activity and expression in a dose-dependent manner. In conclusion, inhibition of cell survival and induction of apoptosis by curcumin in colorectal adenocarcinoma cell lines is associated with the inhibition of PGE2 synthesis and down-regulation of COX-2.

  Resistance to apoptosis of HCW-2 cells can be overcome by curcumin- or vincristine-induced mitotic catastrophe.:Int J Cancer. 2006 Oct 15;119(8):1811-8. Magalska A, Sliwinska M, Szczepanowska J, Salvioli S, Franceschi C, Sikora E.Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland

 The term mitotic catastrophe has recently become widely used to describe a form of death affecting many cancer cells, which, because of severe DNA or mitotic spindle damage, are not able to bypass mitosis. We show here that cells of the HL-60-derived HCW-2 line highly resistant to apoptosis, upon treatment with curcumin or vincristine, undergo mitotic catastrophe that is finalized by caspase 3 activation and oligonucleosomal DNA degradation. Curcumin is a natural dye, derived from Curcuma longa that has been shown to induce cell death in many cancer cells. Both treatments decrease cell proliferation and cell survival, arrest cells in G2/M phase of cell cycle and induce morphological changes characterized by cell enlargement and micronucleation. "Catastrophic" cells comprise a separate subpopulation with less than 4C DNA, as evidenced by flow and scanning cytometry. This subpopulation is MPM-2 positive. Thymidine block increased the number of cell arrested in the G2/M phase of cell cycle and curcumin effectiveness as an inducer of mitotic catastrophe. Curcumin, but not vincristine, acts on HCW-2 cells by inhibiting the expression of survivin, a modulator of cell division and apoptosis in cancer. Altogether our results show that apoptosis resistance can be overcome by inducing mitotic catastrophe in HCW-2 cells.

  Biological effects of curcumin and its role in cancer chemoprevention and therapy.:Anticancer Agents Med Chem. 2006 May;6(3):259-70. Review.Singh S, Khar A.Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.

 Curcumin, a natural component of the rhizome of curcuma longa has emerged as one of the most powerful chemopreventive and anticancer agents. Its biological effects range from antioxidant, anti-inflammatory to inhibition of angiogenesis and is also shown to possess specific antitumoral activity. The molecular mechanism of its varied cellular effects has been studied in some details and it has been shown to have multiple targets and interacting macromolecules within the cell. Curcumin has been shown to possess anti-angiogenic properties and the angioinhibitory effects of curcumin manifest due to down regulation of proangiogenic genes such as VEGF and angiopoitin and a decrease in migration and invasion of endothelial cells. One of the important factors implicated in chemoresistance and induced chemosensitivity is NFkB and curcumin has been shown to down regulate NFkB and inhibit IKB kinase thereby suppressing proliferation and inducing apoptosis. Cell lines that are resistant to certain apoptotic inducers and radiation become susceptible to apoptosis when treated in conjunction with curcumin. Besides this it can also act as a chemopreventive agent in cancers of colon, stomach and skin by suppressing colonic aberrant crypt foci formation and DNA adduct formation. This review focuses on the various aspects of curcumin as a potential drug for cancer treatment and its implications in a variety of biological and cellular processes vis-¨¤-vis its mechanism of action.


  Effects of Yifuning capsule on blood lipids of ovariectomized hyperlipidemia rats.:Zhongguo Zhong Yao Za Zhi. 2006 Mar;31(5):414-6. Chinese.Wang ZX, Deng HZ, Chen JG, Liu PZ.College of Traditional Chinese Medicine and Pharmacy, Southern Medical University, Guangzhou, China.

 OBJECTIVE: To observe the effects of Yifuning (YEN) capsule on blood lipids of ovariectomized hyperlipidemia rats. METHOD: Fifty-six female mature Sprague-Dawley rats were randomized into 7 groups: normal control group, model control group, diethylstilbestrol tablets (DT) group, Xuezhikang group, YFN high, middle and low dose groups. The ovariectomized rats were fed on high fat diet and administrated with the drugs for 3 weeks, then were killed and estimated body weight, liver index and five items of blood lipid (TC, TG, HDL-C, LDL-C, VLDL) by test kit. Enzyme (such as HP, LDL, and whole lipase) was detected too. RESULT: The weight and liver index of model control group increased obviously as compared with normal group. YFN could reduce TG, TC, and LDL-C (P < 0.05) of ovariectomized hyperlipidemia rats obviously and increase HP, LDL and whole lipase (P < 0.05) on the other hand. CONCLUSION: YFN can ameliorate blood lipids of ovariectomized hyperlipidemia rats.

  Determination of curcumol in Rhizoma Curcumae by GC.:Zhongguo Zhong Yao Za Zhi. 2006 Mar;31(5):389-90. Chinese.Zhu YE, Zhu XP.Center Analysis & Measurement of Zhejiang University, Hangzhou, China. zhuyaer@zju.edu.cn

 OBJECTIVE: To establish a method to determine the content of Curcumol in Rhizoma Curcumae. METHOD: The samples were determined by GC on a HP-5 column (0.32 mm x 30 m, 0.25 micron), Inlet temperature 200 degrees C, FID 250 degrees C, flow 1.0 mL x min(-1), splitless. Temperature programming started at 60 degrees C, holding for 4 min, then increased to 210 degrees C at a rate of 3 degrees C x min(-1). RESULT: The calibration curve of curcumol is linear over the range of 40.0-2,000 microg x mL(-1), r = 0.9997. The high and low additive recovery were 95.01% (RSD 2.52%), 96.46% (RSD 2.86%). CONCLUSION: This method was accurate and reliable with a good reproducibility, and the procedure of samples pretreatment is simple.

  Curcumin combats against cigarette smoke and ethanol-induced lipid alterations in rat lung and liver.:Mol Cell Biochem. 2006 Aug;288(1-2):115-23. Epub 2006 May 12.Vanisree AJ, Sudha N.Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600033, Tamilnadu, India. vanielango@yahoo.com

 BACKGROUND: Human population, in spite of the medical and scientific achievements, still fall as a prey to the evils of habitual smoking and alcohol, thus necessitating safer counteracting measures. Objective: To evaluate the effect of cotreatment of curcumin (Curcuma longa) in rats subjected to acute exposure to cigarette smoke (CS) and ethanol (EtOH). METHODOLOGY: Of the four groups of experimental rats, a set of rats was subjected to whole body exposure to cigarette smoke along with ethanol administration serving as a model of CS+EtOH injury. Curcumin treatment was given to two sets of rats: (i) one set receiving simultaneous CS+EtOH and (ii) one set of normal rats without any administration. The other group of rats served as control. Blood, liver and lung of rats were selected for assessment of CS+EtOH injury as well as curcumin treatment. RESULT: Altered lipid, lipoprotein profile and bile acid excretion were observed in CS+EtOH rats along with premalignant pathological state in tissues. In treated rats, the levels were maintained at near-normal levels along with near-normal histology. CONCLUSION: This biochemical picture on cotreatment with curcumin suggests that curcumin could counteract the injurious effects of combined CS and EtOH and thus might help to reduce the risk of hyperlipidemic disorders which develop due to smoking and drinking.

  Inhibition of homodimerization of Toll-like receptor 4 by curcumin.:Biochem Pharmacol. 2006 Jun 28;72(1):62-9. Epub 2006 Apr 1.Youn HS, Saitoh SI, Miyake K, Hwang DH.USDA, ARS, Western Human Nutrition Research Center, and Department of Nutrition, University of California, Davis, Meyer Hall, One Shields Ave., CA 95616, USA.

 Toll-like receptors play a key role in sensing microbial components and inducing innate immune responses. Ligand-induced dimerization of TLR4 is required for the activation of downstream signaling pathways. Thus, the receptor dimerization may be one of the first lines of regulation in activating TLR-mediated signaling pathways and induction of subsequent immune responses. LPS induces the activation of NF-kappaB and IRF3 through MyD88- or TRIF-dependent pathways. Curcumin, a polyphenol found in the plant Curcuma longa, has been shown to suppress the activation of NF-kappaB induced by various pro-inflammatory stimuli by inhibiting IKKbeta kinase activity in MyD88-dependent pathway. Curcumin also inhibited LPS-induced IRF3 activation. These results imply that curcumin inhibits both MyD88- and TRIF-dependent pathways in LPS-induced TLR4 signaling. However, in TRIF-dependent pathway, curcumin did not inhibit IRF3 activation induced by overexpression of TRIF in 293T cells. These results suggest that TLR4 receptor complex is the molecular target of curcumin in addition to IKKbeta. Here, we report biochemical evidence that phytochemicals (curcumin and sesquiterpene lactone) inhibit both ligand-induced and ligand-independent dimerization of TLR4. Furthermore, these results demonstrate that small molecules with non-microbial origin can directly inhibit TLRs-mediated signaling pathways at the receptor level. These results imply that the activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain dietary phytochemicals we consume daily.

  Fast determination of curcumol, curdione and germacrone in three species of Curcuma rhizomes by microwave-assisted extraction followed by headspace solid-phase microextraction and gas chromatography-mass spectrometry.:J Chromatogr A. 2006 Jun 9;1117(2):115-20. Epub 2006 May 5.Deng C, Ji J, Li N, Yu Y, Duan G, Zhang X.Department of Chemistry, Fudan University, Shanghai 200433, China.

 Curcumol, germacrone and curdione are the main active ingredients in a common traditional Chinese medicine (TCM) of Rhizoma Curcuma, and commonly used as the TCM quality control markers. In the present work, microwave-assisted extraction (MAE) followed by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) was developed for the quantitative analysis of curcumol, curdione and germacrone in Rhizoma Curcuma. The MAE and HS-SPME parameters were studied, and the method was validated. The optimal MAE conditions obtained were: microwave power of 700 W and irradiation time of 4 min, and HS-SPME optimal conditions were: fiber coating of 100 microm PDMS, extraction temperature of 80 degrees C, extraction time of 20 min, stirring rate of 1,100 rpm, and salt concentration of 30% NaCl. The proposed method provided good precision (RSD less than 12%) and recoveries between 86% and 93%. The proposed method was applied to the determination of the three marker compounds in three species of Curcuma rhizomes (Curcuma wenyujin, Curcuma phaeocaulis, and Curcuma kwangsiensis). To demonstrate the proposed method reliability, a conventional technique of steam distillation was also used for the analysis of curcumol, germacrone and curdione in the TCMs. The results show that MAE-HS-SPME is a simple, rapid, solvent-free and reliable method for the determination of curdione, curcumol and germacrone in TCM, and also a potential and powerful tool for quality assessment of Rhizoma Curcuma.


  Ethanolic extracts from Curcuma longa attenuates behavioral, immune, and neuroendocrine alterations in a rat chronic mild stress model.:Biol Pharm Bull. 2006 May;29(5):938-44.Xia X, Pan Y, Zhang WY, Cheng G, Kong LD.State Key Laboratory of Pharmaceutical Biotechnology, Immunobiological Laboratory, Nanjing University, PR China.

 The ethanolic extracts from the rhizome of Curcuma longa L. (turmeric), possesses a wide variety of biological activities related to the treatment and prevention of affective disorders. To study their antidepressant effects, the impacts of chronic mild stress (CMS) and of the subsequent administration of ethanolic extracts of C. longa were investigated. Male Sprague-Dawley rats subjected to the CMS procedure demonstrated increased serum interleukin-6 and tumor necrosis factor-alpha levels, as well as a reduction of natural killer cell activity in splenocytes. In addition, CMS-treated rats exhibited elevated corticotropin-releasing factor in serum and medulla oblongata and cortisol levels in serum, with no significant change in serum adrenocorticotropin hormone levels. The preferential behavior of reduction in sucrose intake was also observed. These findings indicate that the alterations in immune and hypothalamic-pituitary-adrenal (HPA) axis systems could participate in the behavioral response to the CMS procedure in animals. Administration of ethanolic extracts of C. longa largely reversed the above effects. These results demonstrate the antidepressant-like activity of ethanolic extracts of C. longa in the rat CMS model of depression, at least in part by improving the abnormalities in immune and the HPA axis functions.

  Effects of oxygen and turmeric on the formation of oxidative aldehydes in fresh-pack dill pickles.:J Agric Food Chem. 2006 May 3;54(9):3421-7. Cleary K, McFeeters RF.Department of Food Science, North Carolina State University, Box 7624, Raleigh, North Carolina 27695-7624, USA.

 Hexanal, pentanal, and heptanal were found to be normal components of commercially processed, fresh-pack dill pickles. Hexanal and pentanal were present at concentrations severalfold higher than their odor detection thresholds. These aldehydes were also found in pickles that were packed in the laboratory under anaerobic conditions. Injection of oxygen into pickles prepared in anaerobic conditions resulted in the production of increasing the amounts of hexanal, heptanal, and pentanal. Hexanal, pentanal, (E)-2-hexenal, and heptanal levels were negatively correlated with the addition of turmeric in dill pickles with oxygen injected into the jar, indicating that the curcumin present in turmeric is an effective antioxidant in this product. At commercial coloring levels (250 mg/L), turmeric addition maintained aldehyde levels near the concentrations found in commercial fresh-pack pickles packaged in glass containers when oxygen was added in amounts comparable to that which would enter a plastic container during a 1-year storage period. Therefore, the addition of turmeric appears to be an effective approach to minimize the formation of oxidative off-flavors in pasteurized dill pickles that may result from the oxygen permeability of plastic containers.

  Dosage effects of curcumin on cell death types in a human osteoblast cell line.:Food Chem Toxicol. 2006 Aug;44(8):1362-71. Epub 2006 Mar 9.Chan WH, Wu HY, Chang WH.Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan.

 Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties, as well as their ability to either induce or prevent cell apoptosis. However, the precise molecular mechanisms of these effects are unknown. Here, we demonstrate that curcumin can induce apoptotic changes, including JNK activation, caspase-3 activation, and cleavage of PARP and PAK2, at treatment concentrations lower than 25 microM in human osteoblast cells. In contrast, treatment with 50-200 microM of curcumin does not induce apoptosis, but rather triggers necrotic cell death in human osteoblasts. Using the cell permeable dye 2',7'-dichlorofluorescin diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we found that while treatment with 12.5-25 microM curcumin directly increased intracellular oxidative stress, 50-200 microM curcumin had far less effect. Pretreatment of cells with N-acetyl cysteine or alpha-tocopherol, two well known ROS scavengers, attenuated the intracellular ROS levels increases and converted the apoptosis to necrosis induced by 12.5-25 microM curcumin. Moreover, we observed a dose-dependent decrease in intracellular ATP levels after treatment of osteoblast cells with curcumin and pretreatment of cells with antimycin or 2-deoxyglucose to cause ATP depletion significantly converted 12.5-25 microM curcumin-induced apoptosis to necrosis, indicating that ATP (a known mediator of apoptotic versus necrotic death) is most likely involved in the switching mechanism. Overall, our results signify that curcumin dosage treatment determines the possible effect on ROS generation, intracellular ATP levels, and cell apoptosis or necrosis in osteoblast cells.

  Induction of G2/M arrest and inhibition of cyclooxygenase-2 activity by curcumin in human bladder cancer T24 cells.:Oncol Rep. 2006 May;15(5):1225-31.Park C, Kim GY, Kim GD, Choi BT, Park YM, Choi YH.Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Korea. immunpym@pusan.ac.kr

 Curcumin, a polyphenol compound derived from Curcuma longa Linn, has been recognized as a promising anti-cancer drug due to its multiple properties including anti-inflammatory, anti-oxidant and anti-carcinogenic activities. To elucidate the mechanisms by which curcumin inhibits human bladder carcinoma T24 cell proliferation, we tested the effects of curcumin on specific cell cycle pathways and on the expression of cyclooxygenases (COXs). Curcumin inhibited the growth of T24 cells and induced G2/M arrest in a concentration-dependent manner, effects associated with the down-regulation of cyclin A and up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1). However, other G2/M regulatory molecules, such as cyclin A, Cdc2, Cdk2, Wee1 and Cdc25C, were not modulated by curcumin treatment. Furthermore, curcumin decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which correlated with a decrease in prostaglandin E2 (PGE2) synthesis. These observations suggest that curcumin may have therapeutic potential for bladder cancer patients.

  Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis.:J Nat Prod. 2006 Mar;69(3):351-5. Funk JL, Oyarzo JN, Frye JB, Chen G, Lantz RC, Jolad SD, S¨®lyom AM, Timmermann BN.Arizona Center for Phytomedicine Research, Department of Medicine, Department of Cell Biology and Anatomy, University of Arizona, Tucson, 85724, USA. jfunk@u.arizona.edu

 Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of this traditional usage, dietary supplements containing turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding antiarthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well-characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.


  Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells.:Int J Cancer. 2006 Aug 15;119(4):757-64.Beevers CS, Li F, Liu L, Huang S.Department of Biochemistry and Molecular Biology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.

 Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma longa, is undergoing early clinical trials as a novel anticancer agent. However, the anticancer mechanism of curcumin remains to be elucidated. Here we show that curcumin inhibited growth of rhabdomyosarcoma cells (Rh1 and Rh30) (IC50 = 2-5 microM) and arrested cells in G1 phase of the cell cycle. Curcumin also induced apoptosis and inhibited the basal or type I insulin-like growth factor-induced motility of the cells. At physiological concentrations (2.5 microM), curcumin rapidly inhibited phosphorylation of the mammalian target of rapamycin (mTOR) and its downstream effector molecules, p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), in a panel of cell lines (Rh1, Rh30, DU145, MCF-7 and Hela). Curcumin also inhibited phosphorylation of Akt in the cells, but only at high concentrations (>40 microM). The data suggest that curcumin may execute its anticancer activity primarily by blocking mTOR-mediated signaling pathways in the tumor cells.

  Inhibitory effect of cinnamoyl compounds against human malignant cell line.:Indian J Exp Biol. 2006 Mar;44(3):216-20.Indap MA, Radhika S, Motiwale L, Rao KV.Chemotherapy Group, Khanolkar Shodhika, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 208, India.

 In the present study, anti-proliferative effects of dietary polyphenolic compounds have been observed and demonstrated the strong anticancer efficacy of curcumin (CMN), an active constituent of dietary spice (turmeric) using human leukemia cancer cell line. CMN inhibited the proliferation of K562 leukemic cells by induction of apoptosis. The current study demonstrated synergy with combination of drug therapy, and suggested that combination of ferulic acid and cisplatin synergistically inhibited cellular proliferation. Cytotoxic synergy was observed independent of the sequence of addition of two drugs to cultured cells. The synergized growth inhibitory effect with cisplatin was probably associated with G2-M arrest in cell cycle progression. These findings suggested that among the cinnamoyl compounds, CMN was most potent and FER appeared to be a better modulating agent on human malignant cell line.

  Effect of bitter gourd and spent turmeric on constituents of glycosaminoglycans in different tissues in streptozotocin induced diabetic rats.:Mol Cell Biochem. 2006 Jun;286(1-2):53-8. Epub 2006 Mar 11.Kumar GS, Vijayalakshmi B, Salimath PV.Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570 020, India.

 Diet is now one of the well established means in the management of diabetes. Bitter gourd and spent turmeric at 10% level were tested for their efficacy on glycosaminoglycan metabolism in various tissues viz., liver, spleen, lungs, heart and testis in control, diabetic and treated rats. The glycosaminoglycans (GAGs) were isolated from defatted and dried tissues. The contents of sulfated GAGs decreased in all the tissues and the decrease was more prominent in heart and testis. In the isolated GAGs, contents of total sugar, amino sugar, uronic acid and sulfate were studied. Decrease in total sugar content was maximum in testis. Amino sugar content decreased considerably in testis (38%) and lungs (15%). The content of uronic acid also decreased in testis (33%) besides heart (29%) and liver (25%). Sulfate groups in GAGs perform pivotal functions in many biological events and decrease in sulfate content was significant in heart (40%), testis (37%) and liver (37%). GAGs profile on the cellulose acetate electrophoresis revealed that heparan sulfate (HS), hyaluronic acid (HA) and chondroitin sulfate/dermatan sulfate (CS/DS) were present in liver, spleen and lungs. HS, CS were present in heart, DS/CS was observed in testis. The observed beneficial effects in GAGs metabolism during diabetes may be due to the presence of high amounts of dietary fibres present in bitter gourd and spent turmeric, besides, possible presence of bioactive compounds in one or both of them.

  Curcumin analogs as potent aldose reductase inhibitors.:Arch Pharm (Weinheim). 2006 Mar;339(3):123-8. Du ZY, Bao YD, Liu Z, Qiao W, Ma L, Huang ZS, Gu LQ, Chan AS.School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

 In the present study, curcuminoids isolated from curcuma longa were demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone (A(2)), 2,5-bis(3,4-dihydroxybenzylidene)cyclopentanone (B(2)), 1,5-bis(3,4-dihydroxyphenyl)-1,4-pentadiene-3-one (C(2)), and 3,5-bis(3,4-dihydroxybenzylidene)-4-piperidone (D(2)) showed remarkably potent inhibitory effects on aldose reductase with IC(50) of 2.9 microM, 2.6 microM, 3.4 microM, and 4.9 microM, respectively. The structure-activity relationship revealed that the curcumin analogs with ortho-dihydroxyl groups could form a more tight affinity with aldose reductase to exert more potential inhibitory activities.

  Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis.:Mol Carcinog. 2006 May;45(5):320-32.Divya CS, Pillai MR.Department of Molecular Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala, India.

 Curcumin (diferuloyl methane), the major yellow pigment from the rhizomes of turmeric (Curcuma longa Linn), has anticancer properties. Infection with high-risk human papillomaviruses (HPV) leads to development of cervical carcinoma, predominantly through the action of viral oncoproteins E6 and E7.The present study aims at analyzing the antitumor and antiviral properties of curcumin, on HPV associated cervical cancer cells. Our findings indicate curcumin to be cytotoxic to cervical cancer cells in a concentration-dependent and time-dependent manner. The cytotoxic activity was selectively more in HPV16 and HPV18 infected cells compared to non-HPV infected cells. Balance between tumor cell proliferation and spontaneous cell death via apoptosis had an important role in regulation of tumor cell growth. Curcumin-induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. Curcumin also selectively inhibited expression of viral oncogenes E6 and E7, evident from RT-PCR and Western blotting data. Electrophoretic mobility shift assay revealed that activation of NFkappaB-induced by TNFalpha is down regulated by curcumin. Curcumin blocked IkBalpha phosphorylation and degradation, leading to abrogation of NFkappaB activation. Curcumin also down regulated the expression of COX-2, a gene regulated by NFkappaB. Binding of AP-1, an indispensable component for efficient epithelial tissue-specific gene expression of HPV was also selectively down regulated by curcumin. These results provide attractive data for the possible use of curcumin in the management of HPV associated tumors.


  Preventive role of curcumin in lung cancer.:Przegl Lek. 2005;62(10):1180-1. Review. Polish.Balcerek M, Mat?awska I.Katedra i Zak?ad Farmakognozji Collegium Medicum Uniwersytetu Miko?aja Kopernika w Bydgoszczy.

 Carcinogens from cigarette smoke form the link between nicotine addiction and lung cancer, which is the leading cause of cancer-related mortality in the world. One of the most frequently studied chemopreventive agents is a curcumin, a natural compound extracted from turmeric that inhibits cell proliferation and induces apoptosis in human leukaemia, prostate cancer, and non-small cell lung cancer. Curcumin (diferuoylmethane) is a major yellow pigment in turmeric (Curcuma longa) and is widely used as a spice. Curcumin exhibits a variety of pharmacological effects, and has been reported to have anti-inflammatory and anti-tumor activities.

  Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury.:BMC Complement Altern Med. 2006 Feb 19;6:3.Mohanty I, Arya DS, Gupta SK.Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India. ipseetamohanty@yahoo.co.in

 BACKGROUND: In the present investigation, the effect of Curcuma longa (Cl) and Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in an ischemia and reperfusion (I-R) model of myocardial injury. METHODS: Wistar albino rats were divided into four groups and orally fed saline once daily (sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively for 1 month. On the 31st day, in the rats of the control IR, Cl-IR and Os-IR groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for 1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive (+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of pressure decline)} were monitored at pre-set points throughout the experimental duration and subsequently, the animals were sacrificed for immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and histopathological studies. RESULTS: Chronic treatment with Cl significantly reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl demonstrated mitigating effects on several myocardial injury induced hemodynamic {(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic Os treatment resulted in modest modulation of the hemodynamic alterations (MAP, LVEDP) but failed to demonstrate any significant antiapoptotic effects and prevent the histopathological alterations as compared to control IR group. CONCLUSION: In the present study, significant cardioprotection and functional recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the impairment of cardiac performance.

  Use of liquid chromatography-electrospray ionization tandem mass spectrometry to identify diarylheptanoids in turmeric (Curcuma longa L.) rhizome.:J Chromatogr A. 2006 Apr 7;1111(1):21-31. Epub 2006 Feb 21.Jiang H, Timmermann BN, Gang DR.Arizona Center for Phytomedicine Research, College of Pharmacy, University of Arizona, Tucson, 85721, USA.

 LC-ESI-MS/MS coupled to DAD analysis was used as an on-line tool for identification of diarylheptanoids in fresh turmeric rhizome extracts. Based on their mass spectra, from both negative and positive mode LC-ESI-MS/MS analysis, and supported by their DAD spectra, 19 diarylheptanoids were identified. Among these 19 compounds, curcumin, demethoxycurcumin, and bisdemethoxycurcumin were identified by comparing their chromatographic and spectral data with those of authentic standard compounds. The other diarylheptanoid compounds were identified or tentatively identified based on comparison to the three curcuminoids and each other. Twelve of the identified diarylheptanoids have not been previously reported from turmeric and six of these are new compounds.

  Protective effect of curcumin on myocardial ischemia reperfusion injury in rats.:Zhong Yao Cai. 2005 Oct;28(10):920-2. Chinese.Cheng H, Liu W, Ai X.Dept of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan 430071.

 OBJECTIVE: To study the protective effect of curcumin on myocardial reperfusion injury in rats. METHODS: Myocardial ischemia reperfusion injury model was established by occluding the left anterior descending branch of coronary arter for 60 min and removing the ligation later to reperfuse for 60 min in vivo. Different dose of curcumin were administered by intravenous injection 5 min before the onset of ischemia. The changes of myocardial infarct sizes (MIS), the serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH), the myocardial malondialdehyed (MDA) and free fatty acid (FFA) content, the myocardial super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity were measured. RESULTS: Curcumin (20, 40 mg/kg) reduced the myocardial infarct sizes, the serum CK and LDH activity. The myocardial MDA and FFA content all declined. SOD and GSH-Px activity were increased markedly. CONCLUSION: Curcumin exerts protective effects on myocardial ischemia reperfusion injury, which may be due to its function of inhibition of lipid peroxidation, augmentation of endogenous antioxidants and improving myocardial metabolism.

  Curcumin inhibits the proliferation and mineralization of cultured osteoblasts.:Eur J Pharmacol. 2006 Mar 18;534(1-3):55-62. Epub 2006 Feb 14.

 The effects of curcumin, which is an important constituent of rhizomes of the plant Curcuma longa Linn, on the metabolism of osteoblasts were examined in cultures of rat calvarial osteoblastic cells (ROB cells). The proliferation of cells was markedly inhibited upon exposure of cells to curcumin at 5x10(-6) to 1x10(-5) M. Curcumin at 1x10(-5) M did not induce apoptosis in ROB cells but arrested cells at the G1 phase of the cell cycle. In addition, curcumin stimulated the expression of mRNA for p21(WAF1/CIP1), which inhibits the activity of cyclin-dependent kinases, and inhibited the phosphorylation of histone H1. Furthermore, curcumin reduced the rate of deposition of calcium and the formation of mineralized nodules. Our results indicate that curcumin might inhibit the proliferation and mineralization of osteoblastic cells through the expression of p21(WAF1/CIP1).


  Ethnobotany of medicinal plants used by Assamese people for various skin ailments and cosmetics.:J Ethnopharmacol. 2006 Jun 30;106(2):149-57. Epub 2006 Feb 13.Saikia AP, Ryakala VK, Sharma P, Goswami P, Bora U.Department of Biotechnology, Indian Institute of Technology Guwahati, North Guwahati-781039, Assam, India.

 The present paper deals with the medicinal plants used by the people of Assam for curing different skin ailments and for cosmetics. A total of 85 plants belonging to 49 families have been documented for their therapeutic use against skin diseases and as herbal care. The herbal medicines were prepared from various plant parts of single plant, or multiple plants. The majority of the preparation was made using water as the medium. The mode of application was topical, but in many cases it was also administered orally. In several cases the pure herbal preparations was administered along with milk, ghee, honey, coconut oil, curd, etc. Remedies for 18 skin ailments were documented through this study. About 14 plants are known for their use to cure multiple skin diseases. Among these Curcuma longa and Melia azaderach constitute the major plants. The herbal cosmetic products used by the people of Assam ranges from the enhancement of skin colour, hair care, removal of ugly spots, colouring of nails, palms, and teeth. However, many of the plant preparations used for enhancing beauty were also applied for therapeutic use. Herbal remedies were also available for skin burns, prickly heat and pimples. Information on nine plants used for managing dry skin also emerged from this study.

  Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula, on the experimental inflammatory and nociceptive models in rodents.:Biol Pharm Bull. 2006 Feb;29(2):253-60.Zhou H, Wong YF, Cai X, Liu ZQ, Jiang ZH, Bian ZX, Xu HX, Liu L.School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China

 JCICM-6, the extract of an anti-arthritic herbal formula composed of medicinal herbs of Sinomenium acutum, Aconitum carmichaeli DEBX., Curcuma Longa L., Paeonia lactiflora PALL., and Paeonia suffruticosa ANDR., was examined in the effectiveness and mechanism in reducing experimentally-induced inflammation and nociception using nine animal models. JCICM-6 was extracted from herbs and purified with Amberlite XAD-7HP adsorbent resin and analyzed with HPLC-fingerprint for quality consistency. In acute inflammatory models, the paw edema of rats was induced by subcutaneous injection of carrageenan or pro-inflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2) (PGE(2)) into the right hind paws of animals; while the ear edema of mice was induced by applying arachidonic acid or 12-O-tetradecanoylphorbol 13-acetate (TPA) on the ear surface. In nociceptive models, the tail-flick response induced by radiant heat stimulation was measured and the numbers of abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid were recorded. JCICM-6 orally administered in a range of dosages from 0.438 g to 1.75 g/kg significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan or various pro-inflammatory mediators and the ear edema of mice induced by arachidonic acid or TPA. JCICM-6 also significantly prolonged the reaction time of rats to radiant heat stimulation and reduced the numbers of writhing episodes of mice. These results indicated that JCICM-6 possesses significant anti-inflammatory and analgesic effects, which implies that it would be a potential candidate for further investigation as a new anti-arthritic botanical drug for humans.

  Inhibition of telomerase activity and induction of apoptosis by curcumin in K-562 cells:Mutat Res. 2006 Apr 11;596(1-2):81-90. Epub 2006 Jan 30.Chakraborty S, Ghosh U, Bhattacharyya NP, Bhattacharya RK, Roy M.Environmental Carcinogenesis and Toxicology Department, Chittaranjan National Cancer Institute, 37, SP Mukherjee Road, Kolkata 700026, India.

 Telomerase, a reverse transcriptase that maintains telomere length, is highly activated in tumor cells and practically absent in somatic cells and hence considered a potential marker for tumorigenesis. A connection between telomerase activity and resistance to apoptosis has been established. Telomerase, therefore, has been proposed to represent a novel and potentially selective target for cancer therapy. Several synthetic compounds have been developed in recent years with a view to inhibit telomerase activity with telomere shortening below a critical length resulting in apoptosis. Such compounds are always highly toxic. Many plant-derived products act through the induction of apoptosis as a mechanism to suppress carcinogenesis. Curcumin, a phenolic compound isolated from the rhizome of the plant Curcuma longa Linn., has been reported to possess anti-tumor, apoptotic and anti-angiogenic properties. Apoptosis has emerged as the major mechanism by which anti-tumor agents eliminate pre-neoplastic cells or cells progressed to malignancy. The present study was undertaken to examine the mechanism of curcumin-induced apoptosis in human leukemia cell line K-562 with particular emphasis on the role of curcumin on telomerase activity. Induction of apoptosis by curcumin is initiated by the release of cytochrome c from mitochondria into the cytosol, and evidenced by the increase in DNA content in the sub-G1 region as obtained from FACS analysis. Apoptosis is mediated by the activation of caspases 3 and 8, up-regulation of the apoptotic gene bax with concomitant down-regulation of the anti-apoptotic gene bcl-2. Using TRAP assay it has been observed that curcumin inhibits telomerase activity in a dose and time-dependent manner, the inhibition being due to suppression of translocation of telomerase reverse transcriptase (TERT), a catalytic subunit, from cytosol to nucleus. Most significantly, the inhibition of telomerase activity by curcumin correlates with several parameters of apoptosis. The results suggest that telomerase status plays an important role in the induction of apoptosis in K-562 cells by curcumin.

  Menopause: a review on the role of oxygen stress and favorable effects of dietary antioxidants.:Arch Gerontol Geriatr. 2006 May-Jun;42(3):289-306. Epub 2006 Jan 26. Review.Miquel J, Ram¨ªrez-Bosc¨¢ A, Ram¨ªrez-Bosca JV, Alperi JD.Department of Biotechnology, University of Alicante, San Vicente, Ap. 99, E-03080 Alicante, Spain.

 Menopause is often accompanied by hot flashes and degenerative processes such as arteriosclerosis and atrophic changes of the skin that suggest an acceleration of aging triggered by estrogen lack. Therefore, hormone replacement therapy (HRT) has been considered the most suitable treatment for the above symptoms and processes. However, because of the possible serious side effects of HRT (especially the increased risk of thrombo-embolic accidents and breast cancer) there is a growing demand for alternative treatments of the symptoms and pathological processes associated with menopause. In agreement with the above, we review research that supports the concept that oxygen stress contributes to menopause and that some of its physiopathological effects may be prevented and/or treated improving the antioxidant defense of menopausic and postmenopausic women. Accordingly, a selection of micronutrients may be useful as a dietary supplement for protection against the decline of physiological functions caused by age-related oxygen stress. Since aging is accompanied by a progressive oxidation of the physiological sulfur pool, we emphasize the role of the vitamins B that help to maintain the GSH/GSSG ratio in its normal reduced state. Nutritional supplements should also include the key antioxidant vitamins C and E, as well as beta-carotene and the mineral micronutrients found in the oxygen radical-detoxifying enzymes glutathione peroxidase and superoxide dismutase. Moreover, the reviewed data suport the concept that other antioxidants such as lipoic acid and the precursors of glutathione thioproline (TP) and l-2-oxothiazolidine-4-carboxylic acid (OTC), as well as the soy isoflavones and the "coantioxidants" of an hydroalcoholic extract of Curcuma longa may help to prevent antioxidant deficiency with resulting protection of mitochondria against premature oxidative damage with loss of ATP synthesis and especialized cellular functions. Therefore, the administration under medical advice of synergistic combinations of some of the above mentioned antioxidants in the diet as well as topically (for skin protection) may have favorable effects on the health and quality of life of women, especially of those who cannot be treated with HR, suffer high levels of oxygen stress, and do not consume a healthy diet that includes five daily rations of fresh fruit and vegetables.

  Protection by turmeric and myrrh against liver oxidative damage and genotoxicity induced by lead acetate in mice.:Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):32-7.El-Ashmawy IM, Ashry KM, El-Nahas AF, Salama OM.Department of Pharmacology, Faculty of Veterinary Medicine, Alexandria Univerity Research Development, Alexandria, Egypt.

 The effects of lead acetate in the diet (0.5% w/w) on reduced GSH, activity of phase II metabolizing enzyme glutathione S-transferase (GST), lipid peroxidation in liver homogenate and bone marrow chromosomes of mice simultaneously supplemented with powdered turmeric and myrrh for 8 weeks were investigated. Five groups of Swiss male albino mice, each of 30 mice, the first group received a basal diet and served as negative control, the second group received basal diet supplemented with lead acetate only and served as positive control. The other three groups received basal diet supplemented with lead acetate and 1% or 5% turmeric powder and 1% myrrh powder, respectively. Results revealed a significant decrease in the amount of GSH in all treated groups compared with negative control. Also, the activity of GSH S-transferase was significantly decreased in positive control compared with other groups. However, co-administration of the protective plants resulted in a significant increase in the activity of GST compared with both positive and negative control groups. Furthermore, lipid peroxidation was significantly increased in positive control alone, while co-treatment with the protective plants resulted in reduction in the level of lipid peroxidation by 31% and 49% in mice receiving 1% and 5% turmeric powder respectively and 45% in 1% myrrh treated when compared with their respective positive control group. Lead genotoxicity was confirmed through significant reduction in the number of dividing cells, increased total number of aberrant cells and increased frequency of chromosomal aberrations. Simultaneous treatment with these plants significantly reduced the genotoxicity induced by lead administration and the powerful protection was observed with 5% powdered turmeric. It may be concluded that turmeric and myrrh are useful herbal remedies, especially for controlling oxidative damages and genotoxicity induced by lead acetate intoxication.


  Multiple biological activities of curcumin: a short review.:Life Sci. 2006 Mar 27;78(18):2081-7. Epub 2006 Jan 18. Review.Maheshwari RK, Singh AK, Gaddipati J, Srimal RC.Department of Pathology, Uniformed Services University of the Life Sciences, Center for Combat Casualty and Life Sustainment Research, Bethesda, Maryland 20814, USA. maheshwari@usuhs.mil

 Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented for its medicinal properties in Indian and Chinese systems of medicine. It has been widely used for the treatment of several diseases. Epidemiological observations, though inconclusive, are suggestive that turmeric consumption may reduce the risk of some form of cancers and render other protective biological effects in humans. These biological effects of turmeric have been attributed to its constituent curcumin that has been widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result of extensive epidemiological, clinical, and animal studies several molecular mechanisms are emerging that elucidate multiple biological effects of curcumin. This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin.

  Inhibitory effect of Thai plant extracts on P-glycoprotein mediated efflux.:Phytother Res. 2006 Jan;20(1):79-81.Junyaprasert VB, Soonthornchareonnon N, Thongpraditchote S, Murakami T, Takano M.Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayutthaya, Rajathavee, Bangkok 10400, Thailand. pyvbp@mahidol.ac.th

 Curcuminoids from Curcuma longa L. and extracts of Psidium guajava L., Andrographis paniculata (Burm. f.) Nees, Phyllanthus emblica L. and Solanum trilobatum L. were investigated for their inhibitory effect on P-glycoprotein (P-gp) on the efflux transport of rhodamine 123 (Rho-123 ) in Caco-2 cells and rat ileum. Of the five tested samples, curcuminoids and an extract of P. guajava showed the highest inhibitory effect on P-gp mediated efflux of Rho-123 in Caco-2 cells. Additionally, they were found to have equal potential in inhibiting Rho-123 efflux transport from serosal to mucosal surfaces of the rat ileum.

  An efficient protocol for genetic transformation and shoot regeneration of turmeric (Curcuma longa L.) via particle bombardment.:Plant Cell Rep. 2006 Mar;25(2):112-6. Epub 2006 Jan 6.Shirgurkar MV, Naik VB, von Arnold S, Nadgauda RS, Clapham D.Tissue Culture Pilot Plant, National Chemical Laboratory, Dr. Homi Bhabha Road, Pashan, Pune 411008, India.

 Turmeric (Curcuma longa L.) is an important spice crop plant that is sterile and cannot be improved by conventional breeding. An efficient method for stable transformation for turmeric, C. longa L., was developed using particle bombardment. Callus cultures initiated from shoots were bombarded with gold particles coated with plasmid pAHC25 containing the bar and gusA genes each driven by the maize ubiquitin promoter. Transformants were selected on medium containing glufosinate. Transgenic lines were established on selection medium from 50% of the bombarded calluses. Transgenic shoots regenerated from these were multiplied and stably transformed plantlets were produced. Polymerase chain reaction (PCR) and histochemical GUS assay confirmed the stable transformation. Transformed plantlets were resistant to glufosinate.

  Curcumin: getting back to the roots.:Ann N Y Acad Sci. 2005 Nov;1056:206-17.Shishodia S, Sethi G, Aggarwal BB.Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

 The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."

  Alpha-glucosidase inhibition of natural curcuminoids and curcumin analogs.:Eur J Med Chem. 2006 Feb;41(2):213-8. Epub 2006 Jan 4.Du ZY, Liu RR, Shao WY, Mao XP, Ma L, Gu LQ, Huang ZS, Chan AS.School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

 Natural curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) isolated from Curcuma longa (turmeric), and synthetic curcumin analogs (A(1-7), B(1-7), C(1-6) and D(1-7)) were evaluated in vitro for the alpha-glucosidase inhibitory activity via UV and circular dichroism (CD) spectroscopy. The results indicated that natural curcuminoid compound 3 showed a remarkable inhibitory effect with IC(50) of 23.0 microM, and the synthetic compounds A(2), B(2), C(2) and D(2) showed potent inhibitory effects with IC(50) of 2.8, 2.6, 1.6 and 8.2 microM, respectively. Kinetic study exhibited that the mechanism of alpha-glucosidase inhibition of both 3 and C(2) was non-competitive. The structure activity relationship revealed that the ortho dihydroxyl groups could form a more tight interaction with alpha-glucosidase to exert more potential inhibitory activities.


  Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells.:Cell Biol Int. 2006 Mar;30(3):221-6. Epub 2005 Dec 22.Shi M, Cai Q, Yao L, Mao Y, Ming Y, Ouyang G.Key Laboratory of China Education Ministry for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, China.

 Curcumin, an active ingredient from the rhizome of the plant, Curcuma longa, has antioxidant, anti-inflammatory and anti-cancer activities. It has recently been demonstrated that the chemopreventive activities of curcumin might be due to its ability to inhibit cell growth and induce apoptosis. In the present study, we have investigated the effects of curcumin on growth and apoptosis in the human ovarian cancer cell line Ho-8910 by MTT assay, fluorescence microscopy, flow cytometry and Western blotting. Our data revealed that curcumin could significantly inhibit the growth and induce apoptosis in Ho-8910 cells. A decrease in expression of Bcl-2, Bcl-X(L) and pro-caspase-3 was observed after exposure to 40 microM curcumin, while the levels of p53 and Bax were increased in the curcumin-treated cells. These activities may contribute to the anticarcinogenic action of curcumin.

  A comparison of the antimicrobial activity of garlic, ginger, carrot, and turmeric pastes against Escherichia coli O157:H7 in laboratory buffer and ground beef..:Foodborne Pathog Dis. 2005 Winter;2(4):330-40.Gupta S, Ravishankar S.National Center for Food Safety and Technology, Illinois Institute of Technology, Summit-Argo, Illinois 60501, USA.

 The antimicrobial effects of garlic, ginger, carrot and turmeric pastes against Escherichia coli O157:H7 in laboratory buffer and model food system were investigated. Turmeric paste, fresh carrot, ginger and garlic pastes from roots, and commercial ginger and garlic paste were heated alone or with buffered peptone water (BPW) or ground beef at 70 degrees C for 7 min. All samples were inoculated with a three strain cocktail of overnight cultures of E. coli O157: H7 and stored at 4 degrees C and 8 degrees C for 2 weeks. Each paste exhibited different antimicrobial effects alone and in ground beef or BPW at 4 degrees C and 8 degrees C for 2 weeks. Commercial ginger paste and fresh garlic paste showed the strongest antimicrobial activity with complete inactivation of E. coli O157:H7 in the paste at 3 days at 4 degrees C and 8 degrees C. Carrot and turmeric pastes did not show any antimicrobial activity both at 4 degrees C and 8 degrees C. Commercial garlic showed antimicrobial activity at both 4 degrees C and 8 degrees C (about 1 log CFU/g reduction) in the paste. However, fresh ginger paste showed antimicrobial activity only at 8 degrees C. Only commercial ginger paste had antimicrobial activity in BPW at 4 degrees C for 2 weeks. However, commercial ginger paste showed antimicrobial activity in ground beef at 3 days and after (about 1-2 log CFU/g) compared to control samples at 8 degrees C for 2 weeks. Fresh garlic paste showed antimicrobial activity only in BPW (1.3 log CFU/g) at 8 degrees C. These results indicate that the antimicrobial activity of these pastes is decreased in ground beef and laboratory buffer.

  Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia.:Biochem Biophys Res Commun. 2006 Feb 10;340(2):359-68. Epub 2005 Dec 13.Rajasingh J, Raikwar HP, Muthian G, Johnson C, Bright JJ.Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.

 Adult T cell leukemia is an aggressive and frequently fatal malignancy that expressess constitutively activated growth-signaling pathways in association with deregulated growth and resistance to apoptosis. Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma longa that has traditionally been used in the treatment of injury and inflammation. But the effect and mechanism of action of curcumin on T cell leukemia is not known. To investigate the antitumor activity of curcumin in T cell leukemia, we examined its effect on constitutive phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2, HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and STAT5 signaling proteins. In vitro treatment with curcumin induced a dose-dependent decrease in JAK and STAT phosphorylation resulting in the induction of growth-arrest and apoptosis in T cell leukemia. The induction of growth-arrest and apoptosis in association with the blockade of constitutively active JAK-STAT pathway suggests this be a mechanism by which curcumin induces antitumor activity in T cell leukemia.

  Plant foods in the management of diabetes mellitus: spices as beneficial antidiabetic food adjuncts.:Int J Food Sci Nutr. 2005 Sep;56(6):399-414. Review.Srinivasan K.Department of Biochemistry & Nutrition, Central Food Technological Research Institute, Mysore-570013, India.

 Diet has been recognized as a corner stone in the management of diabetes mellitus. Spices are the common dietary adjuncts that contribute to the taste and flavour of foods. Besides, spices are also known to exert several beneficial physiological effects including the antidiabetic influence. This review considers all the available information from animal experimentation as well as clinical trials where spices, their extracts or their active principles were examined for treatment of diabetes. Among the spices, fenugreek seeds (Trigonella foenumgraecum), garlic (Allium sativum), onion (Allium cepa), and turmeric (Curcuma longa) have been experimentally documented to possess antidiabetic potential. In a limited number of studies, cumin seeds (Cuminum cyminum), ginger (Zingiber officinale), mustard (Brassica nigra), curry leaves (Murraya koenigii) and coriander (Coriandrum sativum) have been reported to be hypoglycaemic.

  Curcuma longa extract protects against gastric ulcers by blocking H2 histamine receptors.:Biol Pharm Bull. 2005 Dec;28(12):2220-4.Kim DC, Kim SH, Choi BH, Baek NI, Kim D, Kim MJ, Kim KT.Division of Molecular and Life Science, SBD-NCRC, Pohang University of Science and Technology, South Korea.

 Curcuma longa has been commonly used as a traditional remedy for a variety of symptoms such as inflammation, gastritis and gastric ulcer. When C. longa extract was administered per os to pylori-ligated rat stomachs, it reduced gastric acid secretion and protected against the formation of gastric mucosal lesions. We therefore tested whether C. longa extract inhibits gastric ulcers by blocking the H(2) histamine receptor. Dimaprit, a H(2) histamine receptor agonist, induced intracellular cAMP production in U937 and HL-60 promyelocytes. Pretreatment with C. longa extract significantly blocked dimaprit-induced cAMP production in a concentration dependent manner, but had no effect on the elevation of cAMP levels triggered by isoproterenol-induced beta(2)-adrenoceptor activation in U937 cells. To identify the active component(s) of C. longa extract, we sequentially fractionated it by extraction with ethyl acetate, n-butanol and water. We found that the ethyl acetate extract showed the most potent H(2)R antagonistic effect against dimaprit-induced cAMP production. However, curcumin, a major component of C. longa extract, showed no H(2)R blocking effect. C. longa ethanol extract and ethylacetate extract also blocked the binding of [(3)H]-tiotidine to membrane receptors on HL-60 cells. These findings suggest that the extract from C. longa specifically inhibits gastric acid secretion by blocking H(2) histamine receptors in a competitive manner.


  Turmeric (Curcuma longa) rhizome paste and honey show similar wound healing potential: a preclinical study in rabbits.:Int J Low Extrem Wounds. 2005 Dec;4(4):205-13.Kundu S, Biswas TK, Das P, Kumar S, De DK.Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata, India. vetsubu@yahoo.com

 The potential efficacy of fresh turmeric (Curcuma longa) paste to heal wounds was tested in a preclinical study in an animal model. Turmeric paste was compared with honey as a topical medicament against a control on experimentally created full-thickness circular wounds in 18 rabbits (Oryctolagous cuniculus). Wound healing was assessed on the basis of physical, histomorphological, and histochemical parameters on treatment days 0, 3, 7, and 14. Only tensile strength was measured on day 14 of treatment. It was observed that the wound healing was statistically significantly faster (P < .01) in both treatment groups compared to the control group.

  Curcuma longa L. constituents inhibit sortase A and Staphylococcus aureus cell adhesion to fibronectin.:J Agric Food Chem. 2005 Nov 16;53(23):9005-9.Park BS, Kim JG, Kim MR, Lee SE, Takeoka GR, Oh KB, Kim JH.School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, South Korea.

 The inhibitory activity of Curcuma longa L. (turmeric) rhizome constituents against sortase A, a bacterial surface protein anchoring transpeptidase, from Staphylococcus aureus ATCC 6538p was evaluated. The activity of the isolated compounds (1-4) was compared to that of the positive control,p-hydroxymecuribenzoic acid (pHMB). The biologically active components of C. longa rhizome were characterized by spectroscopic analysis as the curcuminoids curcumin (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3). Curcumin was a potent inhibitor of sortase A, with an IC50 value of 13.8 +/- 0.7 microg/mL. Bisdemethoxycurcumin (IC50 = 31.9 +/- 1.2 microg/mL) and demethoxycurcumin (IC50 = 23.8 +/- 0.6 microg/mL) were more effective than pHMB (IC50 = 40.6 +/- 1.2 microg/mL). The three isolated compounds (1-3) showed no growth inhibitory activity against S. aureus strain Newman, with minimum inhibitory concentrations (MICs) greater than 200 microg/mL. Curcumin also exhibited potent inhibitory activity against S. aureus cell adhesion to fibronectin. The suppression of fibronectin-binding activity by curcumin highlights its potential for the treatment of S. aureus infections via inhibition of sortase activity. These results indicate that curcumin is a possible candidate in the development of a bacterial sortase A inhibitor.

  Prevention of kainic acid-induced changes in nitric oxide level and neuronal cell damage in the rat hippocampus by manganese complexes of curcumin and diacetylcurcumin.:Life Sci. 2006 Mar 13;78(16):1884-91. Epub 2005 Nov 2.

 Curcumin is a natural antioxidant isolated from the medicinal plant Curcuma longa Linn. We previously reported that manganese complexes of curcumin (Cp-Mn) and diacetylcurcumin (DiAc-Cp-Mn) exhibited potent superoxide dismutase (SOD)-like activity in an in vitro assay. Nitric oxide (NO) is a free radial playing a multifaceted role in the brain and its excessive production is known to induce neurotoxicity. Here, we examined the in vivo effect of Cp-Mn and DiAc-Cp-Mn on NO levels enhanced by kainic acid (KA) and L-arginine (L-Arg) in the hippocampi of awake rats using a microdialysis technique. Injection of KA (10 mg/kg, i.p.) and L-Arg (1000 mg/kg, i.p.) significantly increased the concentration of NO and Cp-Mn and DiAc-Cp-Mn (50 mg/kg, i.p.) significantly reversed the effects of KA and L-Arg without affecting the basal NO concentration. Following KA-induced seizures, severe neuronal cell damage was observed in the CA1 and CA3 subfields of hippocampal 3 days after KA administration. Pretreatment with Cp-Mn and DiAc-Cp-Mn (50 mg/kg, i.p.) significantly attenuated KA-induced neuronal cell death in both CA1 and CA3 regions of rat hippocampus compared with vehicle control, and Cp-Mn and DiAc-Cp-Mn showed more potent neuroprotective effect than their parent compounds, curcumin and diacetylcurcumin. These results suggest that Cp-Mn and DiAc-Cp-Mn protect against KA-induced neuronal cell death by suppression of KA-induced increase in NO levels probably by their NO scavenging activity and antioxidative activity. Cp-Mn and DiAc-Cp-Mn have an advantage to be neuroprotective agents in the treatment of acute brain pathologies associated with NO-induced neurotoxicity and oxidative stress-induced neuronal damage such as epilepsy, stroke and traumatic brain injury.

  Antimicrobial effect of Thai spices against Listeria monocytogenes and Salmonella typhimurium DT104.:J Food Prot. 2005 Oct;68(10):2054-8.Thongson C, Davidson PM, Mahakarnchanakul W, Vibulsresth P.Department of Food Science and Technology, 2605 River Drive, University of Tennessee, Knoxville, Tennessee 37996-4591, USA.

 The objective of this study was to determine the potential antimicrobial activity of extracts and essential oils of spices from Thailand against foodborne pathogenic bacteria. The antimicrobial efficacy of ginger (Zingiber officinale), fingerroot (Boesenbergia pandurata), and turmeric (Curcuma longa) was evaluated against five strains of Listeria monocytogenes and four strains of Salmonella enterica ssp. enterica serovar Typhimurium DT104. Antimicrobial activity was investigated in microbiological media by using an agar dilution assay and enumeration over time and a model food system, apple juice, by monitoring growth over time. In the agar dilution assay, water extracts of the three spices had no effect on L. monocytogenes. Similarly, 50% ethanol extracts of ginger or turmeric had no effect. In contrast, ethanolic fingerroot extracts at 5 to 10% (vol/ vol) inhibited most L. monocytogenes strains for 24 h in the agar dilution assay. Commercial essential oils (EO) of ginger or turmeric inhibited all L. monocytogenes at < or = 0.6 or < or = 10%, respectively. Fingerroot EO inhibited all strains at < or = 0.4%. In the enumeration-over-time assay, a 5% fingerroot ethanol extract reduced ca. 4 log CFU/ml Listeria by around 2 log in 24 h while 10% inactivated the microorganism in 9 h. Fingerroot EO at 0.2% inactivated 4 log CFU/ml L. monocytogenes in 6 to 9 h. Neither extracts nor commercial EO had any effect on Salmonella Typhimurium DT 104 with the exception of fingerroot EO, which inhibited all strains at < or = 0.7%. Addition of 0.2% fingerroot EO to apple juice reduced 4 log of L. monocytogenes Scott A and both strains of Salmonella Typhimurium to an undetectable level within 1 to 2 days. It was concluded that fingerroot EO and extract have potential for inhibiting pathogens in food systems.

  Assessing the quality of RCTs on the effect of beta-elemene, one ingredient of a Chinese herb, against malignant tumors.:Contemp Clin Trials. 2006 Feb;27(1):70-82. Epub 2005 Oct 21.Peng X, Zhao Y, Liang X, Wu L, Cui S, Guo A, Wang W.School of the Public Health and Family Medicine, Capital University of Medical Sciences, Beijing 100054, China.

 OBJECTIVE: To evaluate the quality of randomized controlled trials (RCTs) for Elemene injections, one ingredient of Chinese herb Curcuma wenyujin, for malignant tumors widely used in clinical practice in China. METHODS: We used a systematic sample of 127 reports of RCTs that used Elemene injections as an intervention. The quality of each report was assessed using the number of Consolidated Standards for Reporting of Trials (CONSORT) checklist items included, the frequency of allocation concealment and a 5-point quality assessment instrument (Jadad). RESULTS: 69.44% of the CONSORT checklist items was included in the reports. Only 2 (1.57%) RCTs reported allocation concealment by sealed envelopes. 123 (96.85%) reports described baseline demographic and clinical characteristics of each group. But only 5 (3.94%) of 127 RCTs reported statistics analysis results of baseline data. None of the reports stated in the methods section that intention-to-treat (ITT) analysis was used, although 111 (87.40%) reports described the number of participants (denominator) in each group included in each analysis. Information regarding adverse events was reported in 83.46% of the RCTs. However the quality of reports were low as assessed by the Jadad scale. CONCLUSIONS: The methodological quality of RCTs of Elemene injection against malignant tumors was low. Therefore, the effect of Elemene injection being used in clinical settings needs to be confirmed by further RCTs. Meanwhile, there is a need to supervise and urge researchers in China to conform to Good Clinical Practice (GCP) and CONSORT guidelines when reporting.


  Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation.:Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):85-90. Epub 2005 Oct 20.Yang X, Thomas DP, Zhang X, Culver BW, Alexander BM, Murdoch WJ, Rao MN, Tulis DA, Ren J, Sreejayan N.Division of Pharmaceutical Sciences, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071-3375, USA.

 OBJECTIVE: Vascular smooth muscle cell (VSMC) migration, proliferation, and collagen synthesis are key events involved in the pathogenesis of cardiovascular disease. Growth factors, such as platelet-derived growth factor (PDGF) and fibroblast growth factor, released during vascular injury plays a pivotal role in regulating these events. Curcumin (diferuloyl methane), a major component of the spice turmeric (Curcuma longa), has been shown recently to have beneficial effects in chronic conditions, such as inflammation, cancer, cystic fibrosis, and Alzheimer's disease. The objective of this study was to investigate the ability of curcumin to inhibit PDGF-stimulated migration, proliferation, and collagen synthesis in cultured VSMCs and neointima formation after carotid artery injury in rats. METHODS AND RESULTS: Curcumin (1 to 25 microM) produced a concentration-dependent inhibition of PDGF-elicited VSMC migration, proliferation, and collagen synthesis assessed by chemotaxis, [3H]thymidine incorporation, and [3H]-L-proline incorporation, respectively. Curcumin blocked PDGF-induced VSMC actin-cytoskeleton reorganization, attenuated PDGF signal transduction, and inhibited the binding of PDGF to its receptors. Carotid artery neointima formation was significantly attenuated by perivascular curcumin compared with vehicle controls 14 days after injury, characterized by reduced DNA synthesis, collagen synthesis, and PDGF receptor phosphorylation. CONCLUSIONS: These data suggest that curcumin is a potent inhibitor of key PDGF-stimulated VSMC functions and may play a critical role in regulating these events after vascular injury.

  Growth inhibitory activities of crude extracts obtained from herbal plants in the Ryukyu Islands on several human colon carcinoma cell lines:Asian Pac J Cancer Prev. 2005 Jul-Sep;6(3):353-8.

 There is increasing interest in the use of herbs for the treatment of human diseases including cancer. Therefore, the purpose of this study was to determine whether crude extracts obtained from 44 herbal plants in the Ryukyu Islands might contain components capable of inhibiting the growth of a variety of human colon carcinoma cell lines. Leaves, roots and other parts of the plants were extracted with chloroform, and the crude extracts were dissolved in dimethylsulfoxide and used for the experiments. Extracts of Hemerocallis fulva, Ipomoea batatas, Curcuma longa, and Nasturium officinale caused marked dose-dependent growth inhibition, with IC(50) values in the range of 10-80 mug/ml. With the HCT116 cell line, the extracts of Hemerocallis fulva and Ipomoea batatas induced G1 cell cycle arrest after 48 h of treatment. In addition, we found that extracts of Curcuma longa, and Nasturium officinale induced apoptosis in these cells after 48 h of treatment. The present studies are the first systematic examination of the growth inhibitory effects of crude extracts obtained from herbal plants in the Ryukyu Islands. The findings provide evidence that several plants in the Ryukyu Islands contain components that may have anticancer activity.

  Radioprotection of turmeric extracts in bacterial system.:Acta Biol Hung. 2005;56(3-4):333-43.Pal A, Pal AK.Biophysics Division, Saha Institute of Nuclear Physics, 37, Belgachia Road, Kolkata-700 037, India.

 The present study investigates the possible role of crude turmeric extracts in radioprotection by a variety of methods. Although curcumin, the main bioactive component of turmeric, has been extensively used in such studies, the efficiency of the crude extracts has been poorly investigated. This study revealed that dimethyl sulfoxide (DMSO) extracts of turmeric produces a significant amount of radioprotection, which is very similar in nature and extent to that imparted by curcumin. Field Inversion Gel Electrophoresis (FIGE) studies also clearly showed the protection offered by turmeric extracts against X-ray induced DNA damage of E. coli WP2s(lambda) cells.

  Solid-phase microextraction-gas chromatographic-mass spectrometric analysis of volatile compounds from Curcuma wenyujin Y.H. Chen et C. Ling.:J Pharm Biomed Anal. 2006 Feb 24;40(3):552-8. Epub 2005 Sep 21.Cao J, Qi M, Fang L, Zhou S, Fu R, Zhang P.Department of Chemistry, School of Science, Beijing Institute of Technology, Beijing 100081, China.

 A solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS) for analysis of the volatile compounds from Curcuma wenyujin Y.H. Chen et C. Ling is described. SPME parameters (fiber type, extraction temperature and time, headspace volume and desorption time) and GC conditions were tested. The powdered sample of C. wenyujin Y.H. Chen et C. Ling was directly analyzed by SPME-GC-MS and 72 compounds were identified. The results from SPME-GC-MS were compared with those obtained from steam distillation gas chromatography-mass spectrometry (SD-GC-MS) with a good agreement. The results show that SPME-GC-MS method is a fast, simple and efficient way for the analysis of volatile components from traditional Chinese medicines (TCMs).

  Efficiency of foam fractionation for the enrichment of nonpolar compounds from aqueous extracts of plant materials.:J Nat Prod. 2005 Sep;68(9):1386-9.Backleh-Sohrt M, Ekici P, Leupold G, Parlar H.Technical University of Munich, Department of Chemical-Technical Analysis and Chemical Food Technology, Weihenstephaner Steig 23, D-85354 Freising-Weihenstephan, Germany.

 Biologically active compounds from several useful plants were enriched using foam fractionation, a separatory method belonging to the adsorptive bubble separation (ABS). Nonpolar humulones (1-6) from Pilsener beer, curcuminoids (7-9) from turmeric, and carotenoids (16 and 17) from carrot juice were enriched fast and quantitatively, depending on the process parameters, whereas more polar compounds such as catechins from green tea (11, 12, 14, and 15) and naringin (18) and hesperidin (19) from orange and grapefruit juices could not be enriched.


  Herbal medicine with curcuma and fumitory in the treatment of irritable bowel syndrome: a randomized, placebo-controlled, double-blind clinical trial.:Scand J Gastroenterol. 2005 Aug;40(8):936-43.Brinkhaus B, Hentschel C, Von Keudell C, Schindler G, Lindner M, St¨¹tzer H, Kohnen R, Willich SN, Lehmacher W, Hahn EG.Institute of Social Medicine, Epidemiology, and Health Economics, Charit¨¦ University Medical Center, Luisenstr. 57, DE-10098 Berlin, Germany. benno.brinkhaus@charite.de

 OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder for which there is no reliable medical treatment. The aim of this study was to determine the efficacy of two herbal remedies used in the treatment of IBS. MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled trial, IBS patients were randomly assigned to one of three treatment groups: 1) Curcuma xanthorriza 60 mg daily (curcuma group) (n=24), 2) Fumaria officinalis 1500 mg daily (fumitory group) (n=24) and 3) placebo (n=58). The study treatment was applied three times a day for 18 weeks. The main outcome parameters were changes in global patient ratings of IBS-related pain and distension on a visual analogue scale (0-50 mm) between baseline and at the end of treatment. Additional outcome parameters included global assessments of changes in IBS symptoms and psychosocial stress caused by IBS. RESULTS: A total of 106 patients (mean age 48+/-12 years, 63% F) were included in the intention-to-treat group. IBS-related pain decreased by -0.9+/-11.5 (mm+/-SD) in the fumitory group, -0.3+/-9.9 in the placebo group and increased by 2.0+/-9.5 in the curcuma group (p=0.81). IBS-related distension decreased by -1.4+/-12.5 in the curcuma group, -2.1+/-9.2 in the placebo group and increased by 0.3+/-9.3 in the fumitory group (p=0.48). Additionally, the global assessment of changes in IBS symptoms and psychological stress due to IBS did not differ significantly among the three treatment groups. CONCLUSIONS: Neither fumitory nor curcuma showed any therapeutic benefit over placebo in patients with IBS. Therefore, the use of these herbs for the treatment of IBS cannot be recommended.

  Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats:Pharmacol Biochem Behav. 2005 Sep;82(1):200-6.Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ.Department of Pharmacology, School of Basic Medical Science, Peking University, China.

 Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicinal formula, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and we hypothesized that curcumin would have an influence on depressive-like behaviors. The purpose of the present study was to confirm the putative antidepressant effect of chronic administrations of curcumin (1.25, 2.5, 5 and 10 mg/kg, p.o.) in the forced swimming test and bilateral olfactory bulbectomy (OB) models of depression in rats. In the first study, chronic treatment with curcumin (14 days) reduced the immobility time in the forced swimming test. In the second experiment, curcumin reversed the OB-induced behavioral abnormalities such as hyperactivity in the open field, as well as deficits in step-down passive avoidance. In addition, OB-induced low levels of serotonin (5-HT), noradrenaline (NA), high 5-hydroxyindoleacetic acid (5-HIAA) and 4-dihydroxyphenylacetic acid (DOPAC) in the hippocampus were observed, and were completely reversed by curcumin administration. A slight decrease in 5-HT, NA and dopamine (DA) levels was found in the frontal cortex of OB rats which was also reversed by curcumin treatment. These results confirm the antidepressant effects of curcumin in the forced swim and the OB models of depression in rats, and suggest that these antidepressant effects may be mediated by actions in the central monoaminergic neurotransmitter systems.

  Antibacterial activity of Curcuma longa L. against methicillin-resistant Staphylococcus aureus.:Phytother Res. 2005 Jul;19(7):599-604. Kim KJ, Yu HH, Cha JD, Seo SJ, Choi NY, You YO.Department of Oral Microbiology, School of Dentistry and WBMI, Wonkwang University, Iksan, South Korea.

 Methicillin-resistant Staphylococcus aureus (MRSA) has been emerging worldwide as one of the most important hospital and community pathogens. Therefore, new agents are needed to treat MRSA associated infections. The present study investigated the antimicrobial activity of ethyl acetate, methanol and water extracts of Curcuma longa L. (C. longa) against MRSA. The ethyl acetate extract of C. longa demonstrated a higher antibacterial activity than the methanol extract or water extract. Since the ethyl acetate extract was more active than the other extracts, the study examined whether the ethyl acetate extract could restore the antibacterial activity of beta-lactams and alter the MRSA invasion of human mucosal fibroblasts (HMFs). In the checkerboard test, the ethyl acetate extract of C. longa markedly lowered the MICs of ampicillin and oxacillin against MRSA. In the bacterial invasion assay, MRSA intracellular invasion was significantly decreased in the presence of 0.125-2 mg/mL of C. longa extract compared with the control group. These results suggest that the ethyl acetate extract of C. longa may have antibacterial activity and the potential to restore the effectiveness of beta-lactams against MRSA, and inhibit the MRSA invasion of HMFs.

  Effect of curcumin on caspase 8- and caspase 9- induced apoptosis of lymphoma Raji cell.:Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Aug;13(4):624-7. Chinese.Wu Q, Chen Y, Li XG.Institute of Hematology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.

 Curcumin is a crucial component of curcuma. Recently more attention has been paid to the effect of curcumin on specific proliferative inhibition and inducing apoptosis of tumor cells. This study was aimed to investigate the anticancer activities of curcumin and its molecular mechanism. Raji cells (lymphoma cell line) were selected as studying targets, peripheral blood mononuclear cells (PBMNC) obtained from healthy donors were separated by Ficoll solution and suspended in RMPI 1640. The inhibition rates of Raji cells and PBMNC after treatment with curcumin at various concentrations and different times were determined by MTT method and were compared. The expressions of caspase 8 and caspase 9 in Raji cells after treatment with curcumin at 25 micromol/L (IC(50)) and for 24 hours were detected by Western blot. The results showed that curcumin could inhibit proliferation of Raji cells in dose-and time-dependent manner. Curcumin could remarkablely enhance the Raji cell apoptosis at 25 micromol/L and 24 hours (P < 0.01), and its effect was dose-dependent and time-selective. Curcumin had no remarkable effect on PBMNC at certain concentrations, which demonstrated that curcumin could selectively inhibit tumor cell proliferation. It is concluded that the expression of caspase 8 and caspase 9 plays an important role in the proliferation and apoptosis of Raji cells, so that curcumin showed inhibitive effect on Raji cells at various concentrations.

  Laboratory study of effects of yifuning soft capsules on postmenopausal osteoporosis.:Zhongguo Zhong Yao Za Zhi. 2005 Jun;30(12):919-22. Chinese.Liang L, Deng HZ.Department of Chinese Traditional Medicine, Nanfang Medicine University, Guangzhou 510515, China.

 OBJECTIVE: To study the effects of Yifuning soft capsules on postmenopausal osteoporosis in ovariectomized female rats. METHOD: 60 female sprague-dawley rats in 3-month were used, 50 of them were ovariectomized and randomly divided into 5 groups: ovariectomy (OVX), OVX with diethylstilbestrol tables (DT), OVX with YFN (high dose, middle dose and low dose), the others were sham-operated group. Began to give the rats drugs in the fifth week after the operation. After 12 weeks killed the rats. The blood,the uterus and bones were collected to inspect. The content of estrogen (E2) in serum was detected by radioimmunoassay method. The contents of Ca, P, ALP in serum were detected using the automic biochemistry-analyse device. The uterus were weight and the length, width, dry weight and net weight of the shoulder bone were measured. The contents of Ca, Mg, Zn, Mn in the bone were measured using the automic absorption spectrophotometer. The right femer and the third lumbar vertebra were detected for BMD using the dual-energy X-ray absorptiometry scanner and compression test using electronic testing device. RESULT: After using the drugs,the content of E2, Ca in serum, the weight of uterus, the contents of Ca, Mg, Zn, Mn in the bone and the BMD of right femer increased significantly, the content of P, ALP in serum decreased significantly. CONCLUSION: Yifuning soft capsules has a good effect on postmenopausal osteoporosis, which provides evidence for clinical use.


  Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.:J Med Food. 2005 Summer;8(2):256-60.Rukkumani R, Aruna K, Varma PS, Rajasekaran KN, Menon VP.Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.

 Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural principles and their analogs are known to possess anti-hyperlipidemic properties. In the present work we tested the effect of curcumin, an active principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced hyperlipidemia. Male albino Wistar rats were used for the experimental study. Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs), and free fatty acids (FFAs). The results showed that the levels of cholesterol, TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and alcohol + deltaPUFA-treated groups, which were brought down significantly on treatment with either of the curcuminoids. Curcumin analog treatment was found to be more effective than curcumin treatment. From the results obtained, we conclude that both curcumin and its analog effectively protect the system against alcohol- and deltaPUFA-induced hyperlipidemia and are possible candidates for the treatment of hyperlipidemia.

  Antiplatelet property of Curcuma longa L. rhizome-derived ar-turmerone.:Bioresour Technol. 2006 Aug;97(12):1372-6. Epub 2005 Aug 19.Lee HS.Faculty of Applied Biotechnology, Research Center for Industrial Development of Biofood Materials, College of Agriculture, Chonbuk National University, Chonju 561-756, Republic of Korea. hoiseon@chonbuk.ac.kr

 The antiplatelet activities of Curcuma longa L. rhizome-derived materials were measured using a platelet aggregometer and compared with those of aspirin as antiplatelet agent. The active constituent from the rhizome of Curcuma longa L. was isolated and characterized as ar-turmerone by various spectral analyses. At 50% inhibitory concentration (IC50) value, ar-turmerone was effective in inhibiting platelet aggregation induced by collagen (IC50, 14.4 microM) and arachidonic acid (IC50, 43.6 microM). However, ar-turmerone had no effect on platelet activating factor or thrombin induced platelet aggregation. In comparison, ar-turmerone was significantly more potent platelet inhibitor than aspirin against platelet aggregation induced by collagen. These results suggested that ar-turmerone could be useful as a lead compound for inhibiting platelet aggregation induced by collagen and arachidonic acid.

  Effect of Dianex, a herbal formulation on experimentally induced diabetes mellitus.:Phytother Res. 2005 May;19(5):409-15.Mutalik S, Chetana M, Sulochana B, Devi PU, Udupa N.College of Pharmaceutical Sciences, Manipal, Karnataka, India.

 Dianex, a polyherbal formulation consisting of the aqueous extracts of Gymnema sylvestre, Eugenia jambolana, Momordica charantia Azadirachta indica, Cassia auriculata, Aegle marmelose, Withania somnifera and Curcuma longa was screened for hypoglycemic activity in normal and streptozotocin induced diabetic mice. Dianex was administered in different doses of 100-500 mg/kg/day orally in acute (6 h) and long-term (6 weeks) studies. Blood glucose levels were checked 2-6 h after treatment in acute studies and every 2 weeks in long-term studies. Body weight was recorded on the first and final day of the treatment in the long-term studies with diabetic mice. After 6 weeks, high-density lipoprotein, triglycerides, total cholesterol, alanine transaminase (ALT), aspertate transaminase (AST), urea and creatinine were estimated in serum of the diabetic mice. Glycogen and total protein levels were estimated in the liver. Also, the liver and pancreas was subjected to histological examination. Oral glucose tolerance and in vitro free radical scavenging activity was also studied.Dianex produced significant (p<0.05) hypoglycemic activity at 250-500 mg/kg doses in both normal and diabetic mice in acute and long-term studies. The body weight of diabetic mice significantly (p<0.05) increased with all tested doses of Dianex. The elevated triglycerides, cholesterol, ALT, AST, urea and creatinine levels in diabetic mice were significantly (p<0.05) reduced at the doses of 250 and 500 mg/kg. The liver glycogen and protein levels were both significantly (p<0.05) increased in diabetic mice at 250 and 500 mg/kg doses. Dianex increased the glucose tolerance significantly (p<0.05) in both normal and diabetic mice at all the doses tested. Histopathological examination showed that the formulation decreased streptozotocin induced injury to the tissues at all the doses tested. It produced significant (p<0.05) free radical scavenging activity against ABTS+, DPPH and hydroxyl free radicals at the concentrations ranging between 10-1000 microg/ml.Thus, in the present study, Dianex produced significant hypoglycemic activity in both normal and diabetic animals. It also reversed other diabetic complications in diabetic mice at 250 and 500 mg/kg doses. In our earlier study, Dianex was well tolerated in laboratory animals at higher doses (upto 10 g/kg in mice, acute toxicity; up to 2.5 g/kg in rats, subacute toxicity studies for 30 days) without exhibiting any toxic manifestation. Hence, Dianex may be useful in the treatment of diabetes mellitus.

  Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines.:Anticancer Res. 2005 Sep-Oct;25(5):3293-302.Ramachandran C, Rodriguez S, Ramachandran R, Raveendran Nair PK, Fonseca H, Khatib Z, Escalon E, Melnick SJ.Research Institute, Miami Children's Hospital, Miami, FL 33155, USA. cheppail.ramachandran@mch.com

 Curcumin (diferuloyl methane), the yellow-colored dietary pigment from the rhizomes of turmeric, has been recognized as a chemopreventive agent because of its antitumor, antioxidant and antiproliferative effects. The cytotoxic, apoptotic and gene regulatory effects of both turmeric and curcumin were investigated in the MCF-7 human breast cancer carcinoma cell line and compared with the effects in MCF-10A human mammary epithelial cells. MCF-7 cells were more sensitive to turmeric and curcumin than MCF-10A cells. MCF-10A cells retained comparatively less curcumin in the medium than MCF- 7 cells after 24 h, thereby reducing the cytotoxic effect. Curcumin induced a significantly higher percentage of apoptosis in MCF-7 than MCF-10A cells at all doses. Microarray hybridization of Clonetech apoptotic arrays with labeled first-strand probes of total RNA was performed to identify and characterize the genes regulated by curcumin in tumor cells. Of the 214 apoptosis-associated genes in the array, the expression of 104 genes was altered by curcumin treatment. The gene expression was altered up to 14-fold levels in MCF-7 as compared to only up to 1.5-fold in the MCF-10A cell line by curcumin. Curcumin up-regulated (>3 fold) 22 genes and down-regulated (<3-fold) 17 genes at both 25 microg/ml and 50 microg/ml doses in the MCF-7 cell line. The up-regulated genes include HIAP1, CRAF1, TRAF6, CASP1, CASP2, CASP3, CASP4, HPRT, GADD45, MCL-1, NIP1, BCL2L2, TRAP3, GSTP1, DAXX, PIG11, UBC, PIG3, PCNA, CDC10, JNK1 and RBP2. The down-regulated genes were TRAIL, TNFR, AP13, IGFBP3, SARP3, PKB, IGFBP, CASP7, CASP9, TNFSF6, TRICK2A, CAS, TRAIL-R2, RATS1, hTRIP, TNFb and TNFRSF5. While a dose-dependent gene expression change was noticed in some genes, opposite regulatory effects were induced by different curcumin doses in three apoptotic genes. These results suggest that curcumin induces apoptosis in breast cancer cells by regulation of multiple signaling pathways, indicating its potential use for prevention and treatment of cancer.

  Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on N-methyl-D: -aspartate-induced intracellular Ca(2+) increase.:Exp Brain Res. 2005 Dec;167(4):641-8. Epub 2005 Aug 3.Matteucci A, Frank C, Domenici MR, Balduzzi M, Paradisi S, Carnovale-Scalzo G, Scorcia G, Malchiodi-Albedi F.Department of Cell Biology and Neuroscience, Istituto Superiore di Sanit¨¤, Viale Regina Elena 299, 00161 Roma, Italy.

 Curcumin, an extract from the plant Curcuma longa with well-known antioxidant and anti-inflammatory activities, was tested as protective agent against excitotoxicity in rat retinal cultures. A 24 h-treatment with curcumin reduced N-methyl-D: -aspartate (NMDA)-mediated excitotoxic cell damage, estimated as decrease of cell viability and increase in apoptosis. The protection was associated with decrease of NMDA receptor-mediated Ca(2+) rise and reduction in the level of phosphorylated NR1 subunit of the NMDA receptor. These results enlighten a new pharmacological action of the plant extract, possibly mediated by a modulation of NMDA receptor activity.


  Effects of Guanyu capsule on the behavior and cerebral cortex monoamine neurotransmitters in depressive model of olfactory bulb damage rats.:Zhongguo Zhong Yao Za Zhi. 2005 May;30(10):782-5. Chinese.Wang JX, Zhang JJ, Zhong GS, Zhang DQ, Hu SM, Li W, Ou LN, Gao XM.Beijing University of Traditional Chinese Medicine, Beijing 100029, China.

 OBJECTIVE: To investigate the behavioral changes and the levels of monoamine neurotransmitters in the anterior cortex in the olfactory bulb damage rats after being treated with Guanyu capsules (GYC). METHOD: Open-field test and step-down passive avoidance test were used to observe the behavior in model rats. HPLC-ECD was used to analyze the influences of GYC on the levels of monoamine neurotransmitters. RESULT: In the model rats, there was a characteristic hyperactivity in the Open-field and learning deficits in step-down passive avoidance (P < 0.01). The contents of 5-HT reduced, and the rate of DOPAC/DA increased significantly (P < 0.01). GYC 1.2, 0.6 g x kg(-1) could correct behavioral changes increase the contents of 5-HT, and decrease DOPAC/DA level (P < 0.01). CONCLUSION: GYC can correct behavioral changes in rats model of olfactory bulb damage, and regulating 5-HT and DA metabolism in cortex is one of the antidepressive mechanisms of GYC.

  Effect of curcuma herbs on vasomotion and hemorheology in spontaneously hypertensive rat.:Am J Chin Med. 2005;33(3):449-57.

 Curcuma herbs have a vasodilator effect. The effects of C. longa, which induces only endothelium-independent vasodilatation, and C. zedoaria, which induces both endothelium-dependent and -independent vasodilatation, were studied on vasomotion and hemorheology in spontaneously hypertensive rats. Spontaneously hypertensive eight-week-old male rats were assigned to five groups. For 12 weeks, the control group received standard chow. The 3%CL (C. longa) group received standard chow containing 3% (wt/wt) C. longa. The 1%CZ and 3%CZ (C. zedoaria) groups received standard chow containing 1% and 3% (wt/wt) C. zedoaria, respectively. The captoril group received standard chow and 100 mg/kg/day of captoril in drinking water. Blood pressure, vasomotion, hemorheology, etc. were examined. Systolic blood pressure of the 3%CZ and captoril groups decreased significantly as compared to the control group. Acetylcholine-induced endothelium-dependent relaxations of the 3%CZ and captoril groups were increased to a greater degree, significantly, than the control group. When testing xanthine oxidase-induced contraction, the 3%CZ group was significantly decreased as compared to the control group. Low shear stress of whole blood viscosity showed the 3%CL and 3%CZ groups to be decreased significantly compared to the control group. Thus, Curcuma herbs have hypotensive and protective effect on the endothelium in spontaneously hypertensive rats. Especially, C. zedoaria is more effective than C. longa, and its mechanism is thought to be related to a radical scavenging effect and improvement of hemorheology.

  Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia.:Ann N Y Acad Sci. 2005 Jun;1043:440-51. Review.

 Hyperglycemia causes the autoxidation of glucose, glycation of proteins, and the activation of polyol metabolism. These changes accelerate generation of reactive oxygen species (ROS) and increases in oxidative chemical modification of lipids, DNA, and proteins in various tissues. Oxidative stress may play an important role in the development of complications in diabetes such as lens cataracts, nephropathy, and neuropathy. Glycation reactions, especially Maillard reactions, occur in vivo as well as in vitro and are associated with the chronic complications of diabetes mellitus and aging and age-related diseases by increases in oxidative chemical modification of lipids, DNA, and proteins. In particular, long-lived proteins such as lens crystallines, collagens, and hemoglobin may react with reducing sugars to form advanced glycation end products (AGEs). Recently, we found a novel type of AGE, named MRX, and we found that MRX is a good biomarker for detecting oxidative stress produced during Maillard reaction. We also examined in detail the role of lipid peroxidation reaction in hyperglycemia and found that hexanoyl modification formed by the reaction of oxidized lipids and proteins must be important for oxidative stress. Detailed analyses of the formation mechanism of hexanoyl lysine (HEL) moiety in proteins were conducted, and excretion of HEL into urine was quantified by using LC/MS/MS. Macrophages and neutrophils play an important role in oxidative stress during hyperglycemia, and we determined that oxidatively modified tyrosines are a good biomarker for formation of oxidative stress at an early stage. Immunochemical analyses by application of monoclonal antibodies specific to lipid hydroperoxide-modified proteins produced by polyunsaturated fatty acids including docosahexaenoic acid (DHA) in oxidative stress caused by hyperglycemia were conducted, and the relationship between glycation and lipid peroxidation reactions both by chemical and immunochemical approaches are discussed. Recently, we put much more focus on dietary antioxidants for prevention of diabetic complications. Curcuminoids, the main yellow pigments in Curcuma longa (turmeric), have been used widely and for a long time in the treatment of sprain and inflammation in indigenous medicine. Curcumin is the main component of turmeric, and two minor components are also present as the curcuminoids. Curcuminoids possess antioxidant activity. Protective effects of curcumin (U1) and one of its major metabolites, tetrahydrocurcumin (THU1), have been examined for development of diabetic cataract in 25% galactose-fed SD rats. Through detailed examination of protective mechanisms of THU1, it was found that THU1 showed that scavenger ROS not only formed during hyperglycemia, but also induced antioxidative enzymes including detoxification enzymes such as glutathine S-transferase. THU1 also showed significant increase of glutathione concentration in the cultured rat lens. Glutathione (gamma-glutamylcysteinyl glycine [GSH]) is thought to be an important factor in cellular function and defense against oxidative stress, and we found that dietary GSH suppresses oxidative stress in vivo in prevention of diabetic complications such as diabetic nephropathy and neuropathy.

  A HPLC method for the analysis of germacrone in rabbit plasma and its application to a pharmacokinetic study of germacrone after administration of zedoary turmeric oil.:J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Sep 5;823(2):172-6.You J, Cui FD, Li QP, Yong-sheng W, Han X, Yu YW.Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, China. youjiandoc@yahoo.com.cn

 A validated new, simple and highly sensitive reversed-phase HPLC method is developed for studying the pharmacokinetics of germacrone after intravenous administration of zedoary turmeric oil (ZTO) oil-in-water microemulsion. The method did not require a complex and expensive equipment. A high extraction recovery (>80%) of germacrone was obtained. Linear calibration curves obtained with the peak-area ratio (y) of germacrone to internal standard (tanshinoneIIA) versus drug concentration (x) were found to be linear between 8.08 and 808 ng/ml. The limit of quantitation was 8.08 ng/ml.The monitored compounds were completely separated from others in ZTO and from endogenous species in plasma by HPLC. Pharmacokinetic investigations were performed on 18 male rabbits after intravenous administration of ZTO microemulsion via the ear vein at germacrone doses of 3.2, 6.4 and 9.6 mg/kg. The plasma concentration-time data fit to a two-compartment intravenous model with a weight of 1/C(2) (C: germacrone concentration in plasma). Germacrone exhibited linear pharmacokinetics after intravenous administration of ZTO microemulsion to rabbits over the germacrone dose range 3.2-9.6 mg/ml.

  Alcoholic turmeric extract simultaneously activating murine lymphocytes and inducing apoptosis of Ehlrich ascitic carcinoma cells.:Int Immunopharmacol. 2005 Sep;5(10):1574-81. Epub 2005 Apr 14.Chakravarty AK, Yasmin H.Immunology & Cell Biology Laboratory, Centre for Life Sciences, North Bengal University, Siliguri - 734430, West Bengal, India. prof_ashim_chakravarty@rediffmail.com

 In the present investigation ethanolic turmeric extract has been found to play diabolically opposite role on murine lymphocytes and on Ehlrich ascitic carcinoma cells. Turmeric stimulates the lymphocytes into the effector pathway as studied through in vitro viability, blastogenesis and (3)H-TdR incorporation and also seems to be healthy under scanning electron microscopy (SEM). SEM revealed the formation of cytoplasmic blebs and plasma membrane disintegration of tumor cells with ethanolic turmeric extract treatment, suggesting turmeric to be initiating apoptosis of tumor cells. Thus, in the present work viability of the cells, blastogenesis, DNA synthesis and SEM study establish the fact that turmeric is a conducive agent for lymphocytes and inhibitory as well as apoptotic for tumor cells.


  Modulatory effect of fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases in streptozotocin induced diabetic rats.:Plant Foods Hum Nutr. 2005 Jun;60(2):87-91.Kumar GS, Shetty AK, Salimath PV.Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore-570 020, India. paramahans1954@yahoo.com

 To elucidate the effect of feeding fenugreek seed mucilage and spent turmeric (10%) on disaccharidases activities, the specific activities of intestinal and renal disaccharidases viz., sucrase, maltase and lactase were measured in streptozotocin induced diabetic rats. Specific activities of intestinal disaccharidases were increased significantly during diabetes and amelioration of these activities during diabetes was clearly visible by supplementing fenugreek seed mucilage and spent turmeric in the diet. However during diabetes renal disaccharidases activities were significantly lower than those in the control rats. Fenugreek seed mucilage and spent turmeric supplementations were beneficial in alleviating the reduction in maltase activity during diabetes, however not much change in the activities of sucrase and lactase was observed upon feeding. This positive influence of feeding fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases clearly indicates their beneficial role in the management of diabetes.

  Curcuminoids purified from turmeric powder modulate the function of human multidrug resistance protein 1 (ABCC1).:Cancer Chemother Pharmacol. 2006 Feb;57(3):376-88. Epub 2005 Jul 14.Chearwae W, Wu CP, Chu HY, Lee TR, Ambudkar SV, Limtrakul P.Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Thailand.

 Multidrug resistance is a major cause of chemotherapy failure in cancer patients. One of the resistance mechanisms is the overexpression of drug efflux pumps such as P-glycoprotein and multidrug resistance protein 1 (MRP1, (ABCC1)). In this study, curcumin mixture and three major curcuminoids purified from turmeric (curcumin I, II, and III) were tested for their ability to modulate the function of MRP1 using HEK293 cells stably transfected with MRP1-pcDNA3.1 and pcDNA3.1 vector alone. The IC(50) of curcuminoids in these cell lines ranged from 14.5-39.3 microM. Upon treating the cells with etoposide in the presence of 10 microM curcuminoids, the sensitivity of etoposide was increased by several folds only in MRP1 expressing and not in pcDNA3.1-HEK 293 cells. Western blot analysis showed that the total cellular level of MRP1 protein level was not affected by treatment with 10 microM curcuminoids for three days. The modulatory effect of curcuminoids on MRP1 function was confirmed by the inhibition of efflux of two fluorescent substrates, calcein-AM and fluo4-AM. Although all the three curcuminoids increased the accumulation of fluorescent substrates in a concentration-dependent manner, curcumin I was the most effective inhibitor. In addition, curcuminoids did not affect 8-azido[alpha-(32)P]ATP binding, however they did stimulate the basal ATPase activity and inhibited the quercetin-stimulated ATP hydrolysis of MRP1 indicating that these bioflavonoids interact most likely at the substrate-binding site(s). In summary, these results demonstrate that curcuminoids effectively inhibit MRP1-mediated transport and among curcuminoids, curcumin I, a major constituent of curcumin mixture, is the best modulator.

  Research on the technology of soaking under pressure and cutting process of Radix Curcumae.:Zhongguo Zhong Yao Za Zhi. 2005 Apr;30(7):498-500. Chinese.Huang WH, Guo BL, Xue J, Yu JG, Zou ZM, Sun L.Institute of Medicinal plant Development, Chinese Academy of Medica Sciences and Chinese Peking Union Medica College, Beijing 100094, China.

 OBJECTIVE: To determine the best processing technology parameters. METHOD: The changes of the weights, volatile constituents, total extract quantities by MeOH or CHCl3 and curcumenol contents of the roots of Curcuma wenyujin and C. kwangsiensis roots before and after water soaking were determined, so as to determine the quality control index for the process of preparing Yujin slices. The shortest soaking and moistening time and the appropriate drying temperature were studied. RESULT AND CONCLUSION: (1) The weight was decreased and the quantities of volatile constituents were changed during water soaking process. But the total extracts quantities and the curcumenol contents didn't change obviously. So the quality control index was decided as soaking as short as possible. (2) The soaking time could be decreased by using high pressure. The soaking time was related with the short diameter of the cross section of the root. (3) The soaking under pressure technology is that soaking on -0.095 MPa for 0.5 h, then on 0.14 MPa for 10-16 h, and moistening for 36-48 h, cutting drying in room temperature or less than 40 degrees C.

  In vitro enzyme inhibition activities of crude ethanolic extracts derived from medicinal plants of Pakistan.:Nat Prod Res. 2005 Sep;19(6):567-71.Khattak S, Saeed-Ur-Rehman , Shah HU, Khan T, Ahmad M.Department of Chemistry, University of Peshawar, Peshawar - 25120, Pakistan. somiakhattak@yahoo.com

 Twenty two crude ethanolic extracts from 14 indigenous medicinal plants were subjected to enzyme inhibition screening against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase enzymes (LO). Three extracts showed activity against AChE, nine extracts were found to be active against BChE and four extracts inhibited the enzyme LO. The most significant inhibition activities (> or =50%) were found in extracts derived from Aloe vera (leaves), Alpinia galanga (rhizome), Curcuma longa (rhizome), Cymbopogon citratus (leaves), Ocimum americanum (leaves), Ocimum americanum (stem) and Withania somnifera (roots).

  Chemopreventive effects of embelin and curcumin against N-nitrosodiethylamine/phenobarbital-induced hepatocarcinogenesis in Wistar rats.:Fitoterapia. 2005 Sep;76(6):549-55. Sreepriya M, Bali G.Department of Microbiology and Biotechnology, Jnana Bharti Campus, Bangalore University, Bangalore 560 056, Karnataka, India. mpriya7@yahoo.com

 The effects of embelin (50 mg/kg/day), a benzoquinone derivative of Embelia ribes, and the effects of curcumin (100 mg/kg/day), the active principle of Curcuma longa, against N-nitrosodiethylamine (DENA)-initiated and phenobarbital (PB)-promoted hepatocarcinogenesis were studied in Wistar rats. They were able to prevent the induction of hepatic hyper plastic nodules, body weight loss, increase in the levels of hepatic diagnostic markers, and hypoproteinemia induced by DENA/PB treatment. Hence, results of our study suggest the possible chemopreventive effects of embelin (EMB) and curcumin (CUR) against DENA/PB-induced hepatocarcinogenesis in Wistar rats.


  The effect of turmeric extracts on inflammatory mediator production.:Phytomedicine. 2005 Jun;12(6-7):445-52.Lantz RC, Chen GJ, Solyom AM, Jolad SD, Timmermann BN.Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA. lantz@email.arizona.edu

 Major compounds of several commonly used botanicals, including turmeric, have been purported to have anti-inflammatory actions. In order to test the anti-inflammatory activity of compounds isolated from rhizomes of Curcuma longa L. (Zingiberaceae), we have established an in vitro test system. HL-60 cells were differentiated and exposed to lipopolysaccharide (LPS) from Escherichia coli (1 microg/ml) in the presence or absence of botanical compounds for 24 h. Supernatants were collected and analyzed for the production of tumor necrosis factor alpha (TNF-alpha) and prostaglandin E2 (PGE2) using standard ELISA assays. Water-soluble extracts were not cytotoxic and did not exhibit biological activity. Organic extracts of turmeric were cytotoxic only at concentrations above 50 microg/ml. Crude organic extracts of turmeric were capable of inhibiting LPS-induced TNF-alpha (IC50 value = 15.2 microg/ml) and PGE2 (IC50 value = 0.92 microg/ml) production. Purified curcumin was more active than either demethoxy- or bisdemethoxycurcumin. Fractions and subfractions of turmeric extracts collected via preparative HPLC had differing biological activity, ranging from no activity to IC50 values of < 1 microg/ml. For some fractions, subfractionation resulted in a loss of activity, indicating interaction of the compounds within the fraction to produce an anti-inflammatory effect. A combination of several of the fractions that contain the turmeric oils was more effective than the curcuminoids at inhibiting PGE2. While curcumin inhibited COX-2 expression, turmeric oils had no effect on levels of COX-2 mRNA.

  The effects of curcumin on depressive-like behaviors in mice.:Eur J Pharmacol. 2005 Jul 25;518(1):40-6.Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ.Department of Pharmacology, School of Basic Medical Science, Peking University, 38 Xueyuan Road, Beijing, 100083, PR China.

 Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicinal formula, which has been used effectively to treat depression-related diseases in China. There is no information available about the antidepressant activity of curcumin, the active component of curcuma longa. In the present study, we analyzed the effects of curcumin on depressive-like behaviors in mice, using two animal models of depression. Our results showed that curcumin treatment at 5 and 10 mg/kg (p.o.) significantly reduced the duration of immobility in both the tail suspension and forced swimming tests. These doses that affected the immobile response did not affect locomotor activity. In addition, the neurochemical assays showed that curcumin produced a marked increase of serotonin and noradrenaline levels at 10 mg/kg in both the frontal cortex and hippocampus. Dopamine levels were also increased in the frontal cortex and the striatum. Moreover, curcumin was found to inhibit monoamine oxidase activity in the mouse brain. These findings suggest that the antidepressant-like effects of curcumin may involve the central monoaminergic neurotransmitter systems.

  A potential role of the curry spice curcumin in Alzheimer's disease.:Curr Alzheimer Res. 2005 Apr;2(2):131-6. Review.Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL.University of California, Los Angeles, Department of Neurology, Alzheimer's Disease Research Center, Los Angeles, CA 90095, USA. jringman@mednet.ucla.edu

 There is substantial in-vitro data indicating that curcumin has antioxidant, anti-inflammatory, and anti-amyloid activity. In addition, studies in animal models of Alzheimer's disease (AD) indicate a direct effect of curcumin in decreasing the amyloid pathology of AD. As the widespread use of curcumin as a food additive and relatively small short-term studies in humans suggest safety, curcumin is a promising agent in the treatment and/or prevention of AD. Nonetheless, important information regarding curcumin bioavailability, safety and tolerability, particularly in an elderly population is lacking. We are therefore performing a study of curcumin in patients with AD to gather this information in addition to data on the effect of curcumin on biomarkers of AD pathology.

  Curcumin inhibits ROS formation and apoptosis in methylglyoxal-treated human hepatoma G2 cells.:Ann N Y Acad Sci. 2005 May;1042:372-8. Chan WH, Wu HJ, Hsuuw YD.Department of Bioscience Technology, Chung Yuan Christian University, Chung Li, Taiwan 32023. whchan@cycu.edu.tw

 Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Elevated MG levels in diabetes patients are believed to contribute to diabetic complications. MG is cytotoxic through induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties. In the present study, we investigated the effect of curcumin on MG-induced apoptotic events in human hepatoma G2 cells. We report that curcumin prevented MG-induced cell death and apoptotic biochemical changes such as mitochondrial release of cytochrome c, caspase-3 activation, and cleavage of PARP (poly [ADP-ribose] polymerase). Using the cell permeable dye 2',7'-dichlorofluorescein diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we found that curcumin abolished MG-stimulated intracellular oxidative stress. The results demonstrate that curcumin significantly attenuates MG-induced ROS formation, and suggest that ROS triggers cytochrome c release, caspase activation, and subsequent apoptotic biochemical changes.

  Antiatherosclerotic effects of dietary supplementations of garlic and turmeric: Restoration of endothelial function in rats.:Life Sci. 2005 Jul 8;77(8):837-57. Epub 2005 Apr 14.Zahid Ashraf M, Hussain ME, Fahim M.Department of Physiology, V. P. Chest Institute, University of Delhi, Delhi-110 007, India.

 Protections of endothelial integrity by elimination of certain risk have proven to be effective in maintaining hemostasis and in slowing the progress of the cardiovascular disease. Indigenous drugs are the natural source of protection against these disorders, which can be used more effectively by the knowledge of their active ingredients as well as by their mechanism of action. Most prominent among these drugs are garlic, [Alium sativum L., Family: Liliaceae, Bulbs] and turmeric [Curcuma longa L., Family: Zingiberaceae, Rhizomes]; commonly used Indian traditional spices. In the present study, we examined the atheroscleroprotective potential of diet supplementation of garlic and turmeric by measuring serum lipid profile, changes in cardiovascular parameters i.e. arterial blood pressure, electrocardiogram and heart rate. We further tried to elucidate the mechanism of restoration of endothelial function and the role of endothelium-derived factors mainly, nitric oxide (NO) and cycloxygenase derived contracting factors. A notable restoration of arterial blood pressure was seen in animals on garlic and turmeric supplemented diet. Animals on supplemented diet showed a significantly enhanced vasorelaxant response to adenosine, acetylcholine, isoproterenol and contractile effect of 5-hyderoxytryptamine was significantly attenuated. Inhibition of these responses by L-NMMA was smaller in tissues from herbal treated animals. Incubation of tissues with L-arginine (10(-5) M) resulted in a significant reversal of L-NMMA induced inhibition of endothelium-mediated relaxation, which appeared to be pronounced in rings from animals supplemented with herbs as compared to hypercholesterolemic animals. Addition of indomethacin (10(-5) M) augmented the relaxation in all the groups of animals. The present study demonstrated that garlic and turmeric are potent vasorelaxants as well as reduce the atherogenic properties of cholesterol. Whether combination of these vasodilators in cardiovascular disorders with increased peripheral vascular resistance remains to be determined.


  Identification and quantitation of eleven sesquiterpenes in three species of Curcuma rhizomes by pressurized liquid extraction and gas chromatography-mass spectrometry.:J Pharm Biomed Anal. 2005 Sep 15;39(3-4):552-8.Yang FQ, Li SP, Chen Y, Lao SC, Wang YT, Dong TT, Tsim KW.Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.

 In this paper, GC-MS and pressurized liquid extraction (PLE) was developed for identification and quantitative determination/estimation 11 sesquiterpenes including germacrene D, curzerene, gamma-elemene, furanodienone, curcumol, isocurcumenol, furanodiene, germacrone, curdione, curcumenol and neocurdione in Ezhu which are derived from three species of Curcuma, i.e., Curcuma phaeocaulis, Curcuma wenyujin and Curcuma kwangsiensis by using an analogue as standard. The results showed the methodology could quantitatively compare the quality of three species of Curcuma. The contents of investigated sesquiterpenes in three species of Curcuma were high variant. Hierarchical clustering analysis based on characteristics of 11 identified peaks in GC profiles showed that 18 samples were divided into two main clusters, C. phaeocaulis and C. wenyujin, respectively. C. kwangsiensis showed the characters closed to C. phaeocaulis or C. wenyujin based on its location. Five components such as furanodienone, germacrone, curdione, curcumenol and neocurdione were optimized as markers for quality control of Ezhu.

  Protective role of tetrahydrocurcumin (THC) an active principle of turmeric on chloroquine induced hepatotoxicity in rats.:J Pharm Pharm Sci. 2005 Apr 30;8(1):115-23.Pari L, Amali DR.Department of Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, India. paribala@sancharnet.in

 PURPOSE: Tetrahydrocurcumin (THC) is an antioxidative substance, which is derived from curcumin, the component of turmeric. In the present investigation, the effect of THC and curcumin against chloroquine (CQ) induced hepatotoxicity were studied in female Wistar rats. METHODS: On single oral administration of CQ (970 mg/kg body weight) the activities of serum marker enzymes namely aspartate transaminase, alanine transaminase and alkaline phosphatase and the levels of bilirubin were significantly increased with significant alterations of lipids in serum and lipidperoxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides in plasma and liver were also elevated in CQ treated rats. The levels of non-enzymic antioxidants (vitamin C, vitamin E and reduced glutathione) and enzymic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) were also decreased in CQ treated rats. Administration of THC (80 mg/kg body weight) and curcumin (80 mg/kg body weight) for 8 days before and 7 days after single administration of CQ significantly decreased the activities of serum markers and lipids in serum. In addition, the level of TBARS and hydroperoxides were significantly decreased with significant increase in non-enzymic and enzymic antioxidants on treatment with THC and curcumin. The biochemical observation was supplemented by histopathological examination of liver section. The results of the study reveal that THC shows more pronounced protective effect than curcumin against CQ induced toxicity.

  The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced NF-kappaB signaling, release of pro-inflammatory cytokines/chemokines and attenuates adhesion in late infection.:Biol Chem. 2005 May;386(5):481-90.Wessler S, Muenzner P, Meyer TF, Naumann M.Paul-Ehrlich-Institute, D-63225 Langen, Germany.

 Neisseria gonorrhoeae (Ngo) is a Gram-negative pathogenic bacterium responsible for an array of diseases ranging from urethritis to disseminated gonococcal infections. Early events in the establishment of infection involve interactions between Ngo and the mucosal epithelium, which induce a local inflammatory response. Here we analyzed the molecular mechanism involved in the Ngo-induced induction of the proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), and IL-8. We identified the immediate early response transcription factor nuclear factor kappaB (NF-kappaB) as a key molecule for the induction of cytokine release. Ngo-induced activation of direct upstream signaling molecules was demonstrated for IkappaB kinase alpha and beta (IKKalpha and IKKbeta) by phosphorylation of IkappaBalpha as a substrate and IKK autophosphorylation. Using dominant negative cDNAs encoding kinase-dead IKKalpha, IKKbeta, and NF-kappaB-inducing kinase (NIK), Ngo-induced NF-kappaB activity was significantly inhibited. Curcumin, the yellow pigment derived from Curcuma longa, inhibited IKKalpha, IKKbeta and NIK, indicating its strong potential to block NF-kappaB-mediated cytokine release and the innate immune response. In addition to the inhibition of Ngo-induced signaling, curcumin treatment of cells completely abolished the adherence of bacteria to cells in late infection, underlining the high potential of curcumin as an anti-microbial compound without cytotoxic side effects.

  Curcumin and turmeric delay streptozotocin-induced diabetic cataract in rats.:Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2092-9.Suryanarayana P, Saraswat M, Mrudula T, Krishna TP, Krishnaswamy K, Reddy GB.National Institute of Nutrition (ICMR), Hyderabad, India.

 PURPOSE: The purpose of this study was to investigate the effect of curcumin and its source, turmeric, on streptozotocin-induced diabetic cataract in rats. METHODS: Wistar-NIN rats were selected and diabetes was induced by streptozotocin (35 mg/kg body weight, intraperitoneally) and divided into four groups (group II-V). The control (group I) rats received only vehicle. Group I and II animals received an unsupplemented AIN-93 diet, and those in groups III, IV, and V received 0.002% and 0.01% curcumin and 0.5% turmeric, respectively, in an AIN-93 diet for a period of 8 weeks. Cataract progression due to hyperglycemia was monitored by slit lamp biomicroscope and classified into four stages. At the end of 8 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract such as oxidative stress, polyol pathway, alterations in protein content and crystallin profile in the lens were investigated, to understand the possible mechanism of action of curcumin and turmeric. Blood glucose and insulin levels were also determined. RESULTS: Although, both curcumin and turmeric did not prevent streptozotocin-induced hyperglycemia, as assessed by blood glucose and insulin levels, slit lamp microscope observations indicated that these supplements delayed the progression and maturation of cataract. The present studies suggest that curcumin and turmeric treatment appear to have countered the hyperglycemia-induced oxidative stress, because there was a reversal of changes with respect to lipid peroxidation, reduced glutathione, protein carbonyl content and activities of antioxidant enzymes in a significant manner. Also, treatment with turmeric or curcumin appears to have minimized osmotic stress, as assessed by polyol pathway enzymes. Most important, aggregation and insolubilization of lens proteins due to hyperglycemia was prevented by turmeric and curcumin. Turmeric was more effective than its corresponding levels of curcumin. CONCLUSIONS: The results indicate that turmeric and curcumin are effective against the development of diabetic cataract in rats. Further, these results imply that ingredients in the study's dietary sources, such as turmeric, may be explored for anticataractogenic agents that prevent or delay the development of cataract.

  Application of capillary zone electrophoresis in the separation and determination of the curcuminoids in urine.:J Pharm Biomed Anal. 2005 Jun 1;38(1):133-8. Epub 2005 Jan 12.Yuan K, Weng Q, Zhang H, Xiong J, Xu G.National Chromatographic R.&A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116011, PR China.

 The major components of the plant curcuma longa are the curcuminoids that include curcumin, demethoxycurcumin and bisdemethoxycurcumin. It has been reported the curcuminoids have some important activities. A new CZE method with diode array detection has been developed for the separation and determination of the curcumin, demethoxycurcumin and bisdemethoxycurcumin. Three curcuminoids could be readily separated within 7 min with a 15 mM sodium tetraborate buffer containing 10% methanol (v/v) at pH 10.8, 25 kV and 30 degrees C. The method has been validated and shows good performance with respect to selectivity, reproducibility, linearity, limits of detection and recovery. The proposed method was successfully applied to determine the curcuminoids in urine.


  Chemopreventive and therapeutic effects of curcumin.:Cancer Lett. 2005 Jun 8;223(2):181-90. Epub 2004 Nov 11. Review.Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, Dicato M, Diederich M.Laboratoire de Biologie Mol¨¦culaire et Cellulaire du Cancer, H?pital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.

 Chemoprevention is a promising anti-cancer approach with reduced secondary effects in comparison to classical chemotherapy. Curcumin, one of the most studied chemopreventive agents, is a natural compound extracted from Curcuma longa L. that allows suppression, retardation or inversion of carcinogenesis. Curcumin is also described as an anti-tumoral, anti-oxidant and anti-inflammatory agent capable of inducing apoptosis in numerous cellular systems. In this review, we describe both properties and mode of action of curcumin on carcinogenesis, gene expression mechanisms and drug metabolism.

  Curcumin prevents methylglyoxal-induced oxidative stress and apoptosis in mouse embryonic stem cells and blastocysts.:J Cell Physiol. 2005 Dec;205(3):379-86.Hsuuw YD, Chang CK, Chan WH, Yu JS.Department of Animal Science, National Pingtung University of Science and Technology, Taiwan, Republic of China.

 Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Elevated MG levels in diabetes patients are believed to contribute to diabetic complications. MG is cytotoxic through induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties. In the present study, we examined the effect of curcumin on apoptotic biochemical events caused by incubation of ESC-B5 cells with MG. Curcumin inhibited the MG-induced DNA fragmentation, caspase-3 activation, cleavage of PARP, mitochondrial cytochrome c release, and JNK activation. Importantly, curcumin also inhibited the MG-stimulated increase of reactive oxygen species (ROS) in these cells. In addition, we demonstrated that curcumin prevented the MG-induced apoptosis of mouse blastocysts isolated from pregnant mice. Moreover, curcumin significantly reduced the MG-mediated impairment of blastocyst development from mouse morulas. The results support the hypothesis that curcumin inhibits MG-induced apoptosis in mouse ESC-B5 cells and blastocysts by blocking ROS formation and subsequent apoptotic biochemical events.

  Protective effect of curcumin during selenium induced toxicity on dehydrogenases in hepatic tissue.:Indian J Physiol Pharmacol. 2005 Jan;49(1):111-4. Padmaja S, Raju TN.Physiology Division, Department of Zoology, University College of Science, Osmania University, Hyderabad - 500 007.

 Selenium administration resulted in a marked decrease in the activity levels of the liver succinate dehydrogenase, malate dehydrogenase, and lactate dehydrogenase while pyruvate dehydrogenase increased significantly (P<0.001) in the wistar rat. The degree of decrease of these enzymes was significantly less (P<0.001) when rats were treated with curcumin, a natural constituent Curcuma longa. Curcumin seems to prevent oxidative damage mediated through selenium and protect the dehydrogenases possibly through its anti-oxidative property.

  Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity.:J Biol Chem. 2005 Jul 1;280(26):25284-90. Epub 2005 May 6.Fang J, Lu J, Holmgren A.Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-17177 Stockholm, Sweden.

 The thioredoxin reductase (TrxR) isoenzymes, TrxR1 in cytosol or nucleus and TrxR2 in mitochondria, are essential mammalian selenocysteine (Sec)-containing flavoenzymes with a -Gly-Cys-Sec-Gly active site. TrxRs are the only enzymes catalyzing the NADPH-dependent reduction of the active site disulfide in thioredoxins (Trxs), which play essential roles in substrate reductions, defense against oxidative stress, and redox regulation by thiol redox control. TrxRs have been found to be overexpressed by a number of human tumors. Curcumin, which is consumed daily by millions of people, is a polyphenol derived from the plant Curcuma longa. This phytochemical has well known anticancer and antiangiogenic properties. In this study we report that rat TrxR1 activity in Trx-dependent disulfide reduction was inhibited by curcumin. The IC(50) value for the enzyme was 3.6 microM after incubation at room temperature for 2 h in vitro. The inhibition occurred with enzyme only in the presence of NADPH and persisted after removal of curcumin. By using mass spectrometry and blotting analysis, we proved that this irreversible inhibition by curcumin was caused by alkylation of both residues in the catalytically active site (Cys(496)/Sec(497)) of the enzyme. However, the curcumin-modified enzyme showed a strongly induced NADPH oxidase activity to produce reactive oxygen species. Inhibition of TrxR by curcumin added to cultured HeLa cells was also observed with an IC(50) of around 15 microM. Modification of TrxR by curcumin provides a possible mechanistic explanation for its cancer preventive activity, shifting the enzyme from an antioxidant to a prooxidant.

  Plant medicines of Indian origin for wound healing activity: a review.:Int J Low Extrem Wounds. 2003 Mar;2(1):25-39.Biswas TK, Mukherjee B.Department of Sharira Kriya, J. B. Roy State Ayurvedic Medical College and Hospital.

 Research on wound healing drugs is a developing area in modern biomedical sciences. Scientists who are trying to develop newer drugs from natural resources are looking toward the Ayurveda, the Indian traditional system of medicine. Several drugs of plant, mineral, and animal origin are described in the Ayurveda for their wound healing properties under the term Vranaropaka. Most of these drugs are derived from plant origin. Some of these plants have been screened scientifically for the evaluation of their wound healing activity in different pharmacological models and patients, but the potential of most remains unexplored. In a few cases, active chemical constituents were identified. Some Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon, Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa, Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica, Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental models. This paper presents a limited review of plants used in Ayurvedic medicine.


  Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically diabetic KK-Ay mice.:Biol Pharm Bull. 2005 May;28(5):937-9.

 The turmeric (Curcuma longa L. rhizomes) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-A(y) mice. In an in vitro evaluation, the extract stimulated human adipocyte differentiation in a dose-dependent manner and showed human peroxisome proliferator-activated receptor (PPAR)-gamma ligand-binding activity in a GAL4-PPAR-gamma chimera assay. The main constituents of the extract were identified as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.

  Pharmacological basis for the use of turmeric in gastrointestinal and respiratory disorders.:Life Sci. 2005 May 13;76(26):3089-105. Gilani AH, Shah AJ, Ghayur MN, Majeed K.Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi-74800, Sindh, Pakistan. anwar.gilani@aku.edu

 This study was carried out to provide scientific basis for the medicinal use of turmeric (Curcuma longa) in gastrointestinal and respiratory disorders. The crude extract of turmeric (Cl.Cr), relaxed the spontaneous and K+ (80 mM)-induced contractions in isolated rabbit jejunum as well as shifted the CaCl2 concentration-response curves. In rabbit tracheal preparation, Cl.Cr inhibited carbachol and K(+)-induced contractions. In anesthetized rats, Cl.Cr produced variable responses on blood pressure with a mixture of weak hypertensive and hypotensive actions. In rabbit aorta, Cl.Cr caused a weak vasoconstrictor and a vasodilator effect on K+ and phenylephrine-induced contractions. In guinea-pig atria, Cl.Cr inhibited spontaneous rate and force of contractions at 14-24 times higher concentrations. Activity directed fractionation revealed that the vasodilator and vasoconstrictor activities are widely distributed in the plant with no clear separation into the polar or non-polar fractions. When used for comparison, both curcumin and verapamil caused similar inhibitory effects in all smooth muscle preparations with relatively more effect against K(+)-induced contractions and that both were devoid of any vasoconstrictor effect and curcumin had no effect on atria. These data suggest that the inhibitory effects of Cl.Cr are mediated primarily through calcium channel blockade, though additional mechanism cannot be ruled out and this study forms the basis for the traditional use of turmeric in hyperactive states of the gut and airways. Furthermore, curcumin, the main active principle, does not share all effects of turmeric.

  Antimicrobial activity of Curcuma zedoaria and Curcuma malabarica tubers.:J Ethnopharmacol. 2005 May 13;99(1):147-51.Wilson B, Abraham G, Manju VS, Mathew M, Vimala B, Sundaresan S, Nambisan B.Division of Crop Utilization and Biotechnology, Central Tuber Crops Research Institute, Sreekariyam, Thiruvananthapuram, Kerala 695017, India.

 The antimicrobial activity of extracts of Curcuma zedoaria and Curcuma malabarica tubers was tested against six bacterial and two fungal strains using the agar well diffusion and broth dilution methods. Petroleum ether, hexane, chloroform, acetone and ethanol extracts exhibited antibacterial as well as antifungal activity. Acetone and hexane extracts of both tubers showed comparable antimicrobial activity as indicated by minimum inhibitory concentration (MIC) values, but other extracts of Curcuma malabarica showed significantly lower activity than those of Curcuma zedoaria. The MIC values for different strains and extracts ranged from 0.01 to 0.15 mg/ml in Curcuma zedoaria and from 0.01 to 0.94 mg/ml in Curcuma malabarica. Staphylococcus aureus (Gram positive) was inhibited by Curcuma malabarica but not by Curcuma zedoaria. This study is the first report of the antimicrobial properties of Curcuma malabarica. The findings also support the use of Curcuma zedoaria tubers in traditional medicine for the treatment of bacterial and fungal infections.

   Induction of apoptosis by curcumin and its implications for cancer therapy.:Curr Cancer Drug Targets. 2005 Mar;5(2):117-29. Review.Karunagaran D, Rashmi R, Kumar TR.Cancer Biology Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala 695 014, India. dkarunagaran@hotmail.com

 Curcumin (diferuloyl methane), the yellow pigment in turmeric (Curcuma longa), is a potent chemopreventive agent that inhibits proliferation of cancer cells by arresting them at various phases of the cell cycle depending upon the cell type. Curcumin-induced apoptosis mainly involves the mitochondria-mediated pathway in various cancer cells of different tissues of origin. In some cell types like thymocytes, curcumin induces apoptosis-like changes whereas in many other normal and primary cells curcumin is either inactive or inhibits proliferation, but does not appear to induce apoptosis. These together with reports that curcumin protects cells against apoptosis induced by other agents, underscore the need for further understanding of the multiple mechanisms of cell death unleashed by curcumin. Tumor cells often evade apoptosis by expressing several antiapoptotic proteins, down-regulation and mutation of proapoptotic genes and alterations in signaling pathways that give them survival advantage and thereby allow them to resist therapy-induced apoptosis. Many researchers including ourselves, have demonstrated the involvement of several pro and antiapoptotic molecules in curcumin-induced apoptosis, and ways to sensitize chemoresistant cancer cells to curcumin treatment. This review describes the mechanisms of curcumin-induced apoptosis currently known, and suggests several potential strategies that include down-regulation of antiapoptotic proteins by antisense oligonucleotides, use of proapoptotic peptides and combination therapy, and other novel approaches against chemoresistant tumors. Several factors including pharmacological safety, scope for improvement of structure and function of curcumin and its ability to attack multiple targets are in favor of curcumin being developed as a drug for prevention and therapy of various cancers.

  Study on preparation of beta-cyclodextrin inclusion volatile oil from Rhizoma Curcumae.:Zhong Yao Cai. 2004 Nov;27(11):866-9. Chinese.Li D, Xu J, Xia S, Pu C, Jin S, Liu M.Nanjing Institute for Drug Control, Nanjing.

 OBJECTIVE: To study optimum inclusion process conditions for volatile oil from Rhizoma Curcumae. METHOD: The study was carried out with orthogonal design. The process conditions were studied by determining the utilazision ratio of volatile oil from Rhizoma Curcumae, the oil-bearing rate and extract ratio of inclusion compound. RESULTS: The optimum preparation conditions for inclusion were established as: volatile oil:beta-CD was 1:8, the inclusion temperature was at 80 degrees C and inclusion time for 3 h, ultilizasion rate of volatile oil was 86%. CONCLUSION: The method can be used for mass production.


  The effect of curcumin on bladder cancer cell line EJ in vitro.:Zhong Yao Cai. 2004 Nov;27(11):848-50. Chinese.Sun M, Yang Y, Li H, Su B, Lu Y, Wei Q, Fan T.Department of Urology of Westchina Hospital of Sichuan University, Chengdu.

 OBJECTIVE: To observe the effect of curcumin on bladder cancer cell line EJ in vitro. METHODS: Cell morphology, MTT, flow cytometer, immunocytochemical method for detecting NF-KB, Cyclin D1 were used to observe the effect of 5,10,20 mg/L curcumin on bladder cancer cell line EJ in vitro. RESULTS: All concentrations curcumin resulted in the growth suppression significantly [Suppression ratio > or = (27.5 + 3.1)%, P < 0.05]. Above 10 mg/L concentrations curcumin induced apoptosis [Apoptosis ratio > or = (14.6 +/- 1.8)%, P < 0.05] and down-regulated of the expression of NF-kappaB [Expression ratio < or = (35.8 +/- 4.2)%, P < 0.05], Cyclin D1 [Expression ratio < or = (29.7 +/- 3.2)%, P < 0.05]. The cell phase arrest induced by curcumin was G1 phase arrest mainly with significant decrease of S phase. CONCLUSIONS: Curcumin can suppress the growth, induce apoptosis of bladder cancer EJ cell in vitro. Its mechanism is related with down-regulations of the expressions of NF-kappaB and Cyclin D1. Curcumin has great potential for the treatment of bladder cancer.

  Effects of seeding and sowing methods on the yields of root tubers of Curcuma longa.:Zhongguo Zhong Yao Za Zhi. 2005 Mar;30(6):419-21. Chinese.Li QM, Jiang RL, Lei JL, Zhang Y, Xia YL, Fang QM, Wang ZW.Sichuan Institute of Chinese Materia Medica, Chengdu 610041, China. liqingmiao@hotmail.com

 OBJECTIVE: To provide a scientific basis for standardizing the cultivation method for Curcuma longa. METHOD: Plant heights and seeding numbers were sampled periodically, the plot yields were counted a tharvested. RESULT: The effects of seeding method on yields, plant height and number were significant. The effects of different sowing ways on the yields were very little. CONCLUSION: The hole seeding method using mother tuber or blastostyle bearing three to four knots was shown to be the best may, worthy to be widely applied in production.

  Biological effects of indigenous medicinal plants Curcuma longa and Alpinia galanga.:Fitoterapia. 2005 Mar;76(2):254-7.Khattak S, Saeed-ur-Rehman , Ullah Shah H, Ahmad W, Ahmad M.Department of Chemistry, University of Peshawar, Pakistan. somiakhattak@yahoo.com

 The ethanolic extracts of Curcuma longa and Alpinia galanga exhibited excellent (100%) phytotoxic activity against Lemma minor. These extracts were also found to possess good antifungal activities against Trichophyton longifusus (65% and 60%, respectively), while in the brine shrimp lethality bioassay were found to be toxic with LD50 of 33 and 109 mincrog/ml, respectively. These extracts were found quite inert in antibacterial bioassay, while the extract from C. longa, tested for insecticidal activity, was also found to be devoid of any activity.

  Determination of curcumin in urine by capillary electrophoresis.:Se Pu. 2004 Nov;22(6):609-12. Chinese.Yuan K, Weng Q, Zhang H, Xiong J, Yang J, Xu G.National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian 116011, China.

 The major component of the plant curcuma longa (a widely cultivated tropical plant in Asia and Central America) is curcumin. Curcumin has been reported to have very strong anti-inflammatory, anti-carcinogenic, anti-oxidant, antiallergic, anti-bacterial, and anti-tumor activities. Little is known about the absorption, distribution, and metabolism of curcumin in human beings. The first step in in vivo physiological and pharmacokinetic studies is to develop a method to measure curcumin in body fluid. A rapid capillary electrophoretic (CE) method with diode array detection was established for the determination of curcumin in human urine. It could be rapidly determined within 2.5 min. The optimized experimental conditions were as follows: 15 mmol/L Na2B4O7 as buffer, applied voltage 20 kV, temperature 25 degrees C and detection wavelength 262 nm. The method has been validated and shows good performance with respect to selectivity, reproducibility and limit of detection. Curcumin had good linearity in the range of 10 - 300 mg/L, and the recoveries of curcumin added in urine were more than 96.3% with relative standard deviations (RSDs) less than 2.3%. The method is sensitive, fast and accurate and can be used to determine curcumin in urine.

  The renoprotect effect of shenhua recipe on 5/6 renal ablation rats.:Zhongguo Zhong Yao Za Zhi. 2005 Mar;30(5):377-81. Chinese.Li JJ, Chen XM, Gu Y, Wei RB, Shi SZ, Yin Z.Department of nephrology, General Hospital of PLA, Beijing 100853, China.

 OBJECTIVE: To investigate the reno protective effect of Shenhua recipe on the experimental model of 5/6 renal ablation. METHOD: 5/6 renal ablation rats were underlying this experiment. They were administered Shenhua, irbesartan respectively by gavage during 12 weeks. Body weight, systolic blood pressure, proteinuria, Scr, BUN, total protein, albumin, Glycero and cholesterol were measured. Histologic glomenular and tubulointerstitial damage scores were measured at 12 weeks. RESULT: The treated groups showed significantly less histologic glomerular and tubulointerstitial damage scores at 12 weeks. The plasma albumin were higher ( P < 0.05), urine protein excretion rates, serum cholesterol and creatinine were lower than in nontreated group, but arterial blood pressure was not significantly different in the three Shenhua treated groups compared with nontreated group. CONCLUSION: Shenhua can retard the progression of chronic renal injury in the 5/6 renal ablation without changes in systolic blood pressure.


  Nutraceuticals as anti-angiogenic agents: hopes and reality.:J Physiol Pharmacol. 2005 Mar;56 Suppl 1:51-69.Dulak J.Department of Cell Biochemistry, Faculty of Biotechnology, Jagiellonian University, Krak¨®w, Poland. jdulak@mol.uj.edu.pl.

 Angiogenesis, the formation of new blood vessels from preexisting vascular network is a driving force of organ development in ontogeny, is necessary for ovulation and hair growth, and is prerequisite for proper wound healing. It is also a critical mechanism of numerous diseases, the most important of which are cancer and atherosclerosis. Therefore, modulation of angiogenesis is considered as therapeutic strategies of great importance for human health. Numerous bioactive plant compounds, often referred to as nutraceuticals are recently tested for the potential clinical applications. Among the most frequently studied are resveratrol, a polyphenol present in red-wine and grape-seed, epigallocatechin-3-gallate (EGCG) from green tea and curcumin from Curcuma longa. It is also possible that components of other plants, including the constituents of local food diet may find application for modulation of angiogenesis, provided that their effectiveness will be confirmed in controlled, scientifically validated trials.

  Curcumin-induced histone hypoacetylation: the role of reactive oxygen species.:Biochem Pharmacol. 2005 Apr 15;69(8):1205-13.Kang J, Chen J, Shi Y, Jia J, Zhang Y.School of Life Sciences, Institute of Physics, Lanzou University, Lanzou 730000, China. kangjiuhong@lzu.edu.cn

 Curcumin (Cur), a well-known dietary pigment derived from Curcuma longa, is a promising anticancer drug, but its in vivo target molecules remain to be clarified. Here we report that exposure of human hepatoma cells to Cur led to a significant decrease of histone acetylation. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are the enzymes controlling the state of histone acetylation in vivo. Cur treatment resulted in a comparable inhibition of histone acetylation in the absence or presence of trichostatin A (the specific HDAC inhibitor), and showed no effect on the in vitro activity of HDAC. In contrast, the domain negative of p300 (a most potent HAT protein) could block the inhibition of Cur on histone acetylation; and the Cur treatment significantly inhibited the HAT activity both in vivo and in vitro. Thus, it is HAT, but not HDAC that is involved in Cur-induced histone hypoacetylation. At the same time, exposure of cells to low or high concentrations of Cur diminished or enhanced the ROS generation, respectively. And the promotion of ROS was obviously involved in Cur-induced histone hypoacetylation, since Cur-caused histone acetylation and HAT activity decrease could be markedly diminished by the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) or their combination, but not by their heat-inactivated forms. The data presented here prove that HAT is one of the in vivo target molecules of Cur; through inhibiting its activity, Cur induces histone hypoacetylation in vivo, where the ROS generation plays an important role. Considering the critical roles of histone acetylation in eukaryotic gene transcription and the involvement of histone hypoacetylation in the lose of cell viability caused by high concentrations of Cur, these results open a new door for us to further understand the molecular mechanism involved in the in vivo function of Cur.

  Establishment of high-yield suspension cell line of Curcuma zedoaria (Berg.) Rosc and study on the volatile oil synthesis-controlling with precursors.:Shi Yan Sheng Wu Xue Bao. 2004 Dec;37(6):469-74. Chinese.Wang GL, Luo HM, Fang HJ, Wu HD, Song Y.College of Life Science, Liaoning Normal University, Dalian 116029, China.

 The condition for high-yield suspension cell line and the precursors of volatile oil synthesis of Curcuma zedoaria (Berg.) Rosc were studied. The results showed that the light yellow particle callus was suitable for establishment of the high-yield suspension cell line. The optimum conditions for cell growth were MS medium added 15-30 g/L glucose and 15-30 g/L sucrose (1:1) as carbon source, the total concentration of 80 mmol/L nitrogen source combined NH4+ with NO3- (1:3), hormones of 3.0-5.0 mg/L 6-BA, 1.0 mg/L 2,4-D and dark culture after 10-15 days light culture. The 229 g/L cell (FW) and 2.11% content of volatile oil were obtained in vitro. The addition of precursors of calcium pantothenate, ammonium acetate and potassium acetate during the middle period of the cell suspension culture enhanced the volatile oil content respectively, and ammonium acetate was most effective among them. The highest yield of volatile oil obtained was 3.11% and 8.27 g/L respectively , which was 1.25 and 1.2 times of the control group.

  Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammatory agents.:Bioorg Med Chem Lett. 2005 Apr 1;15(7):1793-7.Selvam C, Jachak SM, Thilagavathi R, Chakraborti AK.Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Punjab 160 062, India.

 Curcuminoids were isolated from Curcuma longa and their pyrazole and isoxazole analogues were synthesized and evaluated for antioxidant, COX-1/COX-2 inhibitory and anti-inflammatory activities. The designed analogues significantly enhance COX-2/COX-1 selectivity and possess significant anti-inflammatory activity in carrageenan induced rat paw edema assay. Pyrazole, isoxazole analogues of curcumin (4 and 7) exhibited higher antioxidant activity than trolox. Molecular docking study revealed the binding orientations of curcumin analogues in the active sites of COX and thereby helps to design novel potent inhibitors.

  Antitumor effect and apoptosis induction in human cancer cell lines by BRM-SJS.:Ai Zheng. 2004 Nov;23(11 Suppl):1386-9. Chinese.Liu ZY, Wang ZG, Liu XJ, Tian HM, Surapol , Na DY, Zhang YF, Zhang W.Cancer Institute of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R.China.

 BACKGROUND & OBJECTIVE: It had been observed that BRM-SJS had antitumor effect in our clinical practice. This study was designed to investigate the antitumor activity of BRM-SJS, and mechanism of its action. METHODS: In vitro antitumor experiments with MTT method, meanwhile cell morphology, flow cytometry, and agarose gel electrophoresis were performed for determining apoptosis in several tumor cell lines. RESULTS: BRM-SJS had antitumor effects on human Suzhou human glioma (SHG-44), breast carcinoma (MCF-7), and human pancreas carcinoma (PANC1) in vitro, the IC50 values of BRM-SJS were 0. 299 mg/ml, 1.853 mg/ml and 9.416 mg/ml respectively. At the 2. 5 mg of BRM-SJS on SHG-44 and MCF-7, marked morphological changes, including cell shrinkage and condensation of chromosomes, were observed with electric microscope. The increase of apoptosis in SHG-44 and MCF-7 cells treated with BRM-SJS extracts 0.625 -2.5 mg for 14 -48 h was observed by Annexin-V/PI flow cytometry analysis. Agarose gel electrophoresis of DNA from SHG-44 and MCF-7 cells treated with BRM-SJS extracts 1.25 -5 mg for 24 h or 48 h showed marked DNA Ladder pattern. CONCLUSION: Antitumor activity of BRM-SJS may be related with inducement of apoptosis of tumor cells.


  Inhibitory effects of compounds from Zingiberaceae species on platelet activating factor receptor binding.:Phytother Res. 2004 Dec;18(12):1005-7.Jantan I, Pisar M, Sirat HM, Basar N, Jamil S, Ali RM, Jalil J.Department of Pharmacy, Faculty of Allied Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. ibj@medic.ukm.my

 Ten compounds isolated from Alpinia mutica Roxb., Curcuma xanthorrhiza Roxb. and Kaempferia rotunda Linn. (Family: Zingiberaceae) were investigated for their platelet-activating factor (PAF) antagonistic activities on rabbit platelets using 3H-PAF as a ligand. Among them, four compounds showed significant inhibitory effects. Alpinetin and 5,6-dehydrokawain isolated from A. mutica exhibited IC50 values of 41.6 and 59.3 microM, respectively. The IC50 values of 3-deacetylcrotepoxide and 2-hydroxy-4,4',6'-trimethoxychalcone from K. rotunda were 45.6 and 57.4 microM, respectively. 1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'-enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained from C. xanthorrhiza, showed an IC50 value of 40.9 microM. The results indicated that these compounds were relatively strong PAF receptor binding inhibitors.

  Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice.:J Agric Food Chem. 2005 Feb 23;53(4):959-63.

 Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human health. The chemistry includes curcuminoids and sesquiterpenoids as components, which are known to have antioxidative, anticarcinogenic, and antiinflammatory activities. In this study, we investigated the effects of three turmeric extracts on blood glucose levels in type 2 diabetic KK-A(y) mice (6 weeks old, n = 5/group). These turmeric extracts were obtained by ethanol extraction (E-ext) to yield both curcuminoids and sesquiterpenoids, hexane extraction (H-ext) to yield sesquiterpenoids, and ethanol extraction from hexane-extraction residue (HE-ext) to yield curcuminoids. The control group was fed a basal diet, while the other groups were fed a diet containing 0.1 or 0.5 g of H-ext or HE-ext/100 g of diet or 0.2 or 1.0 g of E-ext/100 g of diet for 4 weeks. Although blood glucose levels in the control group significantly increased (P < 0.01) after 4 weeks, feeding of 0.2 or 1.0 g of E-ext, 0.5 g of H-ext, and 0.5 g of HE-ext/100 g of diet suppressed the significant increase in blood glucose levels. Furthermore, E-ext stimulated human adipocyte differentiation, and these turmeric extracts had human peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand-binding activity in a GAL4-PPAR-gamma chimera assay. Also, curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone had PPAR-gamma ligand-binding activity. These results indicate that both curcuminoids and sesquiterpenoids in turmeric exhibit hypoglycemic effects via PPAR-gamma activation as one of the mechanisms, and suggest that E-ext including curcuminoids and sesquiterpenoids has the additive or synergistic effects of both components.

  Numerical taxonomy of medicinal plants of Curcuma in China.:Zhongguo Zhong Yao Za Zhi. 2004 Jan;29(1):15-24. Chinese.Xiao XH, Zhong GY, Shu GM, Li LY, Fang QM, Chen SY, Shu ZW.Department of Pharmacy, 302 Hospital of PLA, Beijing 100039, China.

 OBJECTIVE: To provide some new evidences for the classfication and identification of medicinal plants of Curcuma. METHOD: A numerical taxonomy by means of cluster analysis and principal Component analysis is used. Combined with RAPD analysis, computer image analysis and chemical analysis, the taxonomical relationships of the plants of Curcuma in China were characterized qualitatively and quantitatively. RESULT AND CONCLUSION: The plants of Curcuma is systematized into 9 species, 1 species complex, 3 cultivated varieties. A lot of taxonomic confusion and disputations were consequently expounded.

  Histological and morphological studies on the rhizomes of Curcuma.:Zhongguo Zhong Yao Za Zhi. 2004 May;29(5):395-9. Chinese.Xiao XH, Shu GM, Li LY, Fang QM, Xia WJ, Su ZW.Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing 100039, China. pharmacy302@sohu.com

 OBJECTIVE: To provide some new evidences for the identification of medicinal materials of Curcuma. METHOD: Microscopic observation was made to characterize the rhizomes of Curcuma. RESULT AND CONCLUSION: There were no obvious histological and morphological differences among the rhizomes of Curcuma. The distribution of oil cells and vascular bundles as well as the number and diameter of xylem vessels were considered to be the distinguishing features of their rhizomes.

  Histological and morphological studies on leaves of Curcuma in China.:Zhongguo Zhong Yao Za Zhi. 2004 Mar;29(3):203-7. Chinese.Xiao XH, Zhao YL, Jin C, Shu GM, Fang QM, Shu ZW.Department of Pharmacy, 302 Hospital of People's Liberation A, Beijing 100039, China. pharmacy302@sohu.com

 OBJECTIVE: To provide some new evidences for the classification and identification of medicinal materials of Curcuma. METHOD: The optical microscope and electronic microsccopic scaning were used to characterize the leaves of Curcuma. RESULT AND CONCLUSION: There were no obvious histological and morphological differences among the leaves of Curcuma. But the differences in the hair distribution, stoma density and size , shape and size of epidermic cells could be considered to be the main features for the microscopic identification of leaves of Curcuma.


  Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study.:J Altern Complement Med. 2004 Dec;10(6):1015-8.Bundy R, Walker AF, Middleton RW, Booth J.Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, Reading, UK. r.bundy@reading.ac.uk

 OBJECTIVES: To assess the effects of turmeric (Curcuma longa) extract on irritable bowel syndrome (IBS) symptomology in otherwise healthy adults. DESIGN: Partially blinded, randomized, two-dose, pilot study. SUBJECTS: Five hundred (500) volunteers were screened for IBS using the Rome II criteria. Two hundred and seven (207) suitable volunteers were randomized. INTERVENTIONS: One or two tablets of a standardized turmeric extract taken daily for 8 weeks. OUTCOMES MEASURES: IBS prevalence, symptom-related quality of life (IBSQOL) and self-reported effectiveness. RESULTS: IBS prevalence decreased significantly in both groups between screening and baseline (41% and 57%), with a further significant drop of 53% and 60% between baseline and after treatment, in the one- and two-tablet groups respectively (p < 0.001). A post-study analysis revealed abdominal pain/discomfort score reduced significantly by 22% and 25% in the one- and two-tablet group respectively, the difference tending toward significance (p = 0.071). There were significant improvements in all bar one of the IBSQOL scales of between 5% and 36% in both groups, approximately two thirds of all subjects reported an improvement in symptoms after treatment, and there was a favorable shift in self-reported bowel pattern. There were no significant differences between groups. CONCLUSIONS: Turmeric may help reduce IBS symptomology. Placebo controlled trials are now warranted to confirm these findings.

  Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity.:Basic Clin Pharmacol Toxicol. 2005 Jan;96(1):80-7. Wattanapitayakul SK, Chularojmontri L, Herunsalee A, Charuchongkolwongse S, Niumsakul S, Bauer JA.Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand. suvara@swu.ac.th

 Doxorubicin is an important and effective anticancer drug widely used for the treatment of various types of cancer but its clinical use is limited by dose-dependent cardiotoxicity. Elevated tissue levels of cellular superoxide anion/oxidative stress are a mechanism by which doxorubicin-induced cardiotoxicity. Selected medicinal plant extracts were tested for their antioxidant capacity and cardioprotective effect against doxorubicin-induced cardiotoxicity. The cardiac myoblasts H9c2 were incubated with the antioxidants ascorbic acid, trolox, N-acetylcysteine or selected medicinal plant extracts including; 1) ethanolic extracts from Curcuma longa L-EtOH Phyllanthus emblica L-EtOH, and Piper rostratum Roxb-EtOH; and 2) water extracts from Curcuma longa L-H2O and Morus alba L-H2O. The cardioprotective effects of these extracts were evaluated by crystal violet cytotoxicity assay. IC50s of doxorubicin were compared in the presence or absence of ascorbic acids, trolox, N-acetylcysteine or plant extracts. Morus alba L-H2O showed the highest antioxidant properties evaluated by ferric reducing/antioxidant power assay. Ascorbic acid and N-acetylcysteine had modest effects on the protection of doxorubicin-induced cytotoxicity while trolox showed insignificant protective effect. All plant extracts protected cardiac toxicity at different degrees except that Curcuma longa L-EtOH had no protective effect. Phyllanthus emblica-EtOH (100 microg/ml) showed the highest cardioprotective effect (approximately 12-fold doxorubicin IC50 increase). The data demonstrate that antioxidants from natural sources may be useful in the protection of cardiotoxicity in patients who receive doxorubicin.

  Increased radiation sensitivity of an eosinophilic cell line following treatment with epigallocatechin-gallate, resveratrol and curcuma.:Int J Mol Med. 2005 Feb;15(2):337-52.Baatout S, Derradji H, Jacquet P, Mergeay M.Laboratory of Radiobiology, Belgian Nuclear Research Center, B-2400 Mol, Belgium. sbaatout@sckcen.be

 Ionizing radiation is widely used in radiotherapy, in order to promote an apoptotic response in cancerous cells. Since the need to find new substances that would enhance the radiation-induced apoptosis in cancerous cells is great, we studied the effect of epigallocatechin-gallate (EGCG, a tea component), resveratrol (a wine component) and curcuma on cell proliferation and radiation-induced apoptosis in the human leukaemic cell line, EOL-1, derived from a patient with eosinophilic leukaemia. Cells were X-irradiated with 0, 2, 4, 6 or 8 Gy and cultured in the presence of EGCG, resveratrol or curcuma (concentrations ranging from 0 to 200 microM) for 1, 2 or 3 days of culture. Cell proliferation was measured using trypan blue exclusion. Apoptosis was evaluated using light microscopy (morphology study after May-Grunwald Giemsa staining) and flow cytometry (annexin-V staining). Irradiation alone induced a dose-related reduction in cell proliferation and the appearance of polyploid cells in EOL-1 cells. Additionally, EOL-1 cells underwent a dose-related increase of apoptosis which, from the second day on, was accompanied by a dose-related increase of necrosis. When cells were exposed to EGCG, resveratrol or curcuma alone, a decrease in cell proliferation was observed, beginning from 25 microM EGCG and 50 microM resveratrol and curcuma, while an increase in the percentage of apoptotic cells was noted from 50 microM EGCG, 100 microM resveratrol and curcuma in EOL-1 cells, after only one day of culture. Simultaneous exposure to X-irradiation and, EGCG, resveratrol or curcuma resulted in a synergistic decrease of cell proliferation as well as in a synergistic increase of apoptosis and necrosis. These results suggest that, depending on the concentration, EGCG, resveratrol and curcuma enhance radiation-induced apoptosis in the leukaemic cell line, EOL-1 (EGCG >resveratrol >curcuma). In order to further characterise the radiation-induced apoptosis of this leukaemic cell line, other flow cytometrical analyses are in progress.

  A curcuminoid and two sesquiterpenoids from Curcuma zedoaria as inhibitors of nitric oxide synthesis in activated macrophages.:Arch Pharm Res. 2004 Dec;27(12):1220-5.Jang MK, Lee HJ, Kim JS, Ryu JH.College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Korea.

 The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) is known to be responsible for vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment of inflammatory diseases accompanied by overproduction of NO. In the course of screening oriental anti-inflammatory herbs for the inhibitory activity of NO synthesis, a crude methanolic extract of Curcuma zedoaria exhibited significant activity. The activity-guided fractionation and repetitive chromatographic procedures with the EtOAc soluble fraction allowed us to isolate three active compounds. They were identified as 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one (1), procurcumenol (2) and epiprocurcumenol (3) by spectral data analyses. Their concentrations for the 50% inhibition of NO production (IC50) in lipopolysaccharide (LPS)-activated macrophages were 8, 75, 77 microM, respectively. Compound 1 showed the most potent inhibitory activity for NO production in LPS-activated macrophages, while the epimeric isomers, compound 2 and 3 showed weak and similar potency. Inhibition of NO synthesis by compound 1 was very weak when activated macrophages were treated with 1 after iNOS induction. In the immunoblot analysis, compound 1 suppressed the expression of iNOS in a dose-dependent manner. In summary, 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one from Curcuma zedoaria inhibited NO production in LPS-activated macrophages through suppression of iNOS expression. These results imply that the traditional use of C. zedoaria rhizome as anti-inflammatory drug may be explained at least in part, by inhibition of NO production.

  Hepatoprotective effect of sesquiterpenes in turmeric.:Biofactors. 2004;21(1-4):167-70.

 Hepatoprotective effect of turmeric together with its sesquiterpenes and curcuminoids fractions were examined on D-galactosamine induced liver injury in rats. All the diets individually contained the turmeric extract, the curcuminoids fraction, and the sesquiterpenes fraction suppressed the increase of LDH, ALT, and AST levels caused by D-GalN treatment. Since few anti-oxidative activities are expected in the sesquiterpenes fraction, it is presumed that hepatoprotective mechanism of sesquiterpenes in turmeric is different from that of curuminoids.


  A novel formulation design about water-insoluble oily drug: preparation of zedoary turmeric oil microspheres with self-emulsifying ability and evaluation in rabbits.:Int J Pharm. 2005 Jan 20;288(2):315-23. Epub 2004 Dec 8.You J, Cui FD, Li QP, Han X, Yu YW, Yang MS.Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.

 To enhance in vivo absorption of zedoary turmeric oil (ZTO) and develop new formulations of a water-insoluble oily drug, novel ZTO microspheres with self-emulsifying ability, called self-emulsifying microspheres here, were prepared in a liquid system by the quasi-emulsion solvent diffusion method. The microspheres containing hydroxypropyl methylcellulose acetate succinate (HPMCAS-LG), Talc and Aerosil 200 formed the stable surfactant-free emulsion when exposed to the pH 6.8 phosphate buffer, and were significantly different from the conventional self-emulsifying systems (SES), defined as isotropic mixtures of oil, surfactant and drug. Micromeritic properties, the efficiency of emulsification and the drug-release rate of the resultant microspheres were investigated. The bioavailability of the microspheres to the conventional self-emulsifying formulation for oral administration was evaluated in 12 healthy rabbits. A HPLC method was employed to determine the plasma concentration of Germacrone, an indexical component found in ZTO. The release rates of ZTO and Germacrone from the microspheres were enhanced significantly with increasing amounts of dispersing agents, and the efficiency of self-emulsification greatly depended on the HPMCAS-LG/Aerosil 200 ratio. The emulsion droplets released from the microspheres were much smaller than that of the conventional SES. The microsphere bioavailability (F) to the conventional SES for oral administration was 157.7%. Our method greatly improved the bioavailability of the water-insoluble oily drug from the self-emulsifying microspheres over the conventional SES and it is useful for the oily drug to form solid preparations.

  Induction of apoptosis in human nasopharyngeal carcinoma cell line CNE-2Z by curcumin.:Ai Zheng. 2004 Dec;23(12):1651-4. Chinese.Liang T, Chen MJ, Zhou KY, Tang XD, Wang XG.Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China. liangt@gdmc.edu.cn

 BACKGROUND & OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China. Radiotherapy is a major therapy for NPC in early phase,while proper chemotherapy is necessary for NPC in late phase. Some chemotherapeutic drugs have been used to treat tumors by inducing apoptosis of tumor cells. This study was to investigate effects of curcumin on proliferation,and apoptosis of NPC cell line CNE-2Z. METHODS: CNE-2Z cells were treated with different concentrations of curcumin, inhibition rates of cell proliferation,and IC(50) of curcumin were detected by MTT method. Cell apoptosis was analyzed by flow cytometry (FCM), agarose gel electrophoresis,and Hoechst33258-PI fluorescence staining. RESULTS: Proliferation of CNE-2Z cells was inhibited obviously by curcumin in dose- and time-dependent manners. IC(50) of curcumin to CNE-2Z cells at 24,48,and 72 h were (24.05+/-0.47),(19.20+/-0.17),and (7.35+/-0.50) micromol/L, respectively. After treated with 5,10,and 20 micromol/L of curcumin for 24 h, apoptotic rates of CNE-2Z cells were (4.9+/-3.2)%,(10.7+/-2.7)%, and (14.7+/-0.5)%, respectively. After treated with 10,20 micromol/L of curcumin for 24 h, morphologic changes, such as chromatin shrinkage,nuclear condensation,and chromatin fragmentation,were observed in CNE-2Z cells by fluorescent staining, a fragmented DNA ladder was detected by electrophoresis. CONCLUSION: Curcumin may induce apoptosis, and inhibit proliferation of CNE-2Z cells.

  Study on the SFE condition for curcumin in Curcuma longa.:Zhongguo Zhong Yao Za Zhi. 2004 Sep;29(9):857-60. Chinese.Su SL, Wu QN, Ouyang Z, Wu DK, Chen J.Department of Pharmaceutical Engineering of Jiangsu University, Zhenjian 212013 China. lyhssl@ujs.edu.cn

 OBJECTIVE: To optimize the conditions of supercritical fluid extraction (SFE) for curcumin in Curcuma longa. METHOD: Optimum extraction conditions were studied by orthogonal tests. The extracts were analyzed by HPLC. RESULT: The optimal extraction conditions were pressure 25 MPa, temperature 55 degrees C, static time 4 h, dynamic time 5 h, flow rate of CO2 3.5 L x min(-1), co-solvent ethanol 30% (mL x g(-1)). CONCLUSION: It is feasible to extract curcumin by SFE.

  Botanical medicine and cancer: a review of the safety and efficacy.:Expert Opin Pharmacother. 2004 Dec;5(12):2485-501. Review.Boon H, Wong J.Leslie Dan Faculty of Pharmacy, Toronto, ON M5S 2S2, Canada. heather.boon@utoronto.ca

 It is currently estimated that > 50% of all patients diagnosed with cancer explore complementary and alternative medicine - especially herbal medicine. We conducted a comprehensive review to assess the safety and efficacy of herbal medicines commonly used by patients in an attempt to: prevent cancer; treat cancer; and treat adverse effects associated with conventional cancer treatments. Current evidence suggests that Asian ginseng, garlic, green tea, tomatoes and soy intake as part of the diet may be useful in preventing various cancers; additional research is needed in order to determine the efficacy of essiac, evening primrose oil, mistletoe, reishi, shiitake and turmeric as cancer treatments; and ginger may be effective in treating chemotherapy-induced nausea and vomiting.

  Curcumin, the active constituent of turmeric, inhibits amyloid peptide-induced cytochemokine gene expression and CCR5-mediated chemotaxis of THP-1 monocytes by modulating early growth response-1 transcription factor.:J Neurochem. 2004 Dec;91(5):1199-210.Giri RK, Rajagopal V, Kalra VK.Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA.

 Epidemiological studies show reduced risk of Alzheimer's disease (AD) among patients using non-steroidal inflammatory drugs (NSAID) indicating the role of inflammation in AD. Studies have shown a chronic CNS inflammatory response associated with increased accumulation of amyloid peptide and activated microglia in AD. Our previous studies showed that interaction of Abeta1-40 or fibrilar Abeta1-42 caused activation of nuclear transcription factor, early growth response-1 (Egr-1), which resulted in increased expression of cytokines (TNF-alpha and IL-1beta) and chemokines (MIP-1beta, MCP-1 and IL-8) in monocytes. We determined whether curcumin, a natural product known to have anti-inflammatory properties, suppressed Egr-1 activation and concomitant expression of cytochemokines. We show that curcumin (12.5-25 microm) suppresses the activation of Egr-1 DNA-binding activity in THP-1 monocytic cells. Curcumin abrogated Abeta1-40-induced expression of cytokines (TNF-alpha and IL-1beta) and chemokines (MIP-1beta, MCP-1 and IL-8) in both peripheral blood monocytes and THP-1 cells. We found that curcumin inhibited Abeta1-40-induced MAP kinase activation and the phosphorylation of ERK-1/2 and its downstream target Elk-1. We observed that curcumin inhibited Abeta1-40-induced expression of CCR5 but not of CCR2b in THP-1 cells. This involved abrogation of Egr-1 DNA binding in the promoter of CCR5 by curcumin as determined by: (i) electrophoretic mobility shift assay, (ii) transfection studies with truncated CCR5 gene promoter constructs, and (iii) chromatin immunoprecipitation analysis. Finally, curcumin inhibited chemotaxis of THP-1 monocytes in response to chemoattractant. The inhibition of Egr-1 by curcumin may represent a potential therapeutic approach to ameliorate the inflammation and progression of AD.


  Xanthorrhizol, a natural sesquiterpenoid from Curcuma xanthorrhiza, has an anti-metastatic potential in experimental mouse lung metastasis model.:Biochem Biophys Res Commun. 2005 Jan 7;326(1):210-7.Choi MA, Kim SH, Chung WY, Hwang JK, Park KK.Brain Korea 21 Project for Medical Science, Yonsei University, Seoul 120-752, Republic of Korea

 Xanthorrhizol is a sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhiza. In this study, the anti-metastatic activity of xanthorrhizol was evaluated by using an in vivo mouse lung metastasis model and a tumor mass formation assay. Interestingly, xanthorrhizol dramatically inhibited the formation of tumor nodules in the lung tissue and the intra-abdominal tumor mass formation. Next, to examine the mechanism of the anti-metastatic action of xanthorrhizol in the mouse lung metastasis, expression patterns of the several intracellular signaling molecules were evaluated using the lung tissues with tumor nodules. Higher expression levels of cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), and phosphorylated extracellular signal-regulated kinase (ERK) were observed in the metastatic group compared with control, but these were attenuated by the treatment of xanthorrhizol. In conclusion, xanthorrhizol exerts anti-metastatic activity in vivo and this effect could be highly linked to the metastasis-related multiplex signal pathway including ERK, COX-2, and MMP-9

  Antioxidant availability of turmeric in relation to its medicinal and culinary uses.:Phytother Res. 2004 Oct;18(10):798-804.Tilak JC, Banerjee M, Mohan H, Devasagayam TP.Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.

 Turmeric (Curcuma longa) has been used in Indian cooking, and in herbal remedies. Its possible mechanism of action was examined in terms of antioxidant availability during actual cooking conditions and in therapeutic applications using standardized extracts. The assays involve different levels of antioxidant action such as oxygen radical absorbance capacity (ORAC), radical scavenging abilities using 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2'-azobis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP) and protection of membranes examined by inhibition of lipid peroxidation besides the content of phenols and total flavonoids. The aqueous and ethanol extracts of two major preparations of turmeric, corresponding to its use in cooking and medicine, showed significant antioxidant abilities. In conclusion, the studies reveal that the ability of turmeric to scavenge radicals, reduce iron complex and inhibit peroxidation may explain the possible mechanisms by which turmeric exhibits its beneficial effects in relation to its use in cooking and medicine.

  Antihyperglycaemic and antioxidant effect of hyponidd, an ayurvedic herbomineral formulation in streptozotocin-induced diabetic rats.:J Pharm Pharmacol. 2004 Nov;56(11):1435-42.Babu PS, Stanely Mainzen Prince P.Department of Biochemistry, Annamalai University, Annamalai Nagar-608 002, Tamil Nadu, India.

 Hyponidd is a herbomineral formulation composed of the extracts of ten medicinal plants ( Momordica charantia, Melia azadirachta, Pterocarpus marsupium, Tinospora cordifolia , Gymnema sylvestre, Enicostemma littorale, Emblica officinalis, Eugenia jambolana, Cassia auriculata and Curcuma longa). We have investigated hyponidd for its possible antihyperglycaemic and antioxidant effect in diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg kg(-1) body weight). Oral administration of hyponidd (100 mg kg(-1) and 200 mg kg(-1)) for 45 days resulted in significant lowered levels of blood glucose and significant increased levels of hepatic glycogen and total haemoglobin. An oral glucose tolerance test was also performed in experimental diabetic rats in which there was a significant improvement in blood glucose tolerance in the rats treated with hyponidd. Hyponidd administration also decreased levels of glycosylated haemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and alpha-tocopherol in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of hyponidd. The effect of hyponidd at a dose of 200 mg kg(-1) was more effective than glibenclamide (600 microg kg(-1)) in restoring the values to near normal. The results showed that hyponidd exhibits antihyperglycaemic and antioxidant activity in STZ-induced diabetic rats.

  Study on releasing rate of chrysophanol from Ruyi Jinhuang plaster.:Zhongguo Zhong Yao Za Zhi. 2004 Aug;29(8):746-7, 816. Chinese.Mao P, Xu J, Wu YM.Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

 OBJECTIVE: To study the releasing rate of chrysophanol from Ruyi Jinhuang plaster. METHOD: Based on the detecting methods of releasing rate and residual dosage applied in (Pharmacopoeia of P. R. C) (2000 edition), the contents of chrysophanol were detected by HPLC. RESULT: Chrysophanol in Ruyi Jinhuang plaster could well be released from plaster and to form medicinal concentration gradient. CONCLUSION: Chrysophanol in Ruyi-Jinhuang plaster can possibly be absorbed by skin.

  Anti-allergic principles from Thai zedoary: structural requirements of curcuminoids for inhibition of degranulation and effect on the release of TNF-alpha and IL-4 in RBL-2H3 cells.:Bioorg Med Chem. 2004 Nov 15;12(22):5891-8.

 The 80% aqueous acetone extract of the rhizomes of Curcuma zedoaria cultivated in Thailand (Thai zedoary) was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation, in RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. From the active fraction, four curcuminoids (curcumin, dihydrocurcumin, tetrahydrodemethoxycurcumin, and tetrahydrobisdemethoxycurcumin) were isolated together with two bisabolane-type sesquiterpenes, and the effects of four curcuminoids from Thai zedoary and several related compounds on the degranulation were examined. Among them, curcumin showed the highest activity against beta-hexosaminidase release with IC(50) of 5.3 microM, followed by bisdemethoxycurcumin (IC(50) = 11 microM). With regard to the structural requirements of curcuminoids for the activity, the conjugated olefins at the 1-7 positions and the 4'- or 4''-hydroxyl groups of curcuminoids were suggested to be essential for the strong activity, whereas the 3'- or 3''-methoxyl group only enhanced the activity. Furthermore, effects of curcumin and bisdemethoxycurcumin on calcium ionophores (A23187 and ionomycin)-induced degranulation and antigen-induced release of TNF-alpha and IL-4 were examined.


  Antimicrobial activity of ultrasound-assisted solvent-extracted spices.:Lett Appl Microbiol. 2004;39(5):401-6.Thongson C, Davidson PM, Mahakarnchanakul W, Weiss J.Department of Food Science and Technology, Kasetsart University, Jatujak, Bangkok, Thailand.

 AIMS: The objective of this research was to determine the antimicrobial activity of conventional and high-intensity ultrasound-assisted (HI-US) solvent-extracted Thai spices, including ginger (Zingiber officinale Rose), fingerroot (Bosenbergia pandurata Holtt) and turmeric (Curouma longa Linn). METHODS AND RESULTS: Extracts were obtained using hexane, isopropanol and a 7 : 3 isopropanol : hexane mixture as solvents with and without HI-US. The antimicrobial activity of the extracts was assayed against four strains each of Listeria monocytogenes and Salmonella Typhimurium DT 104 using an agar dilution assay. Application of HI-US did not alter antibacterial activity against S. Typhimurium, but antilisterial activity of some HI-US spice extracts decreased. Solvent type affected antimicrobial efficacy of extracts with hexane producing the least antimicrobial activity. Fingerroot extracted with isopropanol-hexane and without HI-US had the best antilisterial effect while HI-US-isopropanol fingerroot extract had the greatest antimicrobial efficacy against S. Typhimurium. CONCLUSIONS: Application of HI-US reduced time of extraction to 5 min, compared with the 24 h required for conventional extraction and maintained antimicrobial activity against Salmonella but slightly reduced activity against Listeria. SIGNIFICANCE AND IMPACT OF THE STUDY: HI-US in combination with proper solvent selection may offer a new tool to optimize extraction of spice essential oil for use as antimicrobial agents, and reduce processing time and costs.

  Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from Turmeric powder.:Biochem Pharmacol. 2004 Nov 15;68(10):2043-52.Chearwae W, Anuchapreeda S, Nandigama K, Ambudkar SV, Limtrakul P.Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

 P-glycoprotein (Pgp, ABCB1) is an ATP-dependent drug efflux pump linked to development of multidrug resistance (MDR) in cancer cells. Previously [Biochem Pharmacol 2002;64:573-82], we reported that a curcumin mixture could modulate both function and expression of Pgp. This study focuses on the effect of three major curcuminoids--curcumin I, II and III purified from a curcumin mixture--on modulation of Pgp function in a multidrug resistant human cervical carcinoma cell line (KB-V1). The similar IC(50) values for cytotoxicity of curcuminoids of KB-V1, and KB-3-1 (parental drug sensitive cell line) suggest that these curcuminoids may not be substrates for Pgp. Treating the cells with non-toxic doses of curcuminoids increased their sensitivity to vinblastine only in the Pgp expressing drug resistant cell line, KB-V1, and curcumin I retained the drug in KB-V1 cells more effectively than curcumin II and III, respectively. Effects of each curcuminoid on rhodamine123, calcein-AM, and bodipy-FL-vinblastine accumulation confirmed these findings. Curcumin I, II and III increased the accumulation of fluorescent substrates in a dose-dependent manner, and at 15 microM, curcumin I was the most effective. The inhibitory effect in a concentration-dependent manner of curcuminoids on verapamil-stimulated ATPase activity and photoaffinity labeling of Pgp with the [(125)I]-iodoarylazidoprazosin offered additional support; curcumin I was the most potent modulator. Taken together, these results indicate that curcumin I is the most effective MDR modulator among curcuminoids, and may be used in combination with conventional chemotherapeutic drugs to reverse MDR in cancer cells.

  Evaluation of DNA damage in mice topically exposed to total particulate matter from mainstream and sidestream smoke from cigarettes and bidis.:Mutagenesis. 2004 Sep;19(5):413-21.Thapliyal R, Dolas SS, Pakhale SS, Maru GB.Tobacco Carcinogenesis Group, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai-410 208, India.

 The genotoxic potential of total particulate matter (TPM) from mainstream smoke (MS) and sidestream smoke (SS) of Indian smoking products, namely cigarettes and bidis, as well as a brand of US cigarettes, was studied by determining the levels of bulky aromatic DNA adducts in mouse tissues. TPM from MS or SS of various smoking products [equal weights (2.5 mg) or the amount derived from equal (0.25) cigarette/bidi] was applied topically to mouse skin once a day for four consecutive days and adduct levels were determined in DNA from skin and lung by (32)P-post-labelling analysis. Relatively higher levels of bulky aromatic DNA adducts were noted in mouse skin treated with MS from a single Indian non-filter (INF) cigarette when compared with MS of a single bidi (with about half the product weight and one-quarter the tobacco compared with a cigarette), while comparable adduct levels were noted with SS from these two products. Considering the differences in the yields of constituents of tobacco smoke from the different products analyzed, the genotoxic potential of INF, Indian filter king (IFK) and American filter (AF) cigarettes as well as bidis was determined by topically applying an equal amount of TPM (rather than equal product-derived TPM). SS-derived TPM from all the products showed relatively higher levels of total polycyclic aromatic hydrocarbons and induced relatively higher levels of bulky aromatic DNA adducts than those derived from MS. The data indicate that TPM (MS + SS) from cigarettes appears to be more genotoxic than that from bidis and the contribution of tendu leaf (a non-tobacco bidi wrapper) to the generation of bulky aromatic DNA adducts appears to be significant, particularly in SS of bidis. Topical pretreatment with curcumin decreased the levels of TPM-derived adducts while pretreatment with dietary turmeric failed to show such protection.

  Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2.:Mol Cancer Ther. 2004 Sep;3(9):1101-8.Syng-Ai C, Kumari AL, Khar A.Center for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.

 Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited growth of several types of malignant cells both in vivo and in vitro. However, its mechanism of action still remains unclear. In this study, we have focused primarily on the cytotoxic effects of curcumin on three human tumor cell lines and rat primary hepatocytes. Curcumin induced apoptosis in MCF-7, MDAMB, and HepG2 cells in a dose-dependent and time-dependent manner. Apoptosis was mediated through the generation of reactive oxygen species. Attempts were made to establish the role played by endogenous glutathione on the apoptotic activity of curcumin. Depletion of glutathione by buthionine sulfoximine resulted in the increased generation of reactive oxygen species, thereby further sensitizing the cells to curcumin. Interestingly, curcumin had no effect on normal rat hepatocytes, which showed no superoxide generation and therefore no cell death. These observations suggest that curcumin, a molecule with varied actions, could be developed into an effective chemopreventive and chemotherapeutic agent.

  A water extract of Curcuma longa L. (Zingiberaceae) rescues PC12 cell death caused by pyrogallol or hypoxia/reoxygenation and attenuates hydrogen peroxide induced injury in PC12 cells.:Life Sci. 2004 Sep 24;75(19):2363-75.Koo BS, Lee WC, Chung KH, Ko JH, Kim CH.Department of Biochemistry, Molecular Biology and Neurobiology, College of Oriental Medicine, DongGuk University, Kyungju City, Kyungbuk 780-714, Republic of Korea.

 A number of studies indicate that free radicals are involved in the neurodegeneration in Alzheimer's disease (AD). The role of superoxide anion (O2*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O2*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O2*-, as assessed by O2*- sensitive fluorescent precursor hydroethidine (HEt). A water extract of Curcuma longa L. (Zingiberaceae) (CLE), having O2*- scavenging activity rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by CLE. The present study was also conducted to examine the effect of CLE on H2O2 -induced toxicity in rat pheochromocytoma line PC12 by measuring cell lesion, level of lipid peroxidation and antioxidant enzyme activities. Following a 30 min exposure of the cells to H2O2 (150 microM), a marked decrease in cell survival, activities of glutathione peroxidase and catalase as well as increased production of malondialdehyde (MDA) were found. Pretreatment of the cells with CLE (0.5-10 microg/ml) prior to H2O2 exposure significantly elevated the cell survival, antioxidant enzyme activities and decreased the level of MDA. The above-mentioned neuroprotective effects are also observed with tacrine (THA, 1 microM), suggesting that the neuroprotective effects of cholinesterase inhibitor might partly contribute to the clinical efficacy in AD treatment. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O2*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury.


  Antimicrobial activity and cytotoxicity of the essential oil of Curcuma zedoaria.:Am J Chin Med. 2004;32(2):281-90.Lai EY, Chyau CC, Mau JL, Chen CC, Lai YJ, Shih CF, Lin LL.Department of Nursing, Hungkuang University, Taichung 433-2, Taiwan.

 The chemical compositions of the essential oil of Curcuma zedoaria (Berg.) Rosc. were analyzed by gas chromatography-mass spectrometry (GC-MS) and showed a high content of epicurzerenone and curdione representing 46.6% and 13.7% of the total oil, respectively. The essential oil was evaluated for potential antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonasa aeruginosa, Vibrio parahaemolyticus, Salmonella typhimurium and Bacillus cereus. V. parahaemolyticus was sensitive to the presence of the essential oil, while the most resistant strain appeared to be E. coli. Based on 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay, nitroblue tetrazolium (NBT) reduction and cell morphology, the essential oil of C. zedoaria could inhibit the proliferation of human promyelocytic leukemia HL-60 cells. These results suggest that the essential oil has the antimicrobial activity against some of Gram- positive and negative pathogenic microorganisms and the components of the extract lead to the apoptosis of human cancer cell line.

  Reversal of resistance to adriamycin in human breast cancer cell line MCF-7/ADM by beta-elemene.:Zhonghua Zhong Liu Za Zhi. 2004 May;26(5):268-70. Chinese.Hu J, Jin W, Yang PM.Dalian Medical University, Dalian 116027, China.

 OBJECTIVE: To study the reversal mechanism of adriamycin (ADM) resistance in human breast cancer cell line MCF-7/ADM by beta-elemene (beta-ELE), a wide spectrum anticancer drug derived from the Chinese herb Curcuma chaeocaulis. METHODS: Sensitivity to ADM of MCF-7/ADM cells was studied by MTT assay. Intracellular accumulation of ADM in MCF-7/ADM cells was observed by fluorescent-spectrophotometry. Expression of bcl-2 protein was detected by flow cytometry. RESULTS: A non-cytotoxic dose (6 micro g/ml) and a weakly cytotoxic dose (13 micro g/ml) of beta-ELE could significantly enhance the cytotoxic effects of ADM on MCF-7/ADM cells to 1.4 and 2.2 fold as compared to the beta-ELE untreated control cells. The intracellular concentration of ADM in MCF-7/ADM cells was significantly increased after treatment with beta-ELE (P < 0.01). The expression of bcl-2 protein in MCF-7/ADM cells was reduced from 90.2% to 70.0% (P < 0.05). CONCLUSION: beta-ELE could partially reverse the drug resistance to ADM in MCF-7/ADM, which is related to the increased accumulation of intracellular ADM and the decreased expression of bcl-2.

  Safety of Curcuma aromatica oil gelatin microspheres administered via hepatic artery.:World J Gastroenterol. 2004 Sep 15;10(18):2637-42.Deng SG, Wu ZF, Li WY, Yang ZG, Chang G, Meng FZ, Mo LL.Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510120, 111 Dade Road, Guangdong Province, China. dengshigui@yahoo.com.cn

 AIM: To evaluate the safety of Curcuma aromatica oil gelatin microspheres (CAO-GMS) infused via hepatic artery against primary liver cancer. METHODS: The safety of CAO-GMS was evaluated in view of its acute toxicity in rats, long-term toxicity in Beagle dogs and general pharmacology in rats and mongrel dogs. RESULTS: The 50% lethal dose (LD50) of CAO-GMS infused via the hepatic artery was 17.19 mg/kg, and the serum biochemical indices of dying rats after the administration changed markedly while those of survived rats did not. Subsequent pathological examination of the tissues from the dead rats indicated improper embolism. Similar edema and small necrotic foci in the hepatic lobule were found in the hepatic tissue of rats receiving 10 and 5 mg/kg CAO-GMS and GMS 60 d after the last administration, while not in the rats of the blank control group, indicating that microspheres infused via the hepatic artery may induce irreversible liver damage dose-dependently. General pharmacological study showed that the activities (posture and gait), respiration frequency, blood pressure or heart rate of the dogs were not affected by CAO-GMS, nor were salivation, tremor or pupil changes of the rats observed or their balancing ability compromised, suggesting CAO-GMS infused via the hepatic artery did not significantly affect the nervous, respiratory and cardiovascular systems. CONCLUSION: CAO-GMS embolization administered via the hepatic artery is safe but undesired embolization induced by vascular variation should be given due attention in its clinical application. Individualized embolization dosage and super-selective catheterization technique are recommended to avoid undesired embolism and reduce complications.

  Protective effects of Curcuma longa on ischemia-reperfusion induced myocardial injuries and their mechanisms.:Life Sci. 2004 Aug 20;75(14):1701-11.Mohanty I, Singh Arya D, Dinda A, Joshi S, Talwar KK, Gupta SK.Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029.

 The present study was undertaken to evaluate the cardioprotective potential of Curcuma longa (Turmeric) in the ischemia-reperfusion (I/R) model of myocardial infarction (MI). Wistar rats were divided into three groups and received saline orally (sham, control I/R group) and Curcuma longa 100 mg/kg (CL-100 treated group) respectively for one month. On the 31st day, rats of the control I/R and Cl treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. I/R resulted in significant cardiac necrosis, depression in left ventricular function, decline in antioxidant status and elevation in lipid perodixation in the control I/R group as compared to sham control. Myocardial infarction produced after I/R was significantly reduced in the Cl treated group. Cl treatment resulted in restoration of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I/R. Furthermore, I/R-induced lipid peroxidation was significantly inhibited by Cl treatment. The beneficial cardioprotective effects also translated into the functional recovery of the heart. Cardioprotective effect of Cl likely results from the suppression of oxidative stress and correlates with the improved ventricular function. Histopathological examination further confirmed the protective effects of Cl on the heart.

  Mining MEDLINE for implicit links between dietary substances and diseases.:Bioinformatics. 2004 Aug 4;20 Suppl 1:i290-6.Srinivasan P, Libbus B.School of Library and Information Science, University of Iowa, Iowa City, IA 52242, USA. padmini-srinivasan@uiowa.edu

 MOTIVATION: Text mining systems aim at knowledge discovery from text collections. This work presents our text mining algorithm and demonstrates its use to uncover information that could form the basis of new hypotheses. In particular, we use it to discover novel uses for Curcuma longa, a dietary substance, which is highly regarded for its therapeutic properties in Asia. RESULTS: Several disease were identified that offer novel research contexts for curcumin. We analyze select suggestions, such as retinal diseases, Crohn's disease and disorders related to the spinal cord. Our analysis suggests that there is strong evidence in favor of a beneficial role for curcumin in these diseases. The evidence is based on curcumin's influence on several genes, such as COX-2, TNF-alpha, JNK, p38 MAPK and TGF-beta. This research suggests that our discovery algorithm may be used to suggest novel uses for dietary and pharmacological substances. More generally, our text mining algorithm may be used to uncover information that potentially sheds new light on a given topic of interest. AVAILABILITY: Contact authors.


  Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers.:J Assoc Physicians India. 2003 Nov;51:1055-60.Joshi J, Ghaisas S, Vaidya A, Vaidya R, Kamat DV, Bhagwat AN, Bhide S.Bhavan's Swami Prakashananda Ayurveda Research Centre, 13th NS Road, Juhu, Mumbai 400 049.

 OBJECTIVE: Turmeric extract and turmeric oil have shown chemoprotective effect against chemically-induced malignancies in experimental animals. They can reverse precancerous changes in oral submucous fibrosis in humans. The use of turmeric or Curcuma longa Linn as a spice and household remedy has been known to be safe for centuries. In view of the long term administration required for cancer prevention a Phase I clinical trial of turmeric oil (TO) was designed to study the safety and tolerance of TO in volunteers for a period of 3 months. MATERIAL AND METHODS: Nine healthy volunteers between 20 and 33 years of age were tested for haemoglobin, blood counts, liver and kidney functions, bleeding and clotting time and serum electrolytes initially and at 1 and 3 months of treatment. They were administered 0.6 ml of TO three times a day for 1 month and 1 ml in 3 divided doses for 2 months. The acute tolerability study on Day 1 was conducted in a Clinical Pharmacology daycare Unit. Blood pressure and pulse were recorded frequently on Day 1 and at 24, 48, 72 and 96 hours and fortnightly till 12 weeks. Volunteers were daily supervised for TO intake as well as for any side effects throughout the study period. RESULTS: Nine volunteers were enrolled for the study. One discontinued on 3rd day for allergic skin rashes which, on discontinuation of TO, gradually disappeared by two weeks. Another discontinued on 7th day for intercurrent fever requiring antibiotic treatment. Seven volunteers completed the study. There was no effect of TO, in two doses, on pulse and blood pressure and no side effects in acute tolerability study on Day 1. There was no effect of TO intake on weight, blood pressure, symptoms and signs upto 12 weeks. There was no clinical, haematological, renal or hepatic-toxicity of TO at 1 month and 3 months. Serum lipids did not show significant change except in one volunteer (reversible). CONCLUSIONS: In view of the potential for reversing oral submucous fibrosis, a precancerous condition for oral cancer, TO, can be recommended directly for a Phase II trial in patients.

  Antioxidant effect of curcumin in selenium induced cataract of Wistar rats.:Indian J Exp Biol. 2004 Jun;42(6):601-3.Padmaja S, Raju TN.Physiology Division, Department of Zoology, University College of Science, Osmania University, Hyderabad 500 007, India.

 Wistar rat pups treated with curcumin, a natural constituent of Curcuma longa before being administered with selenium showed no opacities in the lens. The lipid peroxidation, xanthine oxidase enzyme levels in the lenses of curcumin and selenium co-treated animals were significantly less when compared to selenium treated animals. The superoxidase dismutase and catalase enzyme activities of curcumin and selenium co-treated animal lenses showed an enhancement. Curcumin co-treatment seems to prevent oxidative damage and found to delay the development of cataract.

  Induction of apoptosis by ar-turmerone on various cell lines.:Int J Mol Med. 2004 Aug;14(2):253-6.Ji M, Choi J, Lee J, Lee Y.School of Life Science, Shandong University, Jinan 250100, China.

 This study investigated the cytotoxic effect of ar-turmerone isolated from turmeric (Curcuma longa L) on the K562, L1210, U937 and RBL-2H3 cell lines by the MTT assay. Ar-turmerone exhibited potent cytotoxicity on these cancer cell lines. The IC50 values of ar-turmerone on these cell lines were 20-50 microg/ml. They showed an increased inhibition ratio on cell viability according to the drug concentration < or = 80 microg/ml in the cell lines tested. The DNA fragmentation that is a characteristic of apoptosis due to ar-turmerone occurred in a concentration- and time-dependent manner in the K562, L1210, U937 and RBL-2H3 cancer cell lines. These results suggest that ar-turmerone can induce the apoptotic activity in the K562, L1210, U937 and RBL-2H3 cells.

  In vitro and in vivo anti-tumoral effect of curcumin against melanoma cells.:Int J Cancer. 2004 Sep 1;111(3):381-7.Odot J, Albert P, Carlier A, Tarpin M, Devy J, Madoulet C.Laboratoire de Biologie Cellulaire et Mol¨¦culaire, EA 3306 U.F.R Sciences, Reims, France.

 Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is known to be an anti-oxidant and an anti-inflammatory agent. It has been demonstrated recently to possess anti-angiogenic effects and pro-apoptotic activities against Ehrlich ascites tumor cells. In the current study, curcumin was found to be cytotoxic in vitro for B16-R melanoma cells resistant to doxorubicin either cultivated as monolayers or grown in three-dimensional (3-D) cultures (spheroids). We have demonstrated that the cytotoxic effect observed in the 2 culture types can be related to the induction of programmed cell death. In our in vivo studies, we examined the effectiveness of a prophylactic immune preparation of soluble proteins from B16-R cells, or a treatment with curcumin as soon as tumoral appearance, alone or in combination, on the murine melanoma B16-R. The combination treatment resulted in substantial inhibition of growth of B16-R melanoma, whereas each treatment by itself showed little effect. Moreover, animals receiving the combination therapy exhibited an enhancement of their humoral anti-soluble B16-R protein immune response and a significant increase in their median survival time (> 82.8% vs. 48.6% and 45.7% respectively for the immunized group and the curcumin-treated group). Our study shows that curcumin may provide a valuable tool for the development of a therapeutic combination against the melanoma.

  Inhibitory activity of diarylheptanoids on farnesyl protein transferase.:Nat Prod Res. 2004 Aug;18(4):295-9.Kang HM, Son KH, Yang DC, Han DC, Kim JH, Baek NI, Kwon BM.Korea Research Institute of Bioscience and Biotechnology, 52 Uendong, Yusung, Taejon 305-600, Republic of Korea.

 Diarylheptanoids [curcumin (1), demethoxycurcumin (2), bisdemethoxycurcumin (3), bisdimethoxymethylcurcumin (4), and 1,2-dihydrobis(de-O-methyl)curcumin (5)] were isolated from the methanolic extract of Curcuma longa L. and a new cyclic diarylheptanoid (6) and a known Compound 7 were isolated from fruits of Alnus japonica Steud. Diarylheptanoids (1-3) inhibited farnesyl protein transferase (FPTase) with an IC50 of 29-50 microM. The other compounds very mildly inhibited FPTase, therefore, the inhibitory activity on FPTase very much depends on the structure of diarylheptanoids.


  Quantitative determination of curcuminoids in Curcuma rhizomes and rapid differentiation of Curcuma domestica Val. and Curcuma xanthorrhiza Roxb. by capillary electrophoresis.:Phytochem Anal. 2004 May-Jun;15(3):152-8.Lechtenberg M, Quandt B, Nahrstedt A.Institute of Pharmaceutical Biology and Phytochemistry, Hittorfstrasse 56, D-48149 M¨¹nster, Germany.

 The three major curcuminoids, curcumin, demethoxycurcumin and bis-demethoxycurcumin, from Curcuma domestica Val. (Curcuma longa L.) and Curcuma xanthorrhiza Roxb. (Zingiberaceae) were fully separated and quantified in less than 5 min using a capillary zone electrophoresis method with standard fused-silica capillaries and photodiode array detection. An electrolyte solution of 20 mM phosphate, 50 mM sodium hydroxide and 14 mM beta-cyclodextrin was found to be appropriate. Quantification was performed with 3,4-dimethoxy-trans-cinnamic acid as internal standard, and the limit of detection was 0.01 mg/mL. Extraction, stabilisation during sample storage and quantification procedures were optimised and carried out with drugs and commercial curry powder from different provenances. The results were compared with the photometric method of the monograph Curcumae xanthorrhizae rhizoma of the European Pharmacopoeia.

  Curcumin blocks multiple sites of the TGF-beta signaling cascade in renal cells.:Kidney Int. 2004 Jul;66(1):112-20.Gaedeke J, Noble NA, Border WA.Fibrosis Research Laboratory, Division of Nephrology, University of Utah, Salt Lake City, Utah, USA.

 BACKGROUND: Over-expression of transforming growth factor-beta (TGF-beta) contributes greatly to fibrotic kidney disease. The activator protein-1 (AP-1) inhibitor curcumin, a polyphenolic compound derived from Curcuma longa, has been shown to reduce collagen accumulation in experimental pulmonary fibrosis. Here, we investigate curcumin's ability to modulate TGF-beta's profibrotic actions in vitro. METHODS: NRK49F rat renal fibroblasts were stimulated with TGF-beta (5 ng/mL), and the effects of curcumin on TGF-beta-regulated genes, TGF-beta receptors, and phosphorylated SMAD isoforms were analyzed by Northern blotting, enzyme-linked immunosorbent assay (ELISA), and Western blotting. The effects of c-jun depletion on TGF-beta-regulated gene and protein expression were analyzed with RNAi. RESULTS: When applied 30 minutes before TGF-beta, curcumin dose dependently and dramatically reduced TGF-beta-induced increases in plasminogen activator inhibitor-1 (PAI-1), TGF-beta1, fibronectin (FN) and collagen I (Col I) mRNA, and in PAI-1 and fibronectin protein. Prolonged curcumin treatment (>6 h) significantly reduced TGF-beta receptor type II levels and SMAD2/3 phosphorylation in response to added TGF-beta. Depletion of cellular c-jun levels with a RNAi method mimicked the effects of curcumin on expression of TGF-beta1, FN, and Col I, but not PAI-1. CONCLUSION: Curcumin blocks TGF-beta's profibrotic actions on renal fibroblasts through down-regulation of TbetaRII, and through partial inhibition of c-jun activity. These in vitro data suggest that curcumin might be an effective antifibrotic drug in the treatment of chronic kidney disease.

  Role of curcumin, a naturally occurring phenolic compound of turmeric in accelerating the repair of excision wound, in mice whole-body exposed to various doses of gamma-radiation.:J Surg Res. 2004 Jul;120(1):127-38.Jagetia GC, Rajanikant GK.Department of Radiobiology, Kasturba Medical College, Manipal, India. gc.jagetia@kmc.manipal.edu

 The healing of irradiated wounds has always been a central consideration in medical practice because radiation disrupts normal response to injury, leading to a protracted recovery period. The quest for clinically effective wound healing agents is important in the medical management of irradiated wounds. Therefore, the present study was conceptualized to investigate the effect of curcumin (natural yellow, diferuloylmethane), a major yellow pigment and an active component of turmeric on wound healing in mice exposed to whole-body gamma-radiation. A full-thickness wound was created on the dorsum of mice whole-body irradiated to 2, 4, 6, or 8 Gy. The progression of wound contraction was monitored periodically by capturing video images of the wound. The collagen, hexosamine, DNA, nitric oxide, and histological profiles were evaluated at various postirradiation days in mice treated and not treated with curcumin before exposure to 0 or 6 Gy. The whole-body exposure resulted in a dose-dependent delay in wound contraction and prolongation of wound healing time. Irradiation caused a significant reduction in collagen, hexosamine, DNA, and nitric oxide synthesis. Pretreatment with curcumin significantly enhanced the rate of wound contraction, decreased mean wound healing time, increased synthesis of collagen, hexosamine, DNA, and nitric oxide and improved fibroblast and vascular densities. This study demonstrates that curcumin pretreatment has a conducive effect on the irradiated wound and could be a substantial therapeutic strategy in initiating and supporting the cascade of tissue repair processes in irradiated wounds.

  Role of selected Indian plants in management of type 2 diabetes: a review.:J Altern Complement Med. 2004 Apr;10(2):369-78. Review.Saxena A, Vikram NK.Department of Medicine, All India Institute of Medical Sciences, New Delhi, India. abhasaxena2000@yahoo.com

 Type 2 diabetes has become a global epidemic. Modern medicines, despite offering a variety of effective treatment options, can have several adverse effects. Ayurveda, a science that uses herbal medicines extensively, originated in India. Of considerable interest is the adoption of Ayurveda by the mainstream medical system in some European countries (e.g., Hungary), emphasizing this modality is increasing worldwide recognition. From ancient times, some of these herbal preparations have been used in the treatment of diabetes. This paper reviews the accumulated literature for 10 Indian herbs that have antidiabetic activity and that have been scientifically tested. Few of these herbs, such as Momordica charantia, Pterocarpus marsupium, and Trigonella foenum greacum, have been reported to be beneficial for treating type 2 diabetes. Mechanisms such as the stimulating or regenerating effect on beta cells or extrapancreatic effects are proposed for the hypoglycemic action of these herbs.

  Growth-inhibitory effects of curcumin on ovary cancer cells and its mechanisms.:J Huazhong Univ Sci Technolog Med Sci. 2004;24(1):55-8.Zheng L, Tong Q, Wu C.Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022.

 To study the growth-inhibitory effects of curcumin on human ovary cancer A2780 cells in vitro and its molecular mechanisms, the growth inhibition rates of A2780 cancer cells, after being treated with 10 micromol/L-50 micromol/L curcumin for 6-24 h, were examined by MTT method. The morphological changes of cancer cells were observed under inversion microscopy. Cellular apoptotic rates were determined by using TUNEL. The protein expression levels of bcl-2, p53 and MDM2 in cancer cells were examined by SP immunohistochemistry. After being treated by various concentrations of curcumin, the growth of cancer cells was inhibited significantly. Some cancer cells presented characteristic morphological changes of apoptosis. The rates of apoptosis were 6.41%-28.48% (P<0.01). The expression of bcl-2 and p53 was decreased, which depended on the action time (P<0.01). There were no obvious changes in MDM2 expression. It was concluded that curcumin could significantly inhibit the growth of ovary cancer cells. The induction of apoptosis by down-regulating the expression of bcl-2 and p53 was probably one of its molecular mechanisms.


  Antimutagenicity of herbal detoxification formula Smoke Shield against environmental mutagens.:J Exp Clin Cancer Res. 2004 Mar;23(1):61-8.Kuttan R, Kuttan G, Joseph S, Ajith TA, Mohan M, Srimal RC.Amala Cancer Research Centre, Amala Nagar, Kerala, India.

 Smoke Shield is a formulation designed to reduce smoke related mutagenicity and toxicity in the population. Smoke Shield contains a dual extract of turmeric (Curcuma longa) obtained by supercritical CO2 gas extraction and post-supercritical hydroethanolic extraction together with extracts of green tea and other spices, whose presence synergistically increases the activity of turmeric. In the present study we have shown its antimutagenic activity to various environmental mutagens in vitro and in vivo. Smoke Shield was found to produce significant inhibition of mutagenicity to Salmonella typhimurium induced by sodium azide and 4-nitro-0-phenylenediamine (NPD) at a concentration of 2 mg/plate while inhibition to N-methyl-N-nitro N'nitrosoguanidine was less significant. Inhibition was also found to depend upon the strain which was used. Smoke Shield was found to be more effective against mutagens needing metabolic activation such as 2-Acetamidofluorene (2-AAF) and benzo[a]pyrene. Smoke Shield was also found to significantly inhibit the mutagenicity induced by tobacco extract to Salmonella typhimurium TA102. Smoke Shield was also found to inhibit the urinary mutagenicity of rats treated with the benzo[a]pyrene and tobacco extract. Moreover, Smoke Shield administration was found to inhibit the urinary mutagenicity in smokers. These results indicate that Smoke Shield could inhibit mutagenic response in vitro and in vivo produced by several kinds of mutagens present in our atmosphere.

  Induction of apoptosis in human lung cancer cells by curcumin.:Cancer Lett. 2004 May 28;208(2):163-70.Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP, Carrier E.Department of Medicine, Pediatrics and Family and Preventive Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0062, USA.

 Curcumin, a phenolic compound from the rhizome of the plant Curcuma longa has anti-inflammatory, antioxidant and anti-cancer activities. Although the precise mode of action of this compound is not yet elucidated, studies have shown that chemo-preventive action of curcumin might be due to its ability to induce apoptosis and to arrest cell cycle. This study investigated the cellular and molecular changes induced by curcumin leading to the induction of apoptosis in human lung cancer cell lines-A549 and H1299. A549 is p53 proficient and H1299 is p53 null mutant. The lung cancer cells were treated with curcumin (0-160 microM) for 12-72 h. Curcumin inhibited the growth of both the cell lines in a concentration dependent manner. Growth inhibition of H1299 cell lines was both time and concentration dependent. Curcumin induced apoptosis in both the lung cancer cell lines. A decrease in expression of p53, bcl-2, and bcl-X(L) was observed after 12 h exposure of 40 microM curcumin. Bak and Caspase genes remained unchanged up to 60 microM curcumin but showed decrease in expression levels at 80-160 microM. The data also suggest a p53 independent induction of apoptosis in lung cancer cells.

  Spice phenolics inhibit human PMNL 5-lipoxygenase.:Prostaglandins Leukot Essent Fatty Acids. 2004 Jun;70(6):521-8.Prasad NS, Raghavendra R, Lokesh BR, Naidu KA.Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570 013, India.

 A wide variety of phenolic compounds and flavonoids present in spices possess potent antioxidant, antimutagenic and anticarcinogenic activities. We examined whether 5-lipoxygenase (5-LO), the key enzyme involved in biosynthesis of leukotrienes is a possible target for the spices. Effect of aqueous extracts of turmeric, cloves, pepper, chili, cinnamon, onion and also their respective active principles viz., curcumin, eugenol, piperine, capsaicin, cinnamaldehyde, quercetin, and allyl sulfide were tested on human PMNL 5-LO activity by spectrophotomeric and HPLC methods. The formation of 5-LO product 5-HETE was significantly inhibited in a concentration-dependent manner with IC(50) values of 0.122-1.44 mg for aqueous extracts of spices and 25-83 microM for active principles, respectively. The order of inhibitory activity was of quercetin>eugenol>curcumin>cinnamaldehyde>piperine>capsaicin>allyl sulfide. Quercetin, eugenol and curcumin with one or more phenolic ring and methoxy groups in their structure showed high inhibitory effect, while the non-phenolic spice principle allyl sulfide showed least inhibitory effect on 5-LO. The inhibitory effect of quercetin, curcumin and eugenol was similar to that of synthetic 5-LO inhibitors-phenidone and NDGA. Moreover, the inhibitory potency of aqueous extracts of spice correlated with the active principles of their respective spices. The synergistic or antagonistic effect of mixtures of spice active principles and spice extracts were investigated and all the combinations of spice active principles/extracts exerted synergistic effect in inhibiting 5-LO activity. These findings clearly suggest that phenolic compounds present in spices might have physiological role in modulating 5-LO pathway.

  Protective effects of a mixture of dietary agents against 7,12-dimethylbenz[a]anthracene-induced genotoxicity and oxidative stress in mice.:J Med Food. 2004 Spring;7(1):55-60. Chandra Mohan KV, Abraham SK, Nagini S.Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.

 We investigated the effects of pretreatment with tomato, garlic, and turmeric, alone and in combination, against 7,12-dimethylbenz[a]anthracene (DMBA)-induced genetic damage and oxidative stress in male Swiss mice. Measurement of the incidence of bone marrow micronuclei as well as the extent of lipid peroxidation and the status of the antioxidants reduced glutathione, glutathione peroxidase, and glutathione-S-transferase in the liver and erythrocytes were used as biomarkers of chemoprotection. In DMBA-treated animals, increased frequency of bone marrow micronuclei was accompanied by enhanced lipid peroxidation and antioxidant depletion. Pretreatment with tomato, garlic, and turmeric alone and a combination of these agents significantly reduced the frequencies of DMBA-induced bone marrow micronuclei as well as the extent of lipid peroxidation. These changes may be mediated by the antioxidant-enhancing effects of the dietary agents. The results of the present study suggest that a diet containing even low levels of different naturally occurring compounds is effective in exerting antigenotoxic effects by inhibiting DMBA-induced oxidative stress.

  Biological properties of curcumin-cellular and molecular mechanisms of action.:Crit Rev Food Sci Nutr. 2004;44(2):97-111. Review.Joe B, Vijaykumar M, Lokesh BR.Department of Physiology and Molecular Medicine, Medical College of Ohio, Block Health Science Building, 3035 Arlington Avenue, Toledo, OH 43614-5804, USA. bjoe@mco.edu

 Curcuminoids, a group of phenolic compounds isolated from the roots of Curcuma longa (Zingiberaceae), exhibit a variety of beneficial effects on health and on events that help in preventing certain diseases. A vast majority of these studies were carried out with curcumin (diferuloyl methane), which is a major curcuminoid. The most detailed studies using curcumin include anti-inflammatory, antioxidant, anticarcinogenic, antiviral, and antiinfectious activities. In addition, the wound healing and detoxifying properties of curcumin have also received considerable attention. As a result of extensive research on the therapeutic properties of curcumin, some understanding on the cellular, molecular, and biochemical mechanism of action of curcumin is emerging. These findings are summarized in this review.


  Anti-apoptotic effects of curcumin on photosensitized human epidermal carcinoma A431 cells.:J Cell Biochem. 2004 May 1;92(1):200-12.Chan WH, Wu HJ.Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan, Republic of China. whchan@cycu.edu.tw

 Photodynamic treatment (PDT) can elicit a diverse range of cellular responses, including apoptotic cell death. Previously, we showed that PDT stimulates caspase-3 activation and subsequent cleavage and activation of p21-activated kinase 2 (PAK2) in human epidermal carcinoma A431 cells. Curcumin, the yellow pigment of Curcuma longa, is known to have anti-oxidant and anti-inflammatory properties. In the present study, using Rose Bengal (RB) as the photosensitizer, we investigated the effect of curcumin on PDT-induced apoptotic events in human epidermal carcinoma A431 cells. We report that curcumin prevented PDT-induced JNK activation, mitochondrial release of cytochrome c, caspase-3 activation, and cleavage of PAK2. Using the cell permeable dye DCF-DA as an indicator of reactive oxygen species (ROS) generation, we found that both curcumin and ROS scavengers (i.e., l-histidine, a-tocopherol, mannitol) abolished PDT-stimulated intracellular oxidative stress. Moreover, all these PDT-induced apoptotic changes in cells could be blocked by singlet oxygen scavengers (i.e., l-histidine, a-tocopherol), but were not affected by the hydroxyl radical scavenger mannitol. In addition, we found that SP600125, a JNK-specific inhibitor, reduced PDT-induced JNK activation as well as caspase-3 activation, indicating that JNK activity is required for PDT-induced caspase activation. Collectively, these results demonstrate that singlet oxygen triggers JNK activation, cytochrome c release, caspase activation and subsequent apoptotic biochemical changes during PDT and show that curcumin is a potent inhibitor for this process.

  Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids.:BMC Cancer. 2004 Apr 17;4:13.Limtrakul P, Anuchapreeda S, Buddhasukh D.Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. plimtrak@mail.med.cmu.ac.th

 BACKGROUND: Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in patient's tumor cells resulting from enhanced drug efflux. It is related to the overexpression of a membrane protein, P-glycoprotein (Pgp-170), thereby reducing drug cytotoxicity. A variety of studies have tried to find MDR modulators which increase drug accumulation in cancer cells. METHODS: In this study, natural curcuminoids, pure curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from turmeric (Curcuma longa Linn), were compared for their potential ability to modulate the human MDR-1 gene expression in multidrug resistant human cervical carcinoma cell line, KB-V1 by Western blot analysis and RT-PCR. RESULTS: Western blot analysis and RT-PCR showed that all the three curcuminoids inhibited MDR-1 gene expression, and bisdemethoxycurcumin produced maximum effect. In additional studies we found that commercial grade curcuminoid (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemthoxycurcumin) decreased MDR-1 gene expression in a dose dependent manner and had about the same potent inhibitory effect on MDR-1 gene expression as our natural curcuminoid mixtures. CONCLUSION: These results indicate that bisdemethoxycurcumin is the most active of the curcuminoids present in turmeric for modulation of MDR-1 gene. Treatment of drug resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decreased MDR-1 gene product, a P-glycoprotein, on the cell plasma membrane. Although many drugs that prevent the P-glycoprotein function have been reported, this report describes the inhibition of MDR-1 expression by a phytochemical. The modulation of MDR-1 expression may be an attractive target for new chemosensitizing agents.

  Contraceptive effect of Curcuma longa (L.) in male albino rat.:Asian J Androl. 2004 Mar;6(1):71-4.Ashok P, Meenakshi B.Department of Zoology, JNV University, Jodhpur (Raj.) 342 005, India. purohit1411@yahoo.com

 AIM: To study the contraceptive effect of the crude extracts of Curcuma longa in male albino rats. METHODS: Rats were fed orally with Curcuma longa aqueous and 70% alcoholic extract for 60 days (500 mg x kg(-1) x day(-1)). RESULTS: A reduction in sperm motility and density was observed in both the treated groups. CONCLUSION: Curcuma longa may have affected the androgen synthesis either by inhibiting the Leydig cell function or the hypothalamus pituitary axis and as a result, spermatogenesis is arrested.

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  Scientific References:

  1.Research Update:Curcumae Longae.Curcuma longa.