Research Update of Gotu Kola Centella asiatica,the Goddess of Supreme Wisdom.

  seminal trace...Gotu Kola.Madecassic acid,Asiaticoside.Total Triterpenes 10%20%40%70%HPLCAsiaticoside 40%HPLC. TECA 92~95%HPLC; Madecassic Acid 93%HPLCGotu Kola Extracts in Series:Total Triterpenes,Centella Selected Triterpenes.TECA,CAS No.:84696-21-9,Asiaticoside,CAS.NO:16830-15-2;M.F.C48H78O18,Asiatic acid,CAS.NO:464-92-6;M.F.:C30H48O5,Madecassic acid,CAS.NO:18449-41-7;M.F.C30H48O6...

 


   Phytochemical info of Gotu Kola Extract.Centella asiatica.:

 Product Name:
 Synonym:
 Definition:Gotu Kola Extract.Centella asiatica are majorly composed of .
 Chemical information disclosed as following table:


   Research Update of Gotu Kola Centella asiatica.:


  A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects..:

 J Clin Psychopharmacol. 2000; 20(6):680-4 (ISSN: 0271-0749).Bradwejn J; Zhou Y; Koszycki D; Shlik J.Royal Ottawa Hospital and the Department of Psychiatry, University of Ottawa, Ontario, Canada. jbradwej@rohcg.on.ca
 Investigations of the pharmacologic profile of medicinal plants have revealed that a number of plants with purported anxiolytic activity bind to cholecystokinin (CCK) receptors. This finding is intriguing in view of the proposed involvement of CCK in the pathophysiology of fear and anxiety. This double-blind, placebo-controlled study was undertaken to evaluate the anxiolytic activity of Gotu Kola (Centella asiatica) in healthy subjects. Gotu Kola has been used for centuries in Ayurvedic and traditional Chinese medicine to alleviate symptoms of depression and anxiety. Recent studies in the rat have shown that long-term pretreatment with Gotu Kola decreases locomotor activity, enhances elevated-plus maze performance, and attenuates the acoustic startle response (ASR). In this study, the authors evaluated the effects of Gotu Kola on the ASR in humans. Subjects were randomly assigned to receive either a single 12-g orally administered dose of Gotu Kola (N = 20) or placebo (N = 20). The results revealed that compared with placebo, Gotu Kola significantly attenuated the peak ASR amplitude 30 and 60 minutes after treatment. Gotu Kola had no significant effect on self-rated mood, heart rate, or blood pressure. These preliminary findings suggest that Gotu Kola has anxiolytic activity in humans as revealed by the ASR. It remains to be seen whether this herb has therapeutic efficacy in the treatment of anxiety syndromes.

  Medicinal foodstuffs. XXVII. Saponin constituents of gotu kola (2): structures of new ursane- and oleanane-type triterpene oligoglycosides,centellasaponins B, C, and D, from Centella asiatica cultivated in Sri Lank.:

 Ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D, were isolated from the aerial parts of Centella asiatica (L.) Urban cultivated in Sri Lanka together with madecassoside, asiaticoside, asiaticoside B, and sceffoleoside A. The chemical structures of centellasaponins B, C, and D were determined on the basis of chemical and physicochemical evidence to be madecassic acid 28-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, madasiatic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, and 3beta,6beta,23-trihydroxyolean-12-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, respectively.

  From medical herbalism to phytotherapy in dermatology: back to the future.:

 Dermatol Ther. 2003; 16(2):106-13 (ISSN: 1396-0296).Dattner AM.Integrative Medicine and Dermatology, New Rochelle, New York 10805, USA. drdattner@yahoo.com
 Plant-based therapeutic preparations are cyclically returning to complement dermatologic therapy. They serve as therapeutic alternatives, safer choices, or in some cases, as the only effective treatment. Folk medicine tradition provides different indicators for use than the medical disease model.
 Advantages of multiple synergistic components of crude extracts are discussed, as well as herbs already used in dermatology. Bitter digestive stimulants are used for vitiligo. Bioflavinoids from buckwheat and horse chestnut are used for varicose veins, and silymarin is used for liver protection. Gotu kola and sarsaparilla are used for inflammatory skin conditions. Oregon grape root has synergistic antibacterial, anti-inflammatory, and bile-stimulating properties which make the crude extract useful in acne. Philosophical differences in herbology compared to medicine exist in the application of science toward improving elimination and strengthening the host as opposed to destroying the vector or manifestation of the disease.

  Efficiency of includes of bioactive substances in diet of patient with hepatic encephalopathy.:Vopr Pitan. 2006; 75(2):40-4 (ISSN: 0042-8833).Kaziulin AN; Petukhov AB; Kucheriavy?? IuA

 We includes 66 patients with liver cirrhosis of Child-Pugh B class with hepatic encephalopathy of 0 to 2nd stages in randomized interventional study. 36 patients received standard treatment and 30 patients received standard treatment + bioactive substances in formula CognoBlend in capsules (2 capsules twice a day) in course of 5 weeks. Formula includes extracts of plants: Bacopa monneria, Gingko biloba, Cat's Claw, Gotu Kola, Rosemary. In group combined treatment was significant improvement of clinical signs, psychometric tests, electroencephalography and serum biochemistry than in group with standard therapy, on term of 2 to 5 weeks.

  Hepatotoxicity associated with the ingestion of Centella asiatica.:Rev Esp Enferm Dig. 2005; 97(2):115-24 (ISSN: 1130-0108)Jorge OA; Jorge AD.Gastroenterology Department, Hospital Espa??ol, Mendoza, Argentina. oliverjorge@lanet.com.ar

 BACKGROUND: Hepatotoxicity due to herbal remedies is being increasingly recognized. Centella asiatica (Centella asiatica Linn Urban) is commercialized for multiple conditions. Its active principles are pentacyclic triterpenic saponosides (asiaticoside, madecassoside).
 CLINICAL CASE STUDIES: We present three women (61, 52 and 49 years old) who developed jaundice after taking Centella asiatica for 30, 20 and 60 days. Respective laboratory tests: ALT: 1193, 1694 and 324 U/L; ALP: 503, 472 and 484 U/L; bilirubin: 4.23, 19.89 and 3.9 mg/dl. The first patient also had ASMA 1/160 and AMA 1/320. Respective pathological diagnoses: granulomatous hepatitis with marked necrosis and apoptosis; chronic hepatitis with cirrhotic transformation and intense necroinflammatory activity, and granulomatous hepatitis. All patients improved with Centella asiatica discontinuation, and ursodeoxycholic acid 10 mg/kg/day. The first patient took Centella asiatica again, with recurrence of the damage. The second one had taken this herb a year before.
 CONCLUSIONS: Many plants synthesize hepatotoxic compounds. Germander, Skullcap and Glycyrrhizin contain di- or triterpenic active principles, which can produce hepatic injury by promoting apoptosis and altering cell membranes. We hypothesize that these mechanisms may have resulted in injuries associated with Centella asiatica. The presence of autoantibodies and granulomas also favors an immune-mediated mechanism. Ursodeoxycholic acid has anti-apoptotic properties, but we cannot rule out that Centella asiatica discontinuation alone may have resulted in patient improvement.


  Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro.:

 J Pharm Pharmacol. 2005; 57(9):1221-9 (ISSN: 0022-3573).Soumyanath A; Zhong YP; Gold SA; Yu X; Koop DR; Bourdette D; Gold BG.Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland OR 97239, USA.
 Axonal regeneration is important for functional recovery following nerve damage. Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth factor (NGF). However, a water extract of Centella was ineffective at 100 microg mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel chromatography, were tested (100 microg mL-1) for neurite elongation in the presence of NGF. Greatest activity was found with a non-polar fraction (GKF4). Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less than GKF4. Thus, Centella contains more than one active component. Asiatic acid (AA), a triterpenoid compound found in Centella ethanolic extract and GKF4, showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to GKF13, further indicating that other active components must be present. Neurite elongation by AA was completely blocked by the extracellular-signal-regulated kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily) demonstrated more rapid functional recovery and increased axonal regeneration (larger calibre axons and greater numbers of myelinated axons) compared with controls, indicating that the axons grew at a faster rate. Taken together, our findings indicate that components in Centella ethanolic extract may be useful for accelerating repair of damaged neurons.

  Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids.:

 Planta Med. 2003; 69(8):725-32 (ISSN: 0032-0943).Coldren CD; Hashim P; Ali JM; Oh SK; Sinskey AJ; Rha C.Malaysia-MIT Biotechnology Partnership Program, Cambridge, MA, USA.
 The molecular pathways underlying the diverse biological activity of the triterpeniod compounds isolated from the tropical medicinal plant Centella asiatica were studied with gene microarrays and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) to quantify the expression of 1053 human genes in human fibroblasts. Fibroblast cells grown in culture were used as a model system to evaluate the stimulation of wound healing by titrated extract from Centella asiatica (TECA) as well as by the four principal triterpenoid components of Centella. TECA treatment effects the expression of genes involved in angiogenesis and the remodeling of extracellular matrix, as well as diverse growth factor genes. The extent of expression change of TNFAIP6, an extracellular hyaluronan binding protein, was found to be largely dose-dependent, to respond most strongly to the free acids asiatic acid and madecassic acid, and to increase in expression over 48 hours of treatment. These results show that Centella triterpenes evoke a gene-expression response consistent with their prevailing medical uses in the treatment of connective tissue disorders such as wound healing and microangiopathy. The identification of genes modulated by these compounds provides the basis for a molecular understanding of Centella's bioactivity, and opportunities for the quantitative correlation of this activity with clinical effectiveness at a molecular level.

  Protective effect of Centella asiatica on antioxidant tissue defense system against adriamycin induced cardiomyopathy in rats.:

 Life Sci. 2004; 76(5):585-97 (ISSN: 0024-3205)Gnanapragasam A; Ebenezar KK; Sathish V; Govindaraju P; Devaki T.Department of Biochemistry, University of Madras, Guindy Campus, Chennai- 600 025, Tamilnadu, India.
 Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin. In this study the cardio protective effect of Centella asiatica on myocardial marker enzymes and antioxidant enzymes in adriamycin induced cardiomyopathy was investigated in rats. The rats administered with adriamycin (2.5 mg/kg body wt, i.p) caused myocardial damage that was manifested by the elevation of serum marker (LDH, CPK, GOT and GPT) enzymes and showed significant changes in the antioxidant enzymes (SOD, CAT, GPx, GST). Pre-co-treatment with Centella asiatica(200 mg/kg of body wt/oral) extract significantly prevented these alterations and restored the enzyme activities to near normal levels. These findings demonstrate the cardio protective effect of Centella asiatica on antioxidant tissue defense system during adriamycin induced cardiac damage in rats.

  The effect of methyl jasmonate on triterpene and sterol metabolisms of Centella asiatica, Ruscus aculeatus and Galphimia glauca cultured plants.:

 Phytochemistry. 2006; 67(18):2041-9 (ISSN: 0031-9422).Mangas S; Bonfill M; Osuna L; Moyano E; Tortoriello J; Cusido RM; Pi??ol MT; Palaz??n J.Laboratorio de Fisiolog??a vegetal, Facultad de Farmacia, Universidad de Barcelona, Avda. Diagonal 643, E-08028 Barcelona, Spain.
 Considering that exogenously applied methyl jasmonate can enhance secondary metabolite production in a variety of plant species and that 2,3-oxidosqualene is a common precursor of triterpenes and sterols in plants, we have studied Centella asiatica and Galphimia glauca (both synthesizing triterpenoid secondary compounds) and Ruscus aculeatus (which synthesizes steroidal secondary compounds) for their growth rate and content of free sterols and respective secondary compounds, after culturing with or without 100 microM methyl jasmonate. Our results show that elicited plantlets of G. glauca and to a higher degree C. asiatica (up to 152-times more) increased their content of triterpenoids directly synthesized from 2,3-oxidosqualene (ursane saponins and nor-seco-friedelane galphimines, respectively) at the same time as growth decreased. In contrast, the free sterol content of C. asiatica decreased notably, and remained practically unaltered in G. glauca. However, in the case of R. aculeatus, which synthesizes steroidal saponins (mainly spirostane type) indirectly from 2,3-oxidosqualene after the latter is converted to the plant phytosterol-precursor cycloartenol, while the growth rate and free sterol content clearly decreased, the spirostane saponine content was virtually unchanged (aerial part) or somewhat lower (roots) in presence of the same elicitor concentration. Our results suggest that while methyl jasmonate may be used as an inducer of enzymes involved in the triterpenoid synthesis downstream from 2,3-oxidosqualene in both C. asiatica and G. glauca plantlets, in those of C. asiatica and R. aculeatus it inhibited the enzymes involved in sterol synthesis downstream from cycloartenol.

  Effect of total triterpenes from Centella asiatica on the depression behavior and concentration of amino acid in forced swimming mice.:

 Zhong Yao Cai. 2003; 26(12):870-3 (ISSN: 1001-4454).Chen Y; Han T; Qin L; Rui Y; Zheng H.School of Pharmacy, Second Military Medical University, Shanghai 200433.
 OBJECTIVE: To evaluate the antidepressant activity of total triterpenes from Centella asiatica in forced swimming test. METHODS: Mice were randomly divided into control group, model group and treatment group. The effect of total triterpenes from Centella asiatica on the immobility time in forced swimming mice and concentration of amino acid in mice brain tissue was observed. RESULTS: Imipramine and total triterpenes from Centella asiatica reduced the immobility time and ameliorated the imbalance of amino acid levels. CONCLUSION: The total triterpenes from Centella asiatica had antidepressant activity.


  Modification of gamma ray induced changes in the mouse hepatocytes by Centella asiatica extract: in vivo studies.:

 Phytother Res. 2005; 19(7):605-11 (ISSN: 0951-418X).Sharma R; Sharma J.Department of Zoology, University of Rajasthan, Jaipur 302004, India. Radhasharma13@yahoo.com
 Ionizing radiation, besides causing direct damage also generates reactive oxygen species that are capable of inducing damage to various organs. Pretreatment with Centella asiatica 1 h prior to irradiation at a dose rate of 100 mg/kg body weight was found to be effective against radiation induced damage in the liver. The number of normal hepatocytes was higher in the Centella asiatica pretreated group in comparison with the irradiated only group. The number of binucleated cells and abnormal hepatocytes was less in comparison with the animals irradiated without Centella asiatica pretreatment.

  Stimulation of asiaticoside accumulation in the whole plant cultures of Centella asiatica (L.) urban by elicitors.:

 Plant Cell Rep. 2004; 23(5):339-44 (ISSN: 0721-7714).Kim OT; Kim MY; Hong MH; Ahn JC; Hwang B.Department of Biology, Chonnam National University, Gwangju, 500-757, South Korea.
 The effects of a number of different elicitors on asiaticoside production in whole plant cultures of Centella asiatica were studied, including yeast extract, CdCl(2), CuCl(2) and methyl jasmonate (MJ). Only MJ and yeast extract stimulated asiaticoside production--1.53 and 1.41-fold, respectively. Maximum asiaticoside production was achieved following treatment with 0.1 mM MJ (116.8 mg/l). The highest asiaticoside production (342.72 mg/l) was obtained after 36 days of elicitation in cultures treated with 0.1 mM MJ and 0.025 mg/l 1-phenyl-3-(1,2,3-thidiazol-5-yl)urea (TDZ). Interestingly, MJ not only stimulated the production of asiaticoside but also had an important role in the senescence of C. asiatica. Although asiaticoside content did not change when TDZ was added to medium containing an elicitor, TDZ did increase shoot growth of C. asiatica. We discuss the interactive roles of MJ and TDZ in secondary metabolic production and biomass in whole plants of C. asiatica.

  Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers and Centella asiatica in lead poisoned rats..:

 J Pharm Pharmacol. 2006; 58(4):547-59 (ISSN: 0022-3573).Saxena G; Flora SJ.Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior-474 002, India.
 This study was designed to investigate the therapeutic potential of meso 2,3-dimercaptosuccinic acid (DMSA) and one of its monoesters, monoisoamyl DMSA (MiADMSA), individually or when administered in combination with an extract of Centella asiatica against experimental lead intoxication in rats. Biochemical variables indicative of alterations in the central nervous system and haem biosynthesis were investigated to determine the toxicity in male Wistar rats. Thirty five rats were exposed to 0.2% lead acetate for 10 weeks, followed by 10 days of treatment with DMSA and MiADMSA (50 mg kg(-1), i.p., once daily) alone and in combination with C. asiatica (200 mg kg(-1), p.o., once daily). Biochemical variables indicative of oxidative stress and brain biogenic amines, along with lead concentration in blood and brain, were measured. Lead exposure caused a significant depletion of blood and brain delta-aminolevulinic acid dehydratase (ALAD) activity, an important enzyme of the haem biosynthesis pathway, and glutathione (GSH) level. These changes were accompanied by a marked increase in reactive oxygen species (ROS) level, thiobarbituric acid reactive substances (TBARS), delta-aminolevulinic acid synthase (ALAS) and oxidized glutathione (GSSG) activity in blood and brain. Significant depletion of brain noradrenaline (norepinephrine, NE), 5-hydroxytryptamine (5-HT), dopamine (DA) and acetylcholinesterase (AChE) also were observed following lead exposure. Also seen was a significant depletion in brain glutathione peroxidase (GPx), glutathione S-transferase (GST) and monoamine oxidase activity, as well as blood and brain superoxide dismutase (SOD) activity. These biochemical changes were correlated with an increased uptake of lead in blood and brain. Combined administration of MiADMSA and C. asiatica was most effective in reducing these alterations, including biogenic amines, besides reducing body lead burden, compared with individual treatment with MiADMSA. Certain other biochemical variables responded favourably to combination therapy and monotherapy with MiADMSA. Thus, supplementation of C. asiatica during chelation could be recommended for achieving optimum effects of chelation therapy.

  Centella asiatica treatment during postnatal period enhances learning and memory in mice.:

 Physiol Behav. 2005; 86(4):449-57 (ISSN: 0031-9384).Rao SB; Chetana M; Uma Devi P.Department of Radiobiology, Kasturba Medical College,Manipal 576104, India.
 Present investigation was planned to evaluate the nootropic effect of Centella asiatica. Three months old male Swiss albino mice were injected orally with graded doses (200, 500, 700, 1000 mg/kg body weight) of C. asiatica aqueous extract for 15 days to select an effective dose for nootropic studies. Animals were tested in radial arm maze to assess the learning and memory performance. Based on these results, mice were treated orally with 200 mg/kg of C. asiatica for 15 days from day 15 to day 30 post partum (p.p.) and the nootropic effect was evaluated on the 31st day and 6 months p.p. The behavioral (open field, dark/bright arena, hole board and radial arm maze tests), biochemical (acetylcholine esterase activity) and histological studies (dendritic arborization) were carried out. Performance of juvenile and young adult mice was significantly improved in radial arm maze and hole board tests, but locomotor activity did not show any change compared to control. Treatment resulted in increased acetylcholine esterase activity in the hippocampus. Dendritic arborization of hippocampal CA3 neurons was also increased in terms of intersections and branching points, both at one month and 6 months. Results of the present investigation show that treatment during postnatal developmental stage with C. asiatica extract can influence the neuronal morphology and promote the higher brain function of juvenile and young adult mice.

  Inhibitory effects of Centella asiatica on azoxymethane-induced aberrant crypt focus formation and carcinogenesis in the intestines of F344 rats.:

 Food Chem Toxicol. 2004; 42(12):1987-97 (ISSN: 0278-6915)
 Effects of the water extract of Centella asiatica Linn. on formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and intestinal tumorigenesis in male F344 rats were investigated. Treatment with the extract significantly decreased the number of larger ACF (with four or more crypts per focus) in the large intestine in the early stage, while the number of methylated DNA adducts was not decreased compared with that in the AOM-treated group. In the post-initiation stage, the extract significantly decreased the total number of ACF and the number of larger ACF, accompanied by a decrease in the 5-bromo-2'-deoxyuridine-labeling index and an increase in the induction of apoptotic cells in the colonic mucosa. The incidences of neoplasms, the numbers of adenocarcinomas in the small intestines and entire intestines, and sizes of neoplasms in the entire intestines in rats fed C. asiatica extract at a dose of 10 mg/kg were smaller than those in rats given AOM alone (p < 0.05). The extract at a dose of 100 mg/kg significantly reduced the multiplicity of neoplasms in the small intestine (p < 0.05). These results suggest that inhibition of the formation of AOM-induced ACF by C. asiatica extract is associated with modification of cell proliferation and induction of apoptosis in colonic crypts and that the extract has a chemopreventive effect on colon tumorigenesis.


  Inhibitory effects of Centella asiatica water extract and asiaticoside on inducible nitric oxide synthase during gastric ulcer healing in rats.:

 Planta Med. 2004; 70(12):1150-4 (ISSN: 0032-0943).Guo JS; Cheng CL; Koo MW.Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong.
 In this study, the effects of Centella asiatica water extract (CE) and its active constituent, asiaticoside (AC), on the expression and activity of inducible nitric oxide synthase (iNOS) during gastric ulcer healing in rats were investigated. CE was prepared from Centella asiatica dry plant and the concentration of AC in CE was quantitatively determined with the use of high performance liquid chromatography analysis. Different concentrations of CE (0.10 g/kg and 0.25 g/kg) and AC (5 mg/kg and 10 mg/kg) were orally administered to rats with acetic acid-induced gastric ulcers. They were found to reduce the size of the ulcers at days 1, 3 and 7 after ulcer induction in a dose-dependent manner, with a concomitant attenuation of iNOS activity and protein expression at the ulcer tissues. The levels of nitrite and nitrate (NO(X)-), the stable end-products of nitric oxide (NO), in the gastric ulcer tissues were also decreased. N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective inhibitor of iNOS, was found to produce similar but more potent inhibition on iNOS activity at a dose of 0.1 mg/kg. These findings indicate that CE and AC have an anti-inflammatory property that is brought about by inhibition of NO synthesis and thus facilitates ulcer healing.

  Isobolographically additive anticonvulsant activity between Centella asiatica's ethyl acetate fraction and some antiepileptic drugs.:

 J Med Assoc Thai. 2005; 88 Suppl 3:S131-40 (ISSN: 0125-2208).Vattanajun A; Watanabe H; Tantisira MH; Tantisira B.PhD Program of Inter-department of Physiology, Graduate School, Chulalongkorn University, Bangkok, Thailand.
 OBJECTIVE: To investigate interaction between orally given Centella asiatica's ethyl acetate fraction (EACA) and intraperitoneally administered antiepileptic drugs (AEDs), namely, phenytoin, valproate and gabapentin.
 MATERIAL AND METHOD: Isobolographic analysis was used to evaluate the interaction between EACA and AEDs in terms of protection of mice in the pentylenetetrazole test. Rotarod test was used to evaluate neurotoxicity.
 RESULTS: When given alone, the median effective dose of phenytoin, valproate and gabapentin were found to be 13, 104, and 310 mg/kg BW, respectively, whereas the corresponding values in the presence of EACA were 5, 29 and 79 mg/kg BW. Together with isobolographic analysis, the results obtained indicated an additive effect among all combinations tested. In relation to neurotoxicity, combination of gabapentin and EACA demonstrated a broader margin between the effective dose and the neurotoxic dose while the other two combinations did not.
 CONCLUSION: The present finding suggested a potential of Centella asiatica to be developed as an adjunctive medication for epileptic patients.

  Effect of total glucosides of Centella asiatica on antagonizing liver fibrosis induced by dimethylnitrosamine in rats.:

 Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004; 24(8):731-4 (ISSN: 1003-5370).Ming ZJ; Liu SZ; Cao L.Department of Pharmacy, School of Medicine,Suzhou University, Jiangsu (215007). mingzj4451@sina.com
 OBJECTIVE: To investigate the anti-liver fibrosis effect of total glucosides of Centella asiatica (GCA) in experimental rats.
 METHODS: Rat liver fibrosis model was induced by injecting dimethylnitrosamine (DMN) intraperitoneally for 6 weeks. Rats were randomly divided into 6 groups, the normal group, the model group, the positive control group treated by colchicine, and the three GCA groups treated by high, moderate and low dosage of GCA through gastrogavage started simultaneously with the modeling. At the end of the experiment, levels of serum total protein (TP), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) were measured, and the pathology of liver tissue was observed.
 RESULTS: The liver function in the GCA groups was improved, the levels of serum ALT, AST, HA were significantly lower than those in the model group (P < 0.05). Histopathological observation showed that GCA has significant anti-liver fibrosis effect. CONCLUSION: GCA has significant preventive and therapeutic effect on DMN induced liver fibrosis in rats.

  Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts. A preliminary study.:

 J Int Acad Periodontol. 2003; 5(4):106-15 (ISSN: 1466-2094).Sastravaha G; Yotnuengnit P; Booncong P; Sangtherapitikul P.Out-Patient Department, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.
 BACKGROUND: Centella asiatica and Punica granatum are medicinal herbs that have been reported to promote tissue healing and modulate host responses. The purpose of this study was to investigate the effects of the combined extracts from C. asiatica and P. granatum pericarp on periodontal healing following scaling and root planing in adult periodontitis patients.
 METHODS: An innovative herbal medicament was formulated in the form of biodegradable chips for subgingival application. Twenty patients with initial pocket depth 5-8 mm were enrolled into the study. After baseline examination, scaling and root planing of non-target teeth, the target teeth received scaling and root planing followed by subgingival delivery of medicated chips in the test group and unmedicated chips in the placebo group. Probing pocket depth, attachment level, bleeding on probing, gingival index, and plaque index were recorded at baseline, 3 and 6 months.
 RESULTS: The results showed significant improvements of pocket depth and attachment level in the test sites when compared with the placebo sites at 3 months and with the placebo and control sites at 6 months. All treatment sites exhibited a similar trend of decreasing plaque score. However, the test sites seemed to show slightly better percentage of bleeding on probing.
 CONCLUSION: The results indicate that local delivery with C. asiatica and P. granatum extracts plus scaling and root planing significantly reduced the clinical signs of chronic periodontitis.

  Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats.:

 Pharmacol Biochem Behav. 2003; 74(3):579-85 (ISSN: 0091-3057).Gupta YK; Veerendra Kumar MH; Srivastava AK.Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, 110029, New Delhi, India. ykg@hotmail.com
 Cognitive impairment in epileptics may be a consequence of the epileptogenic process as well as antiepileptic medication. Thus, there is a need for drugs, which can suppress epileptogenesis as well as prevent cognitive impairment. In the present study, the effect of aqueous extract of Centella asiatica (CA) (100 and 300 mg/kg), an Indian medicinal plant known to possess antiepileptic, cognitive-enhancing and antioxidant property, was evaluated on the course of kindling development, kindling-induced learning deficit and oxidative stress markers in pentylenetetrazole (PTZ) kindled rats. Male Wistar rats were injected PTZ (30 mg/kg ip) once every alternate day (48+/-2 h) until the development of the kindling. Passive avoidance test and spontaneous locomotor activity were carried out 24 and 48 h after the last administration of PTZ, while the oxidative stress parameters (malondialdehyde [MDA] and glutathione) were carried out in the whole brain upon completion of the behavioral assessment. The administration of CA (300 mg/kg orally) decreased the PTZ-kindled seizures and showed improvement in the learning deficit induced by PTZ kindling as evidenced by decreased seizure score and increased latencies in passive avoidance behavior. However, low dose of the CA (100 mg/kg) showed improvement only in the learning deficit due to the kindling and failed to improve the seizure score. The findings suggest the potential of aqueous extract of CA as adjuvant to antiepileptic drugs with an added advantage of preventing cognitive impairment.


  Structure and potential immunological activity of a pectin from Centella asiatica (L.) Urban.:

 Carbohydr Res. 2003; 338(22):2393-402 (ISSN: 0008-6215).Wang XS; Dong Q; Zuo JP; Fang JN.Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, 555 Zu-Chong-Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
 S3A was a RG-I pectin isolated from Centella asiatica that contained Rha, Ara, Gal, Glc and GalA in molar ratio of 1.0:0.6:1.5:0.2:1.1 and had been found to have a backbone composed mainly of the disaccharide repeat unit, -->4)-alpha-D-GalpA-(1-->2)-alpha-L-Rhap-(1-->. Based on methylation analysis, NaIO4 oxidation, partial acid hydrolysis and lithium-treatment, the structural features were elucidated. Side chains of S3A were predominantly linked to O-4 of 1,2,4-linked alpha-L-Rhap. The side chains are comprised of arabinosyl chains, galactosyl chains, arabinogalactosyl chains and short glucosyl chains. A total of 45% Rhap in the backbone was substituted by side chains. The arabinosyl residues were mostly distributed in the arabinosyl side chains. According to the immunological results of S3A and its degraded derivatives, S3A had no immunological activity, but its derivatives had immuno-stimulating activities to some extent.

  An improved HPLC method for quantitative determination of six triterpenes in Centella asiatica extracts and commercial products.:

 Pharmazie. 2003; 58(6):381-4 (ISSN: 0031-7144).Schaneberg BT; Mikell JR; Bedir E; Khan IA.National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS 38677, USA.
 An improved HPLC qualitative and quantitative method of six triterpenes (asiaticoside, madecassoside, asiatic acid, madecassic acid, terminolic acid, and asiaticoside-B) in Centella asiatica (raw plant material and preparations) is described in this paper. After 50 minutes the six active triterpenes were separated and detected in the methanolic extract at a limit of 0.01 microg/ml. The method uses a Phenomenex Aqua 5mu C18 (200 A) column as the stationary phase, a gradient mobile phase of water (0.1% TFA), acetonitrile (0.1% TFA), and methyl tert-butyl ether (0.1% TFA), and UV detection at 206 nm. The correlation coefficients for the calibration curves and the recovery rates ranged from 0.995 to 0.999 and from 98.39% to 100.02%, respectively. The qualitative and quantitative results are discussed.

  Antiproliferative constituents from Umbelliferae plants VII. Active triterpenes and rosmarinic acid from Centella asiatica.:

 Biol Pharm Bull. 2005; 28(1):173-5 (ISSN: 0918-6158)
 The antiproliferative constituents in the MeOH extract from the aerial parts of Centella asiatica were investigated. Activity-guided fractionation of MeOH extract resulted in the isolation of ursolic acid lactone, ursolic acid, pomolic acid, 2alpha,3alpha-dihydroxyurs-12-en-28-oic acid, 3-epimaslinic acid, asiatic acid, corosolic acid, and rosmarinic acid. Antiproliferative activity of the isolated compounds against human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), and murine melanoma (B16F10) cells was estimated.

  Identification of triterpenoid compounds of Centella asiatica by thin-layer chromatography and mass spectrometry.:

 Biomed Chromatogr. 2006; 20(2):151-3 (ISSN: 0269-3879).Bonfill M; Mangas S; Cusid?? RM; Osuna L; Pi??ol MT; Palaz??n J.Laboratorio de Fisiolog??a vegetal, Facultad de Farmacia, Universidad de Barcelona, Avda. Diagonal 643, E-08028 Barcelona, Spain. mbonfill@ub.edu
 The identification of the four principal triterpenoid components of Centella asiatica has been achieved by TLC on silica gel plates and mass spectrometry, as a modification of the method described in the European Pharmacopoeia (5th edn). A combination of ethyl acetate and methanol as the mobile phase was found to be successful in separating these compounds from the rest of the main components of the extract. The spots were detected with anisaldehyde solution. The separated compounds were confirmed by MALDI -TOF mass spectrometry.

  Anti-oxidant activity of Centella asiatica on lymphoma-bearing mice.:

 Fitoterapia. 2003; 74(5):431-4 (ISSN: 0367-326X).Jayashree G; Kurup Muraleedhara G; Sudarslal S; Jacob VB.Applied Biochemistry Laboratory, School of Biosciences, MG University, PD Hills (PO), Kottayam, Kerala 686560, India. jayashree@mbu.iisc.ernet.in
 Oral treatment with 50 mg X kg(-1) day(-1) of crude methanol extract of Centella asiatica for 14 days significantly increased the anti-oxidant enzymes, like superoxide dismutase (SOD), catalase and glutathione peroxidase (GSHPx), and anti-oxidants like glutathione (GSH) and ascorbic acid decreased in lymphoma-bearing mice.


  Centella asiatica (L.) Leaf Extract Treatment During the Growth Spurt Period Enhances Hippocampal CA3 Neuronal Dendritic Arborization in Rats.:

 Evid Based Complement Alternat Med. 2006; 3(3):349-57 (ISSN: 1741-427X).Mohandas Rao KG; Muddanna Rao S; Gurumadhva Rao S
 Centella asiatica (CeA) is a creeping plant growing in damp places in India and other Asian countries. The leaves of CeA are used for memory enhancement in the Ayurvedic system of medicine, an alternative system of medicine in India. In this study, we have investigated the effect during the rat growth spurt period of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal CA3 neurons, one of the regions of the brain concerned with learning and memory. Neonatal rat pups (7 days old) were fed with 2, 4 or 6 ml kg(-1) body weight of fresh leaf extract of CeA for 2, 4 or 6 weeks. After the treatment period the rats were killed, their brains were removed and the hippocampal neurons were impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were traced using a camera lucida, and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with data for age-matched control rats. The results showed a significant increase in the dendritic length (intersections) and dendritic branching points along the length of both apical and basal dendrites in rats treated with 4 and 6 ml kg(-1) body weight per day of CeA for longer periods of time (i.e. 4 and 6 weeks). We conclude that the constituents/active principles present in CeA fresh leaf extract have a neuronal dendritic growth stimulating property; hence, the extract can be used for enhancing neuronal dendrites in stress and neurodegenerative and memory disorders.

  Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica.:

 Phytomedicine. 2000; 7(5):427-48 (ISSN: 0944-7113).Brinkhaus B; Lindner M; Schuppan D; Hahn EG.Department of Traditional and Complementary Medicine, Medical Department I, Friedrich-Alexander University, Erlangen-Nuremberg, Germany. benno.brinkhaus@med1.uni-erlangen.de
 Centella asiatica is a medicinal plant that has been in use since prehistoric times. Its active constituents include pentacyclic triterpene derivatives. Studies have been conducted in particular to investigate the madecassosides and asiaticosides. In common with most traditional phytotherapeutic agents, Centella asiatica is used in folk medicine to treat a wide range of indications. In contrast to other medicinal plants, however, Centella asiatica has been subjected to quite extensive experimental and clinical investigations. Studies done in accordance with standardized scientific criteria have shown it to have a positive effect in the treatment of venous insufficiency and striae gravidarum. Centella asiatica also appears to be effective in the treatment of wound healing disturbances. At the present time, clinical studies aimed at investigating the sedative, analgesic, antidepressive, antimicrobial, antiviral and immunomodulatory effects that have been demonstrated experimentally, are still lacking. However, the therapeutic potential of this plant in terms of its efficacy and versatility is such that further detailed research would appear worthwhile.

  Evaluation of anxiolytic properties of Gotukola--(Centella asiatica) extracts and asiaticoside in rat behavioral models.:

 Phytomedicine. 2006; 13(9-10):668-76 (ISSN: 0944-7113).Wijeweera P; Arnason JT; Koszycki D; Merali Z.Ottawa-Carleton Institute of Biology,University of Ottawa Institute of Mental Health Research, Royal Ottawa Hospital, Canada.
 The ayurvedic medicinal plant Gotukola (Centella asiatica) was evaluated for its anxiolytic properties. Specifically, this study assessed the effects of: Gotukola plant materials of different genotypic origin; hexane, ethyl acetate and methanol extracts of Gotukola; and asiaticoside, a triterpenic compound isolated from Gotukola. Various paradigms were used to assess the anxiolytic activity, including the elevated plus maze (EPM), open field, social interaction, locomotor activity, punished drinking (Vogel) and novel cage tests. The EPM test revealed that Gotukola, its methanol and ethyl acetate extracts as well as the pure asiaticoside, imparted anxiolytic activity. Furthermore, the asiaticoside did not affect locomotor activity, suggesting these compounds do not have sedative effects in rodents.

  Protection against radiation-induced conditioned taste aversion by Centella asiatica.:

 Physiol Behav. 2001; 73(1-2):19-23 (ISSN: 0031-9384)Shobi V; Goel HC.Radiation Biology Division, Institute of Nuclear Medicine and Allied Sciences, DRDO, Lucknow Marg, New Delhi 110 054, India.
 Radiations are known to cause behavioural perturbations like conditioned taste aversion (CTA), performance decrement, learning, etc., even at very low doses. The manifestation of radiation-induced behavioural degradation has not been understood well and requires further studies. Therefore, the effects of low-dose whole-body 60Co gamma-irradiation in male rats were studied in terms of body weight and CTA learning. For CTA, the consumption of saccharin solution was considered as a parameter. To protect against the adverse effects of radiation, Centella asiatica (aqueous extract) was tested and compared with ondansetron, a standard antiemetic drug. A dose of 2 Gy incurred significant body weight loss [t(9)=9.00, P<.05] and induced CTA in rats [t(26)=9.344, P<.01]. Administration of C. asiatica (100 mg/kg bw ip, 2 Gy, -1 h) rendered significant radioprotection against radiation-induced body weight loss and CTA that became evident on the second postirradiation day [t(7)=0.917, P>>.05; t(7)=4.016, P>.05]. Ondansetron (1 mg/kg bw) elicited higher degree of protection against CTA [t(7)=3.641, P>.05] than C. asiatica [t(7)=7.196, P>.05] on the first postirradiation day, but on the second postirradiation day, both were equally effective [t(7)=3.38, P>.05; t(7)=4.01, P>.05]. In case of C. asiatica-treated animals, however, there was a consistently declining CTA from the second to the fifth postirradiation day whereas in ondansetron-treated animals it was inconsistent. Present investigation suggests that C. asiatica could be useful in preventing radiation-induced behavioural changes during clinical radiotherapy.

  In vitro keratinocyte antiproliferant effect of Centella asiatica extract and triterpenoid saponins.:

 Phytomedicine. 2001; 8(3):230-5 (ISSN: 0944-7113).Sampson JH; Raman A; Karlsen G; Navsaria H; Leigh IM.The Centre for Bioactivity Screening of Natural Products, King's College London, UK.
 Psoriasis is a hyperproliferative skin disorder estimated to be present in 1-3% of most populations. Conventional therapy using corticosteroids, Vitamin D analogs and cytotoxic agents eg psoralens is associated with low success rate and many side effects. Traditional plant remedies may provide leads for new treatments. A rapid-throughput, in vitro bioassay has been utilised to examine plants for inhibitory effects on the growth of SVK-14 keratinocytes. Centella asiatica, a reputed anti-psoriatic herb, has been compared against the psoralen-containing seeds of Psoralea corylifolia and the synthetic anti-psoriatic agent dithranol (anthralin). Aqueous extracts of Psoralea corylifolia and Centella asiatica inhibited keratinocyte replication with IC50 values of 18.4 +/- 0.6 microg/ml and 209.9 +/- 9.8 mg/ml respectively prior to treatment with polyvinylpolypyrrolidone (PVPP) and 36.3 +/- 3.3 mg/ml and 238.0 +/- 2.5 mg/ml respectively after PVPP treatment of the extracts. The effect produced by C. asiatica is thus unlikely to be due to phenolic compounds. It may, however, be due to its two constituent triterpenoid glycosides madecassoside and asiaticoside which had IC50 values of 8.6 +/- 0.6 microM respectively. These values were comparable to their concentrations in the crude extract and to the IC50 of dithranol (5.1 +/- 0.4 microM). These results suggest that the potential use of C. asiatica extracts as a topical anti-psoriatic agent is worthy of further investigation.


  Development of a novel dosage form for intramuscular injection of titrated extract of Centella asiatica in a mixed micellar system.:Int J Pharm. 2001; 220(1-2):141-7 (ISSN: 0378-5173)

 Titrated extract of Centella asiatica (TECA), a drug used in treating systemic scleroderma, is poorly water-soluble. A conventional dosage form for the intramuscular injection of TECA, propylene glycol (PG)-based TECA solution, causes severe pain after intramuscular injection. To improve the solubility of TECA and reduce pain after injection, mixed micellar systems composed of 10% surfactant mixture (Tween 20 and Tween 85) and 90% phosphate-buffered saline, pH 7.0 (PBS) were prepared. As the ratio of Tween 20 to Tween 85 increased from 0:10 to 10:0, the solubility of TECA in the mixed micellar systems increased from 7- to 26-fold compared to that in PBS (pH 7.0). The droplet size of micelles gradually decreased with the increasing ratio of Tween 20 to Tween 85 from 0:10 to 4:6, followed by an abrupt decrease in size above the ratio of 6:4. Furthermore, the micellar systems prepared with Tween 20 and Tween 85 at the ratio of 6:4, 8:2 or 10:0 could solubilize TECA more than 10 mg/ml and the resultant droplet sizes were less than 2 microm. No significant changes were observed in the droplet sizes and asiaticoside contents in these micellar formulations during storage, indicating these systems are stable for at least 60 days. Their osmotic pressures were remarkably lower than those of PG-based TECA solution and similar to that of saline solution, irrespective of dilution ratios. Most importantly, they markedly reduced the number of writhes compared with PG-based TECA solution after injection to mice. All of these results suggest that these three TECA micellar formulations prepared with Tween 20 and Tween 85 improved the solubility of TECA and reduced pain following injection, possibly due to the decrease in osmotic pressure. Thus, these micellar formulations composed of optimum ratios of Tween 20 and Tween 85 may have a potential as dosage forms for the intramuscular injection of a poorly water-soluble TECA.

  Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy.:

 Angiology. 2001; 52 Suppl 2:S9-13 (ISSN: 0003-3197)Incandela L; Cesarone MR; Cacchio M; De Sanctis MT; Santavenere C; D'Auro MG; Bucci M;Belcaro G.Vascular Unit, Ealing Hospital, London, UK.
 Total triterpenic fraction of Centella asiatica (TTFCA) is effective in improving venous wall alterations in chronic venous hypertension and in protecting the venous endothelium. TTFCA is active on connective tissue modulation, improves the synthesis of collagen and other tissue proteins by modulating the action of fibroblasts in the vein wall, and stimulates collagen remodeling in and around the venous wall. This is due to the modulating action of TTFCA on fibroblasts as shown by experiments on the growth of human embryonal fibroblasts. TTFCA has a moderate in-vitro and in-vivo stimulating effect on collagen synthesis and, at higher dosages, an inhibition on the synthesis of collagen and acid mucopolysaccharides. Studies have indicated the role of TTFCA on the synthesis of specific venous wall elements by cell cultures of human embryonal fibroblasts. The tissue-stimulating action is shown by the increased collagen production independent from the stimulation of cell proliferation (this differentiates the action of TTFCA from cell growth factors). TTFCA is active on the microcirculation in venous and diabetic microangiopathy. Signs and symptoms of venous hypertension and edema are improved by treatment. The remodeling on collagen synthesis could be one of the possible mechanisms of actions of TTFCA in the remodeling of echolucent (soft; therefore, with risk of thrombosis and embolization) plaques at the carotid and femoral bifurcation. This compound is safe and well tolerated. In conclusion, several actions of TTFCA in vascular diseases makes the use of this compound very interesting in venous and arterial problems.

  Resources distribution and pharamacognostic identification of Centella asiatica (L.) urban produced in China.:

 Zhongguo Zhong Yao Za Zhi. 2000; 25(4):199-202 (ISSN: 1001-5302).Chen Y; Qin LP; Zheng HC; Zhang ZH.College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
 OBJECTIVE: To investigate the resources distribution and morphological histology of Centella asiatica distributed in China, and offer evidences for exploiting the plant resources and drafting the quality standards.
 METHOD: Sample collection, document investigation and microscopic section observation.
 RESULT: A table of resources distribution was worked out, the medicinal properties and the microscopic characteristics of the stem, leaf and stipe were described. CONCLUSION: This study supports the viewpoint of Urban and can be used as a reference for the quality standard of Centella asiation.

  Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats.:

 J Ethnopharmacol. 2002; 79(2):253-60 (ISSN: 0378-8741).Veerendra Kumar MH; Gupta YK.Department of Pharmacology, Neuropharmacology Laboratory, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India.
 Centella asiatica, a plant mentioned in Indian literature has been described to possess CNS effects such as stimulatory-nervine tonic, rejuvenant, sedative, tranquilizer and intelligence promoting property. In the present study aqueous, methanolic and chloroform extracts of C. asiatica were investigated for their effect on cognitive functions in rats. Male Wistar rats of 200-250 g were used to study the effect on learning and memory by using shuttle box, step through, step down and elevated plus maze paradigms. Only the aqueous extract of whole plant (200 mg/kg for 14 days) showed an improvement in learning and memory in both shuttle box and step through paradigms. Therefore, further experiments were conducted with aqueous extract using 100, 200 and 300 mg/kg doses in different paradigms of learning and memory. All doses of aqueous extract increased the number of avoidances in shuttle box and prolonged the step through latency in step through apparatus in a dose dependent manner, while only two doses 200 and 300 mg/kg of aqueous extract showed significant increase in the step down latency in step down apparatus and transfer latency (TL) in elevated plus maze. Among doses of aqueous extract tested on oxidative stress parameters, only 200 and 300 mg/kg showed a significant decrease in the brain levels of malondialdehyde (MDA) with simultaneous significant increase in levels of glutathione. There was a significant increase in the levels of catalase at the 300 mg/kg but no significant change in superoxide dismutase (SOD) levels were observed. The present findings indicate that the aqueous extract of C. asiatica has cognitive enhancing effect and an antioxidant mechanism is involved.

  Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds.:

 Eur J Dermatol. 1999; 9(4):289-96 (ISSN: 1167-1122).Maquart FX; Chastang F; Simeon A; Birembaut P; Gillery P; Wegrowski Y.Laboratory of Biochemistry, UPRESA CNRS 6021, IFR-53 Biomol??cules, Faculty of Medicine, Reims, France. fmaquart@chu-reims.fr
 Titrated Extract from Centella asiatica (TECA) is a drug which has been used for many years in Europe for the treatment of wound healing defects. It is a reconstituted mixture of 3 triterpenes extracted from the plant, asiatic acid, madecassic acid and asiaticoside. In this report, we studied the effects of TECA and its separated components in the wound chamber model described by Schilling et al. Stainless steel wound chambers were surgically inserted under the skin of rats and received serial injections of either TECA or its purified components. Chambers were collected at days 7, 14, 21 or 28 for biochemical analysis or histological examination. TECA-injected wound chambers were characterized by increased dry weight, DNA, total protein, collagen and uronic acid contents. Peptidic hydroproline was also increased, showing an increased remodeling of the collagen matrix in the wound. The 3 purified components of TECA were all able to reproduce the effects of the complete drug, with some differences depending on the product. Asiatic acid and asiaticoside were the most active of the 3 triterpenes. Asiaticoside exerted a preferential stimulation of collagen synthesis and was active at low doses only. In addition to collagen, the 3 components were also able to stimulate glycosaminoglycan synthesis.


  Effectiveness of the combination of alpha tocopherol, rutin, melilotus, and centella asiatica in the treatment of patients with chronic venous insufficienc.:

 Minerva Cardioangiol. 2001; 49(2):159-63 (ISSN: 0026-4725).Cataldi A; Gasbarro V; Viaggi R; Soverini R; Gresta E; Mascoli F.Unit?? Operativa Chirurgia Vascolare, Arcispedale S. Anna, Turin, Italy. alberto.cataldi@galactica.it
 BACKGROUND: The aim of this comparative clinical study was to evaluate the efficacy of the association of alphatocopherol, rutin, melilotus officinalis, and centella asiatica with oral administration in patients with chronic venous insufficiency.
 METHODS: Thirty patients with chronic venous insufficiency have been randomized in two groups of fifteen subjects (control and treatment group). During the period of treatment the patients didn't wear elastocompressive stockings. The therapeutic efficacy and the clinical tolerability of this association have been valued with clinical-instrumental evaluations and by a control after 15 and 30 days. Functional bothers, cramps and the edema have been valued in function presence and of their gravity with a clinical-score between 0 and 4. RESULTS: At the end of the observation period, a significant improvement of the clinical simptomatology was obtained, characterised by a diminution of the sovrafascial edema.
 CONCLUSIONS: The present study confirms previous clinical experiences regarding the described treatment and suggests its application in chronic venous insufficiency.

  Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model.:

 Angiology. 2001; 52 Suppl 2:S61-7 (ISSN: 0003-3197)Incandela L; Belcaro G; De Sanctis MT; Cesarone MR; Griffin M; Ippolito E; Bucci M;Cacchio M.Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.
 A single-blind, placebo-controlled, randomized study was performed on the effects of different doses of the total triterpenic fraction of Centella asiatica (TTFCA) in patients with venous hypertensive microangiopathy. A combined microcirculatory model that considers laser Doppler flowmetry (LDF) and transcutaneous oxygen (PO2), transcutaneous carbon dioxide tension (PCO2) measurements was combined with the symptom evaluation. LDF tests included the baseline resting flow, the venoarteriolar reflex, and the variation of flow related to the temperature increase. All tests provided a significant difference between drug-treated groups and the placebo group, thereby allowing a distinction to be made between the higher (120 mg daily) and the lower (60 mg daily) dose of TTFCA. Transcutaneous PO2-PCO2 measurements were significantly modified by drug treatments, while no variation could be detected in the placebo group. Important symptomatologic effects (evaluated by subjective scores) followed TTFCA administration, especially at the higher dose level, while no effect was obtained with placebo. The trend of symptom evaluation paralleled the results of objective tests of our microcirculatory model, providing evidence that this model can reveal effects of venoactive drugs on venous hypertensive microangiopathy. TTFCA displays a significant activity. Doses as high as 120 mg daily may be safely used in venous hypertension.

  Advanced formulation and pharmacological activity of hydrogel of the titrated extract of C. asiatica.:

 Arch Pharm Res. 2005; 28(4):502-8 (ISSN: 0253-6269).Hong SS; Kim JH; Li H; Shim CK.Department of Pharmaceutics, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
 Titrated extract of Centella asiatica (TECA) contains three principal ingredients, asiaticoside (AS), asiatic acid (AA), and madecassic acid (MA). These components are known to be clinically effective on systemic scleroderma, abnormal scar formation, and keloids. However, one problem associated with administration of TECA is its low solubility in aqueous as well as oil medium. In this study, various nonionic surfactants and bile salts as anionic surfactant were tested and screened for solubilizing TECA with a view to developing topical hydrogel type of ointment which is stable physicochemically, and has better pharmacological effects. When TECA was incorporated into various nonionic surfactant systems, labrasol had the most potent capacity for solubilizing TECA. In cases of bile salt systems, Na-deoxycholate (Na-DOC) had foremost solubilizing capacity, even more than labrasol. In differential scanning calorimetric study, the peaks of AA, MA, AS and Na-DOC disappeared at the coprecipitate of 1% TECA and 1% Na-DOC, suggesting the optimum condition of Na-DOC for solubilizing TECA. When the physicochemical stability of hydrogel containing this mixture was assessed, it was stable at room temperature for at least one month. Pharmacologically it significantly decreased the size of wound area at the 9th day when applied to the wound area of rat dorsal skin. Taken together, solubility of TECA was dramatically improved by using nonionic and anionic surfactant systems, and Na-DOC was found to be the most effective solubilizer of TECA in formulating a TECA-containing hydrogel typed ointment. Moreover this gel was considered to be applicable to clinical use for wound healing effect.

  Phlebotonics for venous insufficiency.:

 Cochrane Database Syst Rev. 2005; (3):CD003229 (ISSN: 1469-493X).Martinez MJ; Bonfill X; Moreno RM; Vargas E; Capell?? D.Hospital de la Santa Creu i Sant Pau, Iberoamerican Cochrane Center, Service of Epidemiology, Sant Antoni M. Claret, 171, Barcelona, Spain, 08041. mmartinezz@hsp.santpau.es
 BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by inadequate blood flow through the veins, usually in the lower limbs. It can result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Sufferers may also experience swelling and ulcers. Phlebotonics are a class of drugs that are often used to treat CVI.
 OBJECTIVES: To assess the efficacy of oral or topical phlebotonics. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group trials register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2005), MEDLINE (January 1966 to April 2005), EMBASE (January 1980 to April 2005) and reference lists of articles. We also contacted pharmaceutical companies.
 SELECTION CRITERIA: Randomised, double blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in CVI patients at any stage of the disease.
 DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. The effects of treatment were estimated by relative risk (RR) or by standardised mean differences (SMD) by applying a random effects statistical model. Sensitivity analyses were also performed.
 MAIN RESULTS: Fifty-nine RCTs of oral phlebotonics were included, but only 44 trials involving 4413 participants contained quantifiable data for the efficacy analysis: 23 of rutosides, ten of hidrosmine and diosmine, six of calcium dobesilate, two of centella asiatica, one of french maritime pine bark extract, one of aminaftone and one of grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Outcomes included oedema, venous ulcers, trophic disorders, subjective symptoms (pain, cramps, restless legs, itching, heaviness, swelling and paraesthesias), global assessment measures and side effects. The results of many variables were heterogeneous. Phlebotonics showed some global benefit (i.e. oedema reduction) (relative risk 0.72, 95% confidence interval 0.65 to 0.81). The benefit for the remaining CVI signs and symptoms must be evaluated by phlebotonic group. There were no quantifiable data on quality of life.
 AUTHORS' CONCLUSIONS: There is not enough evidence to globally support the efficacy of phlebotonics for chronic venous insufficiency. There is a suggestion of some efficacy of phlebotonics on oedema but this is of uncertain clinical relevance. Due to the limitations of current evidence, there is a need for further randomised, controlled clinical trials with greater attention paid to methodological quality.

  Asiaticoside induces human collagen I synthesis through TGFbeta receptor I kinase (TbetaRI kinase)-independent Smad signaling.:

 Planta Med. 2006; 72(4):324-8 (ISSN: 0032-0943).Lee J; Jung E; Kim Y; Park J; Park J; Hong S; Kim J; Hyun C; Kim YS; Park D.Biospectrum Life Science Institute, Gunpo City, Gyunggi Do, Korea.
 Skin aging appears to be principally related to a decrease in the levels of type I collagen, the primary component of the skin dermis. Asiaticoside, a saponin component isolated from Centella asiatica, has been shown to induce type I collagen synthesis in human dermal fibroblast cells. However, the mechanism underlying asiaticoside-induced type I collagen synthesis, especially at a molecular level, remains only partially understood. In this study, we have attempted to characterize the action mechanism of asiaticoside in type I collagen synthesis. Asiaticoside was determined to induce the phosphorylation of both Smad 2 and Smad 3. In addition, we detected the asiaticoside-induced binding of Smad 3 and Smad 4. In a consistent result, the nuclear translocation of the Smad 3 and Smad 4 complex was induced via treatment with asiaticoside, pointing to the involvement of asiaticoside in Smad signaling. In addition, SB431542, an inhibitor of the TGFbeta receptor I (TbetaRI) kinase, which is known to be an activator of the Smad pathway, was not found to inhibit both Smad 2 phosphorylation and Type 1 collagen synthesis induced by asiaticoside. Therefore, our results show that asiaticoside can induce type I collagen synthesis via the activation of the TbetaRI kinase-independent Smad pathway.


  Asiatic acid induces apoptosis in SK-MEL-2 human melanoma cells.:

 Cancer Lett. 2005; 218(1):81-90 (ISSN: 0304-3835).Park BC; Bosire KO; Lee ES; Lee YS; Kim JA.College of Pharmacy, Yeungnam University, Gyongsan 712-749, South Korea.
 Asiatic acid (AA) is a pentacyclic triterpene found in Centella asiatica. In the present study, the mechanism of anticancer effect of AA on skin cancer was investigated. AA decreased viability and induced apoptosis in human melanoma SK-MEL-2 cells in a time- and dose-dependent manner. AA also markedly increased intracellular reactive oxygen species (ROS) level and enhanced the expression of Bax but not Bcl-2 protein in the cells. In addition, AA-induced activation of caspase-3 activity in a dose-dependent manner. Pretreatment with Trolox, an antioxidant, significantly blocked the induction of Bax and activation of caspase-3 in AA-treated cells. Furthermore, Ac-DEVD-CHO, a specific caspase-3 inhibitor, and Trolox prevented the AA-induced apoptosis. AA did not elevate p53 nuclear protein levels that are present in a mutant form in SK-MEL-2 cells. These results suggest that AA-induced apoptosis may be mediated through generation of ROS, alteration of Bax/Bcl-2 ratio and activation of caspase-3, but p53-independent. These results further suggest that AA may be a good candidate for the therapeutic intervention of human skin cancer.

  Nutritional support for wound healing.:

 Altern Med Rev. 2003; 8(4):359-77 (ISSN: 1089-5159).MacKay D; Miller AL.Thorne Research, Inc., PO Box 25, Dover, ID 83825, USA. duffy@thorne.com
 Healing of wounds, whether from accidental injury or surgical intervention, involves the activity of an intricate network of blood cells, tissue types, cytokines, and growth factors. This results in increased cellular activity, which causes an intensified metabolic demand for nutrients. Nutritional deficiencies can impede wound healing, and several nutritional factors required for wound repair may improve healing time and wound outcome.
 Vitamin A is required for epithelial and bone formation, cellular differentiation, and immune function. Vitamin C is necessary for collagen formation, proper immune function, and as a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the skin; however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain reduces edema, bruising, pain, and healing time following trauma and surgical procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic acid production in the wound. Adequate dietary protein is absolutely essential for proper wound healing, and tissue levels of the amino acids arginine and glutamine may influence wound repair and immune function. The botanical medicines Centella asiatica and Aloe vera have been used for decades, both topically and internally, to enhance wound repair, and scientific studies are now beginning to validate efficacy and explore mechanisms of action for these botanicals. To promote wound healing in the shortest time possible, with minimal pain, discomfort, and scarring to the patient, it is important to explore nutritional and botanical influences on wound outcome.

  Asiaticoside induction for cell-cycle progression, proliferation and collagen synthesis in human dermal fibroblasts.:

 Int J Dermatol. 2004; 43(11):801-7 (ISSN: 0011-9059).Lu L; Ying K; Wei S; Fang Y; Liu Y; Lin H; Ma L; Mao Y.From the State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China. luluo@vip.163.com
 Asiaticoside, isolated from Centella asiatica, promotes fibroblast proliferation and extracullar matrix synthesis in wound healing. The precise mechanism, however, in molecular and gene expression levels still remains partially understood. Using cDNA microarray technology, the alternation of genes expression profiles was determined in a human dermal fibroblast in vitro in the presence of asiaticoside (30 microg/ml). Fifty-four genes, with known functions for cell proliferation, cell-cycle progression and synthesis of the extracellular matrix, were significantly up-regulated in our "whole-genes nest" expression profile at various timepoints. Furthermore, mRNA levels and protein productions of certain genes responsible for extracellular matrix (ECM) synthesis (e.g. encoding type I and type III collagen proteins) were evaluated by Northern blot and radioimmunoassay, respectively. As a result, there is a close correlation among the gene profile, mRNA and protein production in the cells response to asiaticoside stimulation. This information could be used for exploring the target genes in response to asiaticoside in fibroblasts.

  Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants.:

 Phytomedicine. 2000; 6(6):411-9 (ISSN: 0944-7113).Yoosook C; Bunyapraphatsara N; Boonyakiat Y; Kantasuk C.Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand. sccys@mahidol.ac.th
 A number of Thai medicinal plants, recommended as remedies for herpesvirus infection and have been used in primary health care were investigated for their intracellular activities against herpes simplex viruses (HSV). Centella asiatica L., Maclura cochinchinensis Cornor, and Mangifera indica L. contained both anti-HSV-1 and -2 activities, as determined by plaque inhibition assay. An inhibition of the production of infectious HSV-2 virions from infected Vero cells could also be demonstrated. Combinations of each of these reconstituted extracts with 9-(2-hydroxyethoxymethyl) guanosine (acyclovir; ACV) resulted either in subadditive, additive, or synergistic interaction, against HSV-2, depending on the dose of ACV used; mixture of C. asiatica and M. indica exerted an additive effect in a similar assay. Furthermore, the inhibitory effects of these plant extracts were also substantiated by flow cytometric analysis of virus-specific antigens in the infected cells. The active constituent present in C. asiatica extract was determined to be asiaticoside while in M. indica was mangiferin. Thus, these data suggest therapeutic potential of these plant extracts.

  Extraction and analysis of cosmetic active ingredients from an anti-cellulitis transdermal delivery system by high-performance liquid chromatography.:

 J Chromatogr Sci. 1999; 37(2):51-5 (ISSN: 0021-9665).Morganti P; Fionda A; Elia U; Tiberi L.Mavi Sud, Research & Development Laboratories,Aprilia, Italy.
 A new transdermal delivery system that controls cellulitis is evaluated using reversed-phase high-performance liquid chromatography coupled with photodiode array detection. An extraction procedure and the validation of the analytical method to assay the active excipients from the Centella asiatica plant (asiaticoside, madacessic acid, and asiatic acid) are described. Excellent results ae obtained in terms of linearity, accuracy, and specificity of the analytical method.


  Hemorrhoids and varicose veins: a review of treatment options.:

 Altern Med Rev. 2001; 6(2):126-40 (ISSN: 1089-5159).MacKay D.Thorne Research, 4616 SE 30th, Portland, OR 97202, USA.mackaynd@earthlink.net
 Hemorrhoids and varicose veins are common conditions seen by general practitioners. Both conditions have several treatment modalities for the physician to choose from. Varicose veins are treated with mechanical compression stockings. There are several over-the-counter topical agents available for hemorrhoids. Conservative therapies for both conditions include diet, lifestyle changes, and hydrotherapy which require a high degree of patient compliance to be effective. When conservative hemorrhoid therapy is ineffective, many physicians may choose other non-surgical modalities: injection sclerotherapy, cryotherapy, manual dilation of the anus, infrared photocoagulation, bipolar diathermy, direct current electrocoagulation, or rubber band ligation. Injection sclerotherapy is the non-surgical treatment for primary varicose veins. Non-surgical modalities require physicians to be specially trained, own specialized equipment, and assume associated risks. If a non-surgical approach fails, the patient is often referred to a surgeon. The costly and uncomfortable nature of treatment options often lead a patient to postpone evaluation until aggressive intervention is necessary. Oral dietary supplementation is an attractive addition to the traditional treatment of hemorrhoids and varicose veins. The loss of vascular integrity is associated with the pathogenesis of both hemorrhoids and varicose veins. Several botanical extracts have been shown to improve microcirculation, capillary flow, and vascular tone, and to strengthen the connective tissue of the perivascular amorphous substrate. Oral supplementation with Aesculus hippocastanum, Ruscus aculeatus, Centella asiatica, Hamamelis virginiana, and bioflavonoids may prevent time-consuming, painful, and expensive complications of varicose veins and hemorrhoids.

  The microcirculatory activity of Centella asiatica in venous insufficiency. A double-blind study.:

 Minerva Cardioangiol. 1994; 42(6):299-304 (ISSN: 0026-4725).Cesarone MR; Laurora G; De Sanctis MT; Incandela L; Grimaldi R; Marelli C; Belcaro G.Istituto di Clinica Cardiovascolare, Universit?? degli Studi G. D'Annunzio, Chieti.
 In 87 patients with chronic venous hypertensive microangiopathy the efficacy of oral FTTCA (Centella asiatica) administered for 60 days was tested. The microcirculatory effects of two dosages (30 mg bid and 60 mg bid) versus placebo was assessed in a double blind study. The compound was well tolerated and no unwanted effects were observed. Microcirculatory parameters--peri-malleolar skin flux at rest (RF) and transcutaneous PO2 and PCO2--improved as did the abnormally increased RF, PCO2 decreased and PO2 increased in comparison with values measured at inclusion. These results confirm the efficacy of FTTCA in venous hypertensive microangiopathy. Furthermore the effects of FTTCA appear to be dose-related.

  Activity of Centella asiatica in venous insufficiency.:

 Minerva Cardioangiol. 1992; 40(4):137-43 (ISSN: 0026-4725).Cesarone MR; Laurora G; De Sanctis MT; Belcaro G.Clinica Cardiovascolare,Universit?? degli Studi G. D'Annunzio, Chieti.
 In this a review concerning TTFCA, its effects on metabolism in the connective tissue of the vascular wall and on the microcirculation are presented and discussed. This compound is effective in venous insufficiency, reducing ankle edema, foot swelling, capillary filtration rate and by improving microcirculatory parameters (RF, VAR PO2-PCO2). TTFCA displays a significant activity in venous hypertensive microangiopathy and its effects are dose-dependent.


  Scientific References:

  1.Gotu Kola Centella asiatica,the Goddess of Supreme Wisdom.
  2.Research Update of Gotu Kola Centella asiatica,the Goddess of Supreme Wisdom.