Phytochemical info of FeverFew or Tanacetum parthenium
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Definition:FeverFew or Tanacetum parthenium are majorly composed of
Chemical information disclosed as following table:
Research Update:FeverFew or Tanacetum parthenium.
Identification of antioxidant phenolic compounds in feverfew (Tanacetum parthenium) by HPLC-ESI-MS/MS and NMR:Phytochem Anal. 2007 Sep;18(5):401-10.Wu C, Chen F, Wang X, Wu Y, Dong M, He G, Galyean RD, He L, Huang G.Department of Food Science and Human Nutrition, Clemson University, Clemson, SC 29634, USA. changqi@clemson.edu
Antioxidant polyphenolic acids in the medicinal herb feverfew (Tanacetum parthenium) were isolated through in vitro bioassay-orientated antioxidant tests in response to 1,1-diphenyl-2-picrylhydrazyl (DPPH*) free radical scavenging and Fe(2+)-chelating activities. Purification of the active compounds and their structural elucidation involved a variety of techniques including open-column chromatography, HPLC, GC-MS, LC-MS and NMR. Major compounds with potent DPPH* scavenging activities were characterised as 3,5-, 4,5- and 3,4-di-O-caffeoylquinic acids (DCQAs). This is the first report of DCQAs found in feverfew.
Antiproliferative activity of parthenolide against three human cancer cell lines and human umbilical vein endothelial cells.:Pharmacol Rep. 2007 Mar-Apr;59(2):233-7.Parada-Turska J, Paduch R, Majdan M, Kandefer-Szersze¨½ M, Rzeski W.Department of Rheumatology and Connective Tissue Diseases, Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland. jolanta.turska@am.lublin.pl.
Parthenolide is a major sesquiterpene lactone derived from feverfew (Tanacetum parthenium) with known anti-inflammatory activity. Moreover, the anticancer potential of this compound was suggested. In this study, we determined the effect of parthenolide on proliferation of three human cancer cell lines: human lung carcinoma (A549), human medulloblastoma (TE671), human colon adenocarcinoma (HT-29) and human umbilical vein endothelial cells (HUVEC) in vitro. Cell proliferation was assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC(50) value (the concentration of drug necessary to induce 50% inhibition) together with confidence limits was calculated. Parthenolide inhibited proliferation of all three types of cancer cells (A549, TE671, HT-29) and HUVEC with the following IC(50) values (in muM): 4.3, 6.5, 7.0 and 2.8, respectively. Thus, the antiproliferative potential of parthenolide was confirmed.
Parthenolide induces significant apoptosis and production of reactive oxygen species in high-risk pre-B leukemia cells.:Cancer Lett. 2007 Aug 28;254(1):119-27. Epub 2007 Apr 30.Zunino SJ, Ducore JM, Storms DH.United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, University of California, Davis, CA 95616, USA. szunino@whnrc.usda.gov
We investigated whether parthenolide, the principal bioactive component of the herb feverfew (Tanacetum parthenium) induced apoptosis in pre-B acute lymphoblastic leukemia (ALL) lines, including cells carrying the t(4;11)(q21;q23) chromosomal translocation. Parthenolide induced rapid apoptotic cell death distinguished by loss of nuclear DNA, externalization of cell membrane phosphatidylserine, and depolarization of mitochondrial membranes at concentrations ranging from 5 to 100 microM. Using reactive oxygen species (ROS)-specific dyes, an increase in nitric oxide and superoxide anion was detected in the cells by 4 h after exposure to parthenolide. Parthenolide-induced elevation of hypochlorite anion was observed only in the two t(4;11) lines. These data suggest parthenolide may have potential as a potent and novel therapeutic agent against pre-B ALLs.
Quantitative estimation of parthenolide in Tanacetum parthenium (L.) Schultz-Bip. cultivated in Egypt.:J AOAC Int. 2007 Jan-Feb;90(1):21-7.El-Shamy AM, El-Hawary SS, Rateb ME.Cairo University, Faculty of Pharmacy, Pharmacognosy Department, Kasr El-Aini St, 11562, Cairo, Egypt.
Parthenolide, a germacranolide-type sesquiterpene lactone, was estimated in Tanacetum parthenium (L.) cultivated in Egypt by using colorimetric, planar chromatographic, and high-performance liquid chromatographic (HPLC) methods. Parthenolide levels in the open-field herb and aseptically germinated shoots were also compared by using the HPLC method. Parthenolide was produced and estimated for the first time in the callus culture of the plant. In addition, 2 Egyptian market preparations were analyzed for their parthenolide content by using the HPLC method. The relative standard deviations were 0.093, 0.095, and 0.098% (n = 5, 5, and 7, respectively), and the corresponding recoveries were 98.2, 98.9, and 99.4% for the colorimetric, planar chromatographic, and HPLC determinations, respectively.
Natural considerations for skin of color.:Cutis. 2006 Dec;78(6 Suppl):2-19. Review.Baumann L, Rodriguez D, Taylor SC, Wu J.University of Miami Cosmetic Center, Florida, USA.
Changing US demographics indicate that dermatologists will treat an increasing number of individuals of color. Early research on cutaneous anatomy and physiology was performed mostly in white populations. However, new research is elucidating similarities and differences in skin of color and white skin with regard to skin barrier, pigmentation, and sensitivity. Two of the most important issues are skin lightening and brightening. Products for use on skin of color typically should be gentle because of the proclivity of more deeply pigmented skin to develop pigmentary abnormalities in response to skin irritation or trauma. Increasing patient interest in natural remedies has been matched by research on the use of natural ingredients in dermatology. The relative gentleness of many of these products, coupled with excellent efficacy, makes natural ingredients such as soy and licorice excellent choices in the treatment of disorders such as postinflammatory hyperpigmentation (PIH) and melasma. For daily skin care, ingredients such as oatmeal and feverfew are good choices for gentle cleansing and moisturizing of dry, sensitive, or ashy skin. Sun protection is an increasing concern due to rising rates of melanoma. Several botanical products are useful in augmenting photoprotection with conventional sunscreens.
Parthenolide inhibits IkappaB kinase, NF-kappaB activation, and inflammatory response in cystic fibrosis cells and mice.:Am J Respir Cell Mol Biol. 2007 Jun;36(6):728-36. Epub 2007 Feb 1.Saadane A, Masters S, DiDonato J, Li J, Berger M.Department of Pediatrics, Rainbow Babies and Childrens' Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Cystic fibrosis (CF) is characterized by prolonged and excessive inflammatory responses in the lung and increased activation of NF-kappaB. Parthenolide is a sesquiterpene lactone derived from the plant feverfew, which has been used in folk medicine for anti-inflammatory activity. Several studies suggest that this compound inhibits the NF-kappaB pathway, but the exact site is controversial. We hypothesized that parthenolide might ameliorate the excessive inflammatory response in CF models by inhibiting activation of NF-kappaB. This was tested in vitro, using two pairs of cell lines with defective versus normal CF transmembrane conductance regulator (CFTR) (antisense/sense transfected 16 HBE and IB-3/S9), and in vivo, using CFTR-knockout (KO) mice. All cell lines were pretreated with parthenolide and then stimulated with IL-1beta and/or TNF. Parthenolide significantly inhibited IL-8 secretion induced by these cytokines and prevented NF-kappaB activation, IkappaBalpha degradation, and IkappaB Kinase complex activity. CFTR-KO and wild-type mice were pretreated with parthenolide or vehicle alone then challenged intratracheally with LPS. Bronchoalveolar lavage was performed 3, 6, and 8 h later. Parthenolide pretreatment inhibited PMN influx as well as cytokine and chemokine production. This was also associated with inhibition of IkappaBalpha degradation and NF-kappaB activation. We thus conclude that parthenolide inhibits IkappaB kinase, resulting in stabilization of cytoplasmic IkappaBalpha, which in turn leads to inhibition of NF-kappaB translocation and attenuation of subsequent inflammatory responses. IkappaB kinase may be a good target, and parthenolide and/or feverfew might be promising treatments for the excessive inflammation in CF.
Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis: a prospective, open-label study:Clin Drug Investig. 2006;26(5):287-96.Shrivastava R, Pechadre JC, John GW.Naturveda - Vitro-Bio Research Institute, ZAC de Lavaur, Issoire, France.
BACKGROUND: Tanacetum parthenium (feverfew) has been used traditionally to treat migraine, and although its mechanism of action is not fully understood, serotonin 5-HT receptor blocking effects have been suggested. T. parthenium and Salix alba (white willow) either alone or in combination (Mig-RL) were recently shown to inhibit binding to 5-HT(2A/2C) receptors; T. parthenium failed to recognise 5-HT(1D) receptors, whereas S. alba or the combination did. It was hypothesised that S. alba in combination with T. parthenium may provide superior migraine prophylactic activity compared with T. parthenium alone. METHODS: A prospective, open-label study was performed in 12 patients diagnosed with migraine without aura. Twelve weeks' treatment with T. parthenium 300 mg plus S. alba 300 mg (Mig-RL) twice daily was administered to determine the effects of therapy on migraine attack frequency (primary efficacy criterion), intensity and duration (secondary efficacy criteria), and quality of life, together with tolerability for patients. RESULTS: Attack frequency was reduced by 57.2% at 6 weeks (p < 0.029) and by 61.7% at 12 weeks (p < 0.025) in nine of ten patients, with 70% patients having a reduction of at least 50%. Attack intensity was reduced by 38.7% at 6 weeks (p < 0.005) and by 62.6% at 12 weeks (p < 0.004) in ten of ten patients, with 70% of patients having a reduction of at least 50%. Attack duration decreased by 67.2% at 6 weeks (p < 0.001) and by 76.2% at 12 weeks (p < 0.001) in ten of ten patients. Two patients were excluded for reasons unrelated to treatment. Self-assessed general health, physical performance, memory and anxiety also improved by the end of the study. Mig-RL treatment was well tolerated and no adverse events occurred. CONCLUSION: The remarkable efficacy of Mig-RL in not only reducing the frequency of migraine attacks but also their pain intensity and duration in this trial warrants further investigation of this therapy in a double-blind, randomised, placebo-controlled investigation involving a larger patient population.
Quantification of parthenolide in Tanacetum species by LC-UV/LC-MS and microscopic comparison of Mexican/US feverfew samples:Pharmazie. 2006 Jul;61(7):590-4.Avula B, Navarrete A, Joshi VC, Khan IA.National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, The University of Mississippi, MS 38677, USA.
LC-UV and LC-MS methods have been developed which permit the analysis of parthenolide in different Mexican/US feverfew samples and commercial products. The study was undertaken to confirm the presence of parthenolide in Mexican plant samples and its comparison with US feverfew samples. The best results were obtained with a Phenomenex Luna C18 (2) column using gradient mobile phase of water and acetonitrile:methanol (9 : 1). Elution was run at a flow rate of 1.0 mL per min and ultraviolet detection at 210 nm. The results obtained using LC-UV were comparable to those obtained using LC-MS. Parthenolide was detected in all the samples analyzed and is the major chemical constituent of feverfew. The samples collected in Oaxaca, Mexico (0.28%) and Puebla, Mexico (0.25%) showed the highest content of parthenolide. All Parthenium samples were also examined under light and fluorescent microscopy.
A reproductive screening test of feverfew: is a full reproductive study warranted?:Reprod Toxicol. 2006 Nov;22(4):688-93. Epub 2006 Jun 15.Yao M, Ritchie HE, Brown-Woodman PD.School of Biomedical Sciences, Faculty of Health Sciences, The University of Sydney, Lidcombe, NSW, Australia.
Feverfew is currently used in the treatment of migraine and arthritis. It is traditionally contraindicated in pregnancy but there are no studies confirming this warning. An in vivo and in vitro preliminary screen was performed using a rat model: five female rats were orally dosed with 839 mg/kg feverfew daily on either gestation days (GD) 1-8 or 8-15. On GD20, rats were sacrificed and fetuses, placentae and ovaries were collected. The fetuses were weighed and examined for malformations. While maternal weight gain appeared to be reduced, ANCOVA analysis suggested that the difference was due to litter size, rather than treatment. Pre-implantation loss appeared increased but this was not statistically significant in the feverfew GD1-8 group. Fetuses exposed to feverfew from GD8-15 were smaller than ethanol controls perhaps as a result of the increased frequency of runts in treated litters. Feverfew induced toxicity when GD10.5 embryos were cultured for 26 h in rat serum to which extract was added. The results of the present preliminary study suggest that a comprehensive reproductive study of feverfew is warranted.
Dereplication of pentacyclic triterpenoids in plants by GC-EI/MS:Phytochem Anal. 2006 Mar;17(2):102-6.Gu JQ, Wang Y, Franzblau SG, Montenegro G, Timmermann BN.Department of Pharmacology and Toxicology, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Three common plant-derived pentacyclic triterpenoids, oleanolic acid (1), betulinic acid (2) and ursolic acid (3), have been found to exhibit moderate anti-tubercular activity in a microplate alamar blue assay. In order to facilitate the discovery of novel anti-tubercular leads with diverse chemical structures, a new and rapid GC-EI/MS method was developed simultaneously and unambiguously to dereplicate 1-3 as their methyl esters with limits of detection of 25.6, 26.9 and 26.8 ng, respectively.
Antiproliferative activities of parthenolide and golden feverfew extract against three human cancer cell lines.:J Med Food. 2006 Spring;9(1):55-61.Wu C, Chen F, Rushing JW, Wang X, Kim HJ, Huang G, Haley-Zitlin V, He G.Department of Food Science and Human Nutrition, Clemson University, Clemson, South Carolina 29634, USA.
The medicinal herb feverfew [Tanacetum parthenium (L.) Schultz-Bip.] has long been used as a folk remedy for the treatment of migraine and arthritis. Parthenolide, a sesquiterpene lactone, is considered to be the primary bioactive compound in feverfew having anti-migraine, anti-tumor, and anti-inflammatory properties. In this study we determined, through in vitro bioassays, the inhibitory activity of parthenolide and golden feverfew extract against two human breast cancer cell lines (Hs605T and MCF-7) and one human cervical cancer cell line (SiHa). Feverfew ethanolic extract inhibited the growth of all three types of cancer cells with a half-effective concentration (EC50) of 1.5 mg/mL against Hs605T, 2.1 mg/mL against MCF-7, and 0.6 mg/mL against SiHa. Among the tested constituents of feverfew (i.e., parthenolide, camphor, luteolin, and apigenin), parthenolide showed the highest inhibitory effect with an EC50 against Hs605T, MCF-7, and SiHa of 2.6 microg/mL, 2.8 microg/mL, and 2.7 microg/mL, respectively. Interactions between parthenolide and flavonoids (apigenin and luteolin) in feverfew extract also were investigated to elucidate possible synergistic or antagonistic effects. The results revealed that apigenin and luteolin might have moderate to weak synergistic effects with parthenolide on the inhibition of cancer cell growth of Hs605T, MCF-7, and SiHa.
Parthenium dermatitis treated with azathioprine weekly pulse doses.:Indian J Dermatol Venereol Leprol. 2006 Jan-Feb;72(1):24-7.Verma KK, Bansal A, Sethuraman G.Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India. prokverma@hotmail.com
BACKGROUND: Parthenium dermatitis is a serious problem in India. Corticosteroids are the mainstay of treatment but the prolonged use of corticosteroids can cause serious side effects. Azathioprine used in daily doses has been shown to be effective. AIM: We have evaluated the effectiveness of azathioprine weekly pulse doses for the treatment of parthenium dermatitis. METHODS: Twelve patients, ten males and two females, aged between 39 and 65 years (mean +/- SD = 53.5 +/- 8.7) having air-borne contact dermatitis to Parthenium hysterophorus for 3-19 years (mean = 6.33) were included in the study. The diagnosis in each patient was confirmed by patch-testing. The severity of the disease was determined by clinical severity score (CSS) on the basis of erythema, itching, type of lesions, and areas of body involved. RESULTS: The pretreatment CSS in these patients varied from 29.7 to 55.5 (mean +/- SD: 40.40 +/- 7.95). After clinical and laboratory evaluation, the patients were treated with 300-mg azathioprine once-weekly doses for 6 months. Clinical and laboratory evaluations were repeated at weeks 1, 2, and then every 4 weeks until the end of therapy to evaluate the therapeutic response and side effects. The response was excellent (80-100% clearance of disease) in seven (58.33%) patients and good (60% clearance) in five (41.66%) patients. The post-treatment CSS decreased from the mean +/- SD of 40.4 +/- 7.95 to 10.9 +/- 8.43 (P = 0.002). There were no significant side effects of the therapy. CONCLUSIONS: In this preliminary open study, azathioprine in weekly pulse doses has been found to be effective without any serious adverse effects in the treatment of parthenium dermatitis. The cost of therapy with this regimen is reduced by 60%.
Treatment of rosacea with herbal ingredients:J Drugs Dermatol. 2006 Jan;5(1):29-32. Review.Wu J.drwu@drjessicawu.com
Since rosacea is a chronic disease and many patients find prescription therapies unsatisfactory, they frequently turn to herbal ingredients for relief of their persistent facial redness. The most useful and frequently used herbal compounds include licorice, feverfew, green tea, oatmeal, lavender, chamomile, tea tree oil, and camphor oil. The utility of most of these herbs is based on their purported anti-inflammatory properties. Some of these herbs have proven effects, many have potential benefits, and some may aggravate rosacea. Due to the fact that many patients fail to inform their physicians about their use of herbal ingredients, dermatologists should be aware of what patients may be using and be able to advise them about the efficacy of these ingredients or the potential for adverse effects.
Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention--a randomized, double-blind, multicentre, placebo-controlled study.:Cephalalgia. 2005 Nov;25(11):1031-41.Diener HC, Pfaffenrath V, Schnitker J, Friede M, Henneicke-von Zepelin HH.Neurologische Universit?tsklinik, Essen, Germany. h.diener@uni-essen.de
The efficacy and tolerability of a CO(2)-extract of feverfew (MIG-99, 6.25 mg t.i.d.) for migraine prevention were investigated in a randomized, double-blind, placebo-controlled, multicentre, parallel-group study. Patients (N = 170 intention-to-treat; MIG-99, N = 89; placebo, N = 81) suffering from migraine according to International Headache Society criteria were treated for 16 weeks after a 4-week baseline period. The primary endpoint was the average number of migraine attacks per 28 days during the treatment months 2 and 3 compared with baseline. Safety parameters included adverse events, laboratory parameters, vital signs and physical examination. The migraine frequency decreased from 4.76 by 1.9 attacks per month in the MIG-99 group and by 1.3 attacks in the placebo group (P = 0.0456). Logistic regression of responder rates showed an odds ratio of 3.4 in favour of MIG-99 (P = 0.0049). Adverse events possibly related to study medication were 9/107 (8.4%) with MIG-99 and 11/108 (10.2%) with placebo (P = 0.654). MIG-99 is effective and shows a favourable benefit-risk ratio.
Gelstat Migraine (sublingually administered feverfew and ginger compound) for acute treatment of migraine when administered during the mild pain phase.:Med Sci Monit. 2005 Sep;11(9):PI65-9. Epub 2005 Aug 26.Cady RK, Schreiber CP, Beach ME, Hart CC.Clinvest, Inc., Springfield and Headache Care Center, Springfield, Missouri, USA. rcady@primarycarenet.org
BACKGROUND: Treatment of migraine headaches is often delayed due to assessing the potential severity of an evolving headache or anticipating unwanted consequences from prescription medication. Studies have demonstrated improved pain-free response when prescription treatments are taken during the mild headache phase of a migraine. This study was designed to evaluate the efficacy of an OTC product, GelStat Migraine, when taken in the early, mild pain phase of migraine. MATERIAL/METHODS: An open-label study enrolling 30 subjects, male and female, with a one-year history of migraine meeting IHS diagnostic criteria with or without aura, 2-8 migraines per month and < or = 15 headache days per month. Inclusion required having migraines that consistently started at mild and worsened to moderate or severe, if untreated, in at least 75% of attacks. Subjects also had to be able to distinguish migraine from non-migraine headaches and reliably identify migraine early in the course of an attack. One headache was treated in the mild pain phase with GelStat Migraine, a combination of feverfew and ginger. RESULTS: 29 evaluable subjects completed the study, all treating at mild pain. Two hours after treatment, 48% were pain-free with 34% reporting a headache of only mild severity. 29% reported a recurrence within 24 hours. Side effects were minimal and not serious. 59% of subjects were satisfied with Gelstat Migraine therapy and 41% preferred GelStat Migraine or felt it was equal to their pre-study medication. CONCLUSIONS: GelStat Migraine is effective as a first line abortive treatment for migraine when initiated early during the mild headache phase.
Migraine and tension headache--a complementary and alternative medicine approach.:Aust Fam Physician. 2005 Aug;34(8):647-51. Review.Woolhouse M.
michellewoolhouse@hotmail.com
BACKGROUND: Migraine and tension headache are common--affecting up to 10% and 40% of the Australian population respectively--and result in significant reduction in social activities and work capacity for sufferers. OBJECTIVE: This article considers the evidence for the use of a range of complementary therapies and treatment in the prevention and management of both migraine and tension headache. DISCUSSION: Migraine and tension headache can have many precipitating factors. Considering dietary and environmental factors complements a migraine/headache consultation. There is evidence for the role of mind-body approaches, nutritional supplements such as riboflavin and magnesium, and acupuncture in the treatment of headache. By using a holistic approach we may be able to tailor a treatment program that is both effective and safe.
Parthenolide sensitizes ultraviolet (UV)-B-induced apoptosis via protein kinase C-dependent pathways.:Carcinogenesis. 2005 Dec;26(12):2149-56. Epub 2005 Jul 28.Won YK, Ong CN, Shen HM.Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
Parthenolide (PN) is the principal sesquiterpene lactone in feverfew (Tanacetum parthenium) with proven anti-inflammatory properties. We have previously reported that PN possesses strong anticancer activity in ultraviolet B (UVB)-induced skin cancer in SKH-1 hairless mice. In order to further understand the mechanism(s) involved in the anticancer activity of PN, we investigated the role of protein kinase C (PKC) in the sensitization activity of PN on UVB-induced apoptosis. Several subtypes of PKC have been reported to be involved in UVB-induced signaling cascade with both pro- and anti-apoptotic activities. Here we focused on two isoforms of PKC: novel PKCdelta and atypical PKCzeta. In JB6 murine epidermal cells, UVB induces the membrane translocations of both PKCs, and PN pre-treatment enhances the membrane translocation of PKCdelta, but inhibits the translocation of PKCzeta. Similar results were also detected when the activities of these PKCs were tested with the PKC kinase assay. Moreover, pre-treatment with a specific PKCdelta inhibitor, rotterlin, completely diminishes the sensitization effect of PN on UVB-induced apoptosis. When cells were transiently transfected with dominant negative PKCdelta or wild-type PKCzeta, the sensitization effect of PN on UVB-induced apoptosis was also drastically reduced. Further mechanistic study revealed that PKCzeta, but not PKCdelta, is required for UVB-induced p38 MAPK activation and PN is likely to act through PKCzeta to suppress p38 activation in UVB-treated JB6 cells. In conclusion, we demonstrated that PN sensitizes UVB-induced apoptosis via PKC-dependent pathways.
Parthenolide is the component of tanacetum parthenium that inhibits nitroglycerin-induced Fos activation: studies in an animal model of migraine.:Cephalalgia. 2005 Aug;25(8):612-21.Tassorelli C, Greco R, Morazzoni P, Riva A, Sandrini G, Nappi G.Laboratory of Pathophysiology of Integrative Autonomic Systems, IRCCS Neurological Institute C. Mondino Foundation and University Centre for the Study of Adaptive Disorder and Headache, Pavia, Italy. cristina.tassorelli@mondino.it
Tanacetum parthenium (TP) is a member of the Asteracee family long used empirically as a herbal remedy for migraine. So far, however, clinical trials have failed to prove consistently the effectiveness of TP extracts in preventing migraine attacks, probably as a consequence of the uncertainty as regards the active principle. In this study, the biological effects of different TP extracts and purified parthenolide were tested in an animal model of migraine based on the quantification of neuronal activation induced by nitroglycerin. The extract enriched in parthenolide significantly reduced nitroglycerin-induced Fos expression in the nucleus trigeminalis caudalis. Purified parthenolide inhibited nitroglycerin-induced neuronal activation in additional brain nuclei and, significantly, the activity of nuclear factor-kappaB. These findings strongly suggest that parthenolide is the component responsible for the biological activity of TP as regards its antimigraine effect and provide important information for future controlled clinical trials.
Herbs and nutrients in the treatment of depression, anxiety, insomnia, migraine, and obesity.:J Psychiatr Pract. 2001 Mar;7(2):75-91.Brown RP, Gerbarg PL.
Columbia University College of Physicians and Surgeons, USA.
Although a multitude of pharmaceutical agents are available for the treatment of mood disorders, anxiety and insomnia, many patients have difficulty tolerating the side effects, do not respond adequately, or eventually lose their response. Many therapeutic herbs and nutrients have far fewer side effects and may provide an alternative treatment or can be used to enhance the effect of prescription medications. In the article, the authors review the quality of the evidence supporting the clinical effects of a number of commonly used types of complementary/alternative medicine (CAM) for mood disorders, anxiety, and insomnia. They review data on the use of St. John's Wort, S-adenosyl-methionine (SAM-e), B vitamins, inositol, omega-3 fatty acids, and choline for mood disorders; data on the use of kava and other herbal agents and fish extract for anxiety and insomnia; and data on valerian and melatonin for insomnia. The authors also discuss the use of CAM to treat migraines, which may be comorbid with mood and anxiety disorders, and obesity, which can occur as a side effect of psychotropic medications. They consider the data on feverfew and butterbur for migraines and on chromium picolinate and the combination of ephedrine and caffeine for obesity. The authors also review issues related to comorbid medical illness, side effects, drug interactions, dosage, and brand selection.
Comparative effects of the herbal constituent parthenolide (Feverfew) on lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver.:J Inflamm (Lond). 2005 Jun 29;2:6.Smolinski AT, Pestka JJ.Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan, USA. alexa.smolinski@kellogg.co
BACKGROUND: Parthenolide, a major sesquiterpene lactone present in extracts of the herb Feverfew, has been investigated for its inhibitory effects on mediators of inflammation, including the proinflammatory cytokines. Although parthenolide's anti-inflammatory effects have been investigated in vitro, little in vivo data are available. Moreover, the molecular mechanisms for these inhibitory effects are not fully understood. The objective of this study was to test the hypothesis that parthenolide suppresses lipopolysaccharide (LPS)-induced serum (interleukin) IL-6, tumor necrosis factor (TNF)-alpha, IL-1beta and cyclooxygenase (COX)-2 expression in mice as indicated by reduced splenic and liver mRNA levels. METHODS: Mice were co-treated i.p. with LPS (1 mg/kg bw) and parthenolide (5 mg/kg bw) and blood, spleen and liver collected. Serum was analyzed for IL-6, TNF-alpha and IL-1beta by ELISA. Total RNA was extracted from spleen and liver, and real-time RT-PCR was used to determine relative mRNA expression of IL-1beta, IL-6, TNF-alpha and COX-2. RESULTS: LPS induced increases in serum IL-6 and TNF-alpha concentrations with only IL-6 being suppressed in parthenolide-treated mice. Induction of IL-6 mRNA was reduced, TNF-alpha and COX-2 mRNAs unchanged, and IL-1beta mRNA increased in spleens of parthenolide plus LPS co-treated animals compared to LPS-only. No significant differences were observed in inflammatory gene expression between these two groups in liver samples. Overall, mRNA expression of each proinflammatory gene was much higher in spleen when compared to liver. CONCLUSION: In summary, only one gene, IL-6, was modestly suppressed by parthenolide co-exposure which contrasts with many in vitro studies suggesting anti-inflammatory effects of this compound. Also, LPS evoked greater effects in spleen than liver on expression of proinflammatory genes. Further study of the effects of parthenolide and other herbal constituents on inflammatory gene expression using model animal systems as described here are critical to evaluating efficacy of such supplements as well as elucidating their mechanisms of action.
Parthenolide and abscisic acid synthesis in feverfew are associated but environmental factors affect them dissimilarly.:J Plant Physiol. 2005 May;162(5):485-94.Fonseca JM, Rushing JW, Rajapakse NC, Thomas RL, Riley MB.Department of Horticulture, Clemson University, Clemson, SC 29634-0375, USA. jfonseca@ag.arizona.edu
The effect of harvest time, shading prior to harvest and water stress on parthenolide (PRT) concentration in feverfew and its possible connection with the abscisic acid (ABA) pathway were investigated. In plants harvested at different times of the day, acetumar the PRT levels were highest during late afternoon while ABA levels were greatest during morning hours. Shading plants during the afternoon prior to harvest caused a two-fold increase in ABA and no significant difference in PRT levels. ABA was higher in water-stressed plants while PRTcontent increased in plants following recovery from a water stress event. ABA inhibitors, norflurazon, sodium tungstate, naproxen and sodium bisulfite, were used to determine the connection between the biosynthesis of PRTand ABA. Norflurazon and naproxen reduced PRT concentration in cut flowers and in 2-month old plants. Sodium bisulfite and sodium tungstate reduced PRT only in cut flowers. Application of 2,4-D, a promoter of ABA synthesis, to potted plants resulted in a 2.5 fold increase in PRT levels. The inhibition of PRT formation in response to ABA inhibitors and the increase in PRT concentration observed with 2,4-D application indicated that PRT is derived from carotenoid synthesis similarly to ABA and not directly from farnesyl pyrosphosphate (FPP) as suggested for other sesquiterpene Lactones. However, PRT and ABA levels are affected dissimilarly by environmental conditions. The overall results of the study indicated that simple agricultural practices, such as harvesting during afternoon and subjecting plants to a single water stress event, can increase PRT concentration in the final feverfew product with no additional costs of production prior to harvest.
Preventive treatment of headaches.:Curr Opin Neurol. 2005 Jun;18(3):289-92. Review.Silberstein SD.Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. Stephen.Silberstein@jefferson.edu
PURPOSE OF REVIEW: To review recent advances in preventive headache treatment. RECENT FINDINGS: Migraine may be a progressive disorder. Aggressive treatment may stop progression. Propranolol, the beta-blocker, and the anticonvulsant topiramate are effective for migraine prevention. Feverfew, montelukast and acupuncture have not proven effective. SUMMARY: New drugs and other treatment strategies expand the spectrum of preventive migraine treatments.
Parthenolide and sulindac cooperate to mediate growth suppression and inhibit the nuclear factor-kappa B pathway in pancreatic carcinoma cells.:Mol Cancer Ther. 2005 Apr;4(4):587-94.Yip-Schneider MT, Nakshatri H, Sweeney CJ, Marshall MS, Wiebke EA, Schmidt CM.Department of Surgery, Indiana University School of Medicine, Room 041, Building R4, 1044 West Walnut Street, Indianapolis, IN 46202, USA. myipschn@iupui.edu
Activation of the transcription factor nuclear factor-kappa B (NF-kappa B) has been implicated in pancreatic tumorigenesis. We evaluated the effect of a novel NF-kappa B inhibitor, parthenolide, a sesquiterpene lactone isolated from the herb feverfew, in three human pancreatic tumor cell lines (BxPC-3, PANC-1, and MIA PaCa-2). Parthenolide inhibited pancreatic cancer cell growth in a dose-dependent manner with substantial growth inhibition observed between 5 and 10 micromol/L parthenolide in all three cell lines. Parthenolide treatment also dose-dependently increased the amount of the NF-kappa B inhibitory protein, I kappa B-alpha, and decreased NF-kappa B DNA binding activity. We have previously shown that nonsteroidal anti-inflammatory drugs (NSAID) suppress the growth of pancreatic cancer cells. To determine whether inhibition of the NF-kappa B pathway by parthenolide could sensitize pancreatic cancer cells to NSAID inhibition, BxPC-3, PANC-1, and MIA PaCa-2 cells were treated with parthenolide and the NSAID sulindac, either alone or in combination. Treatment with the combination of parthenolide and sulindac inhibited cell growth synergistically in MIA PaCa-2 and BxPC-3 cells and additively in PANC-1 cells. In addition, treatment with the parthenolide/sulindac combination lowered the threshold for apoptosis. Increased levels of I kappa B-alpha protein were detected, especially in MIA PaCa-2 cells, after treatment with parthenolide and sulindac compared with each agent alone. Similarly, decreased NF-kappa B DNA binding and transcriptional activities were detected in cells treated with the combination compared with the single agents, demonstrating cooperative targeting of the NF-kappa B pathway. These data provide preclinical support for a combined chemotherapeutic approach with NF-kappa B inhibitors and NSAIDs for the treatment of pancreatic adenocarcinoma.
Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium.:Antimicrob Agents Chemother. 2005 Jan;49(1):176-82.Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, Dias Filho BP, Morgado-D¨ªaz JA, de Souza W, Nakamura CV.Departamento de An¨¢lises Cl¨ªnicas, Universidade Estadual de Maring¨¢, Bloco I-90 Sala 123 CCS, Av. Colombo 5790, BR-87020-900, Maring¨¢, Paran¨¢, Brazil.
The in vitro activity of parthenolide against Leishmania amazonensis was investigated. Parthenolide is a sesquiterpene lactone purified from the hydroalcoholic extract of aerial parts of Tanacetum parthenium. This isolated compound was identified through spectral analyses by UV, infrared, (1)H and (13)C nuclear magnetic resonance imaging, DEPT (distortionless enhancement by polarization transfer), COSY (correlated spectroscopy), HMQC (heteronuclear multiple-quantum coherence), and electron spray ionization-mass spectrometry. Parthenolide showed significant activity against the promastigote form of L. amazonensis, with 50% inhibition of cell growth at a concentration of 0.37 microg/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 microg/ml. The purified compound showed no cytotoxic effects against J774G8 macrophages in culture and did not cause lysis in sheep blood when it was used at higher concentrations that inhibited promastigote forms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with gelatin as the substrate showed that the enzymatic activity of the enzyme cysteine protease increased following treatment of the promastigotes with the isolated compound. This finding was correlated with marked morphological changes induced by parthenolide, such as the appearance of structures similar to large lysosomes and intense exocytic activity in the region of the flagellar pocket, as seen by electron microscopy. These results provide new perspectives on the development of novel drugs with leishmanicidal activities obtained from natural products.
Microtubule-interfering activity of parthenolide:Chem Biol Interact. 2004 Oct 15;149(2-3):165-73.Miglietta A, Bozzo F, Gabriel L, Bocca C.Department of Experimental Medicine and Oncology, University of Torino, Corso Raffaello 30, 10125 Torino, Italy. antonella.miglietta@unito.it
Parthenolide is an active sesquiterpene lactone present in a variety of medicinal herbs, well known as anti-inflammatory drug. It has recently been proposed as a chemotherapeutic drug, but the pharmacological pathways of its action have not yet been fully elucidated. Firstly, we explored whether the anticancer properties of parthenolide may be related to a tubulin/microtubule-interfering activity. We additionally compared bioactivities of parthenolide with those checked after combined treatments with paclitaxel in human breast cancer MCF-7 cells. Parthenolide exerted in vitro stimulatory activity on tubulin assembly, by inducing the formation of well-organized microtubule polymers. Light microscopy detections showed that parthenolide-induced alterations of either microtubule network and nuclear morphology happened only after combined exposures to paclitaxel. In addition, the growth of MCF-7 cells was significantly inhibited by parthenolide, which enhanced paclitaxel effectiveness. In conclusion, the antimicrotubular and antiproliferative effects of parthenolide, well known microtubule-stabilizing anticancer agent, may influence paclitaxel activity. The tubulin/microtubule system may represent a novel molecular target for parthenolide, to be utilized in developing new combinational anticancer strategies.
A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial:Headache. 2004 Oct;44(9):885-90.Maizels M, Blumenfeld A, Burchette R.Kaiser Permanente, Family Practice, Woodland Hills, CA, USA.
OBJECTIVE: To determine the efficacy for migraine prophylaxis of a compound containing a combination of riboflavin, magnesium, and feverfew. BACKGROUND: Previous studies of magnesium and feverfew for migraine prophylaxis have found conflicting results, and there has been only a single placebo-controlled trial of riboflavin. DESIGN/METHODS: Randomized double-blind placebo-controlled trial of a compound providing a daily dose of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo contained 25 mg riboflavin. The study included a 1-month run-in phase and 3-month trial. The protocol allowed for 120 patients to be randomized, with a preplanned interim analysis of the data after 48 patients had completed the trial. RESULTS: Forty-nine patients completed the 3-month trial. For the primary outcome measure, a 50% or greater reduction in migraines, there was no difference between active and "placebo" groups, achieved by 10 (42%) and 11 (44%), respectively (P=.87). Similarly, there was no significant difference in secondary outcome measures, for active versus placebo groups, respectively: 50% or greater reduction in migraine days (33% and 40%, P=.63); or change in mean number of migraines, migraine days, migraine index, or triptan doses. Compared to baseline, however, both groups showed a significant reduction in number of migraines, migraine days, and migraine index. This effect exceeds that reported for placebo agents in previous migraine trials. CONCLUSION: Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis, and suggests that riboflavin 25 mg may be an active comparator. There is at present conflicting scientific evidence with regard to the efficacy of these compounds for migraine prophylaxis.
Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction.:Rapid Commun Mass Spectrom. 2004;18(19):2273-81.Unger M, Frank A.Institute of Pharmacy and Food Chemistry, Julius Maximilians-University W¨¹rzburg, 97074 W¨¹rzburg, Germany. m.unger@pzlc.uni-wuerzburg.de
Here we describe a liquid chromatography/mass spectrometry (LC/MS) method with automated online extraction (LC/LC/MS) to simultaneously determine the in vitro inhibitory potency of herbal extracts on six major human drug-metabolising cytochrome P450 enzymes. Substrates were incubated with a commercially available mixture of CYP1A2/2C8/2C9/2C19/2D6 and 3A4 from baculovirus-infected insect cells and the resulting metabolites were quantified with LC/LC/MS using electrospray ionisation in the selected ion monitoring mode. Consistent inhibitory activities were obtained for known inhibitors and plant extracts using the enzyme/substrate cocktail and the individual enzymes/substrates. Popular herbal remedies including devil's claw root (Harpagophytum procumbens), feverfew herb (Tanacetum parthenium), fo-ti root (Polygonum multiflorum), kava-kava root (Piper methysticum), peppermint oil (Mentha piperita), eucalyptus oil (Eucalyptus globulus), red clover blossom (Trifolium pratense) and grapefruit juice (GJ; Citrus paradisi) could be identified as inhibitors of the applied CYP enzymes with IC(50) values between 20 and 1000 microg/mL.
Evidenced-based use of botanicals, minerals, and vitamins in the prophylactic treatment of migraines.:J Am Acad Nurse Pract. 2004 Jun;16(6):251-6. Review.Rios J, Passe MM.University of Texas at Austin School of Nursing, USA. janie_rios01@yahoo.com
PURPOSE: To analyze evidence-based information about alternative prophylactic pharmacological migraine treatments utilizing feverfew, butter-bur, magnesium, and riboflavin and to discuss the mechanism of action, dosage recommendations, side effects, and contraindications for each treatment. DATA SOURCES: Data obtained via electronic databases and professional medical references. CONCLUSIONS: Current clinical data support the use of fever-few, butterbur, magnesium, and riboflavin in migraine prophylaxis; however, studies are limited but promising regarding the participants' perceived relief. Studies with rigorous methodologies and larger sample sizes are needed to further support the safe and effective use of these treatments. IMPLICATIONS FOR PRACTICE: With increased patient access to information regarding alternative migraine treatments, nurse practitioners (NPs) and other health care providers must be knowledgeable about evidence-based data regarding these alternative treatments to appropriately offer safe patient care.
Involvement of proapoptotic Bcl-2 family members in parthenolide-induced mitochondrial dysfunction and apoptosis.:Cancer Lett. 2004 Aug 10;211(2):175-88.Zhang S, Ong CN, Shen HM.Department of Community, Occupational and Family Medicine, Faculty of Medicine (MD3), National University of Singapore, 16 Medical Drive, Singapore 117597.
Parthenolide is a sesquiterpene lactone responsible for the bioactivities of Feverfew. Besides its potent anti-inflammatory effect, this compound has recently been reported to induce apoptosis in cancer cells, possibly through mitochondrial dysfunction. In the present study, we attempted to examine parthenolide-mediated cell death signaling pathway by focusing on the involvement of Bcl-2 family members. Using a human colorectal cancer cell line COLO205, we first demonstrated that parthenolide acted through the cell death receptor pathway to activate caspase 8. Following caspase 8 activation, Bid, a proapoptotic Bcl-2 member, was cleaved and this cleavage then triggered Bax conformational changes and Bax translocation from cytosol to mitochondrial membrane. Meanwhile, another proapoptotic protein, Bak, was up-regulated and oligomerized on the mitochondrial membrane. All these alterations were found to be prerequisite for the subsequent release of proapopototic mitochondrial proteins, including cytochrome c and Samc, in parthenolide-treated cells. Moreover, selective inhibition of caspase 8 activity by a synthetic caspase inhibitor (IETD-FMK) or overexpression of a viral protein (CrmA) suppressed the cleavage of Bid, conformational changes of Bax, cytochrome c release, and apoptosis. Therefore, the proapoptotic Bcl-2 family members are important mediators relaying the cell death signaling elicited by parthenolide from caspase 8 to downstream effector caspases such as caspase 3, and eventually to cell death.
Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells.:Cancer Lett. 2004 May 28;208(2):143-53.Zhang S, Ong CN, Shen HM.Department of Community, Occupational and Family Medicine, Faculty of Medicine (MD3), National University of Singapore, 16 Medical Drive, Singapore 117597.
Parthenolide is one of the main components responsible for the anti-inflammatory property of Feverfew. Recently, parthenolide has shown to induce apoptosis in cancer cells. Here we further studied the mechanism of parthenolide-induced apoptosis by focusing on the role of intracellular thiols and calcium in a human colorectal cancer cell, COLO 205. Parthenolide rapidly depleted intracellular thiols, including both free glutathione (GSH) and protein thiols. Concomitantly, there were dose- and time-dependent increases in intracellular reactive oxygen species (ROS) and calcium levels. Increased expression of GRP78 protein, a marker for endoplasmic reticulum stress was also detected. All these changes preceded parthenolide-induced apoptotic cell death. More importantly, pretreatment with N-acetylcysteine, a precursor of GSH synthesis, protected the cells from parthenolide-induced thiol depletion, ROS production, cytosolic calcium increase and completely blocked parthenolide-induced apoptosis. On the contrary, pretreatment of buthionine sulfoximine, an inhibitor of GSH synthesis sensitized the cell to apoptosis. These data clearly demonstrate that the intracellular thiols and calcium equilibrium play a critical role in parthenolide-induced apoptotic cell death.
Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer:Invest New Drugs. 2004 Aug;22(3):299-305.Curry EA 3rd, Murry DJ, Yoder C, Fife K, Armstrong V, Nakshatri H, O'Connell M, Sweeney CJ.Department of Pharmacy Practice, Purdue University, Indianapolis, IN, USA.
PURPOSE: Feverfew is a botanical product that contains parthenolide. Parthenolide has in vitro and in vivo anti-tumor and anti-angiogenic activity. Feverfew has been used extensively without any formal pharmacokinetic analysis. A Phase I trial was conducted to evaluate the pharmacokinetics and toxicity of parthenolide given as a component of "feverfew." PATIENTS AND METHODS: Feverfew (Tanacet trade mark ) was administered as a daily oral tablet in a 28-day cycle. A starting dose of 1 mg per day was explored with subsequent dose escalations to 2, 3, and 4 mg. Assessment of plasma pharmacokinetics was performed on patients accrued to the trial. Solid phase extraction and mass spectroscopy were used to evaluate parthenolide plasma concentrations. The limit of detection for parthenolide in plasma was 0.5 ng/ml. Patients were evaluated for response after every two cycles. RESULTS: Feverfew given on this schedule had no significant toxicity, and the maximum tolerated dose was not reached. When parthenolide was administered at doses up to 4 mg as a daily oral capsule in the feverfew preparation, there was not detectable concentration in the plasma. Because of this, parthenolide pharmacokinetics were not able to be completed. CONCLUSION: Feverfew, with up to 4 mg of parthenolide, given daily as an oral tablet is well tolerated without dose-limiting toxicity, but does not provide detectable plasma concentrations. Purification of parthenolide for administration of higher doses will be needed.
Chemopreventive activity of parthenolide against UVB-induced skin cancer and its mechanisms.:Carcinogenesis. 2004 Aug;25(8):1449-58. Epub 2004 Mar 19.Won YK, Ong CN, Shi X, Shen HM.Department of Community, Occupational, and Family Medicine, Faculty of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117597, Republic of Singapore.
Parthenolide (PN) is a major sesquiterpene lactone of feverfew (Tanacetum parthanium) with known anti-inflammatory activity. However, the anticancer effects of PN have not been well studied. In the present investigation, we examined the cancer chemopreventive property of PN using a combination of in vivo and in vitro approaches. We first tested the anticancer effect of PN in UVB-induced skin cancer model. Mice fed with PN (1 mg/day) showed a delayed onset of papilloma incidence, a significant reduction in papilloma multiplicity (papilloma/mouse) and sizes when compared with the UVB-only group. To our surprise, neither PN nor the known cyclooxygenase (COX)-2 inhibitor celecoxib inhibit UVB-induced COX-2 expression and epidermal prostaglandin E2 (PGE2) production. We next investigated the molecular mechanism(s) involved in its anticancer effects using cultured JB6 murine epidermal cells. Non-cytotoxic concentrations of PN significantly inhibited UVB-induced activator protein-1 DNA binding and transcriptional activity. In addition, PN pre-treatment also inhibited c-Jun-N-terminal kinase (JNK) and p38 kinase activation. More importantly, we found that impaired AP-1, JNK and p38 signaling led to the sensitization of JB6 cells to UVB-induced apoptosis. Data from our study for the first time confirm the anticancer property of PN in an animal model, and provide evidence that the inhibitory effects on AP-1 and mitogen-activated protein kinases serve as one of the underlying mechanisms for the cancer chemopreventive property of PN.
Feverfew for preventing migraine.:Cochrane Database Syst Rev. 2004;(1):CD002286. Review.Pittler MH, Ernst E.Department of Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter, Devon, UK, EX2 4NT.
BACKGROUND: Feverfew (Tanacetum parthenium L.) extract is a herbal remedy used for preventing attacks of migraine. OBJECTIVES: To systematically review the evidence from double-blind randomised controlled trials (RCTs) assessing the clinical efficacy and safety of feverfew versus placebo for preventing migraine. SEARCH STRATEGY: Publications describing (or which might describe) double-blind RCTs of feverfew extract for migraine were sought through the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2003); PREMEDLINE/MEDLINE (1966 to July 2003); EMBASE (1974 to July 2003); the trials register of the Cochrane Pain, Palliative and Supportive care group (July 2003); and AMED (1985 to July 2003). Manufacturers of feverfew were contacted and the bibliographies of identified articles checked for further trials. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew for preventing migraine were included. Trials using clinical outcome measures were included. Trials focusing exclusively on physiological parameters were excluded. There were no restrictions regarding the language of publication. DATA COLLECTION AND ANALYSIS: Data on patients, interventions, methods, outcome measures, results and adverse events were extracted systematically. Methodological quality was evaluated using the scoring system developed by Jadad and colleagues. Two reviewers independently selected studies, assessed methodological quality and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. MAIN RESULTS: Five trials (343 patients) met the inclusion criteria. Results from these trials were mixed and did not convincingly establish that feverfew is efficacious for preventing migraine. Only mild and transient adverse events were reported in the included trials. REVIEWER'S CONCLUSIONS: There is insufficient evidence from randomised, double-blind trials to suggest an effect of feverfew over and above placebo for preventing migraine. It appears from the data reviewed that feverfew presents no major safety problems.
Transport of parthenolide across human intestinal cells (Caco-2).:Planta Med. 2003 Nov;69(11):1009-12.Khan SI, Abourashed EA, Khan IA, Walker LA.
National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. skhan@olemiss.edu
This study examined the intestinal epithelial membrane transport of the sesquiterpene lactone parthenolide, a bioactive compound present in the migraine prophylactic herb feverfew. The Caco-2 human colonic cell line was used as an in vitro model of the human intestinal mucosal barrier. The bidirectional transport (apical to basolateral and basolateral to apical) of parthenolide was investigated using Caco-2 monolayers grown on Transwell inserts. Quantitation of parthenolide was performed using high performance liquid chromatography (HPLC). Apical to basolateral and basolateral to apical permeability coefficients and percent transport were calculated and a potential bioavailability of parthenolide was determined. Sodium fluorescein was used as a marker for paracellular leakage. Parthenolide, at a concentration of 250 microM, demonstrated substantial linear transport across the monolayer. The transport parameters were not affected by the presence of MK-571, an inhibitor of multidrug resistance transporter P-glycoprotein (MRP). Upon comparison of the transport parameters of parthenolide with atenolol under identical conditions and the reported values for model compounds like mannitol and propranolol, it is concluded that parthenolide is effectively absorbed through the intestinal mucosa via a passive diffusion mechanism.
Bioactive flavonoids of Tanacetum parthenium revisited.:Phytochemistry. 2003 Sep;64(2):567-9.Long C, Sauleau P, David B, Lavaud C, Cassabois V, Ausseil F, Massiot G.UMR CNRS 1973, Institut de Recherche Pierre Fabre, 3 rue Ariane, 31527 Ramonville, France.
Bio-guided fractionation of an extract from Tanacetum parthenium showing activity as mitotic blocker allowed the isolation and identification of santin 3, jaceidin 2 and centaureidin 1. The latter two closely related flavonols, which, to the best of our knowledge, are isolated here together for the first time, form a mixture difficult to resolve and which is probably the reason for the confusion in the literature regarding their occurrence. Centaureidin 1 had an IC50 of 1 microM while jaceidin 2 and santin 3 were 200 times less active.
Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew).:Food Chem Toxicol. 2003 Oct;41(10):1381-90.Smolinski AT, Pestka JJ.Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224, USA.
Dietary supplements are not subject to the same pre-market approval as conventional drugs, thus the true efficacy and, in cases, safety of these products is not known. The objective of this study was to evaluate the potential anti-inflammatory properties of three herbal constituents, apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew) on lipopolysaccaharide (LPS)-induced proinflammatory cytokine production, and to determine if effects in cell culture could predict results in an intact animal model. Murine macrophage cells and mice were treated with the stimulant LPS and herbal constituents, and resultant culture supernatant and serum, respectively, were evaluated for interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha by ELISA. All three constituents inhibited LPS-induced IL-6 and/or TNF-alpha production in culture. Inhibition of these two cytokines was observed in mice, but did not display the same patterns of inhibition as cell culture data. The results suggest that all three constituents possessed anti-inflammatory properties, but that cell culture data can only be used to approximate potential effects in animals, and must be confirmed using appropriate animal models.
The anti-inflammatory sesquiterpene lactone parthenolide suppresses IL-4 gene expression in peripheral blood T:Eur J Immunol. 2002 Dec;32(12):3587-97.Li-Weber M, Giaisi M, Treiber MK, Krammer PH.Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany. m.li-weber@dkfz-heidelberg.de
Sesquiterpene lactones (SL) derived from Mexican India medicinal plants and parthenolide, the major SL from European feverfew, have raised considerable interest because of their anti-inflammatory and complex pharmacological action. Interleukin-4 (IL-4) is a key cytokine that influences the development of T helper 2 cells and plays an important role in the pathogenesis of allergic diseases. We show here that the anti-inflammatory parthenolide suppresses IL-4 expression at the mRNA and the protein levels in a dose-dependent manner. We demonstrate that parthenolide blocks NF-kappaB binding to two important IL-4 promoter regulatory elements and suppresses promoter activity upon T cell activation. Differences regarding the effects of parthenolide on expression levels of IL-4, IL-2 and IFN-gamma were observed. Parthenolide (2.5 microM) could completely suppress IL-4 protein levels secreted in anti-CD3/CD28-stimulated peripheral blood T cells from allergic and normal donors. Complete inhibition of IL-2 and IFN-gamma requires higher doses of parthenolide. So far, drugs directed against IL-4 expression have not been described. This finding raises the potential to develop parthenolide to treat IL-4-mediated allergic-like inflammation.
Migraine: preventive treatment.:Curr Med Res Opin. 2001;17 Suppl 1:s87-93. Review.Silberstein SD.Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA, USA. stephen.silberstein@mail.tju.edu
Preventive treatment is designed to decrease headache frequency. It should be used if headaches are too frequent, disabling, or associated with worrisome neurological features or if acute treatment is overused or ineffective. The chosen drug should be given an adequate trial in the absence of interfering medications. Choose a drug based on its efficacy, adverse event profile, and the presence of coexistent conditions.
The anti-inflammatory sesquiterpene lactone parthenolide suppresses CD95-mediated activation-induced-cell-death in T-cells.:Cell Death Differ. 2002 Nov;9(11):1256-65.Li-Weber M, Giaisi M, Baumann S, Treiber MK, Krammer PH.Tumorimmunology Program, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. m.li-weber@dkfz-heidelberg.de
Apoptosis is a morphologically distinct form of cell death involved in many physiological and pathological processes. The death receptor CD95 (APO-1/Fas) and its ligand (L) CD95L are critically involved in activation-induced-cell-death (AICD) of activated T-cells. Here we show that the anti-inflammatory sesquiterpene lactone parthenolide derived from the European traditional herb-medicine feverfew and many Mexican India medicinal plants suppresses expression of the CD95L and CD95 at the mRNA levels, thus, preventing T-cells from AICD. We demonstrate that parthenolide blocks NF-kappaB binding to the two NF-kappa binding sites of the CD95L promoter and suppresses promoter activity upon T-cell activation. Aberrant expression of CD95 and, particularly CD95L is dangerous and may lead to severe diseases. Our study indicates that parthenolide supports T-cell survival by down-regulating the CD95 system, at least in part, and, therefore, may have therapeutic potential as a new anti-apoptotic substance against AICD in T-cells.
The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind, multicentre, randomized placebo-controlled dose-response study.:Cephalalgia. 2002 Sep;22(7):523-32.Pfaffenrath V, Diener HC, Fischer M, Friede M, Henneicke-von Zepelin HH; Investigators.Munich, Department of Neurology, University of Essen, Essen. Germany. Vpfa@aol.com
Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic treatment of migraine. The primary objective was to show a dose-response of a new stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from feverfew (T. parthenium). Furthermore, the study should provide data on the safety and tolerability of MIG-99. In a randomized, double-blind, multicentre, controlled trial with an adaptive design, the clinical efficacy and safety of three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients (n = 147) suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients (n = 49) with at least four migraine attacks during the baseline period decreased in a dose-dependent manner (P = 0.001). The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.
Do monoterpenes released from feverfew (Tanacetum parthenium) plants cause airborne Compositae dermatitis?:Contact Dermatitis. 2002 Jul;47(1):14-8. Erratum in: Contact Dermatitis. 2003 Mar;48(3):179-80.Paulsen E, Christensen LP, Andersen KE.Department of Dermatology, Odense University Hospital, Odense, Denmark.
The Compositae plant feverfew (Tanacetum parthenium) is an important sensitizer in Europe and has been suspected of causing airborne Compositae dermatitis. A previous investigation of substances emitted from feverfew plants detected no sesquiterpene lactones, however, but mainly monoterpenes. The aims of this study were to test whether feverfew-allergic patients were also sensitive to some of the above-mentioned monoterpenes and, if so, to study associations between sensitization patterns, relevance of feverfew allergy and clinical features. 17 patients with + +/+ + + reactions to feverfew and parthenolide were tested with 15 selected monoterpenes and 2 sesquiterpenes. Of the 17 persons, 13 had positive and/or doubtful positive reactions to 1 or more monoterpenes. Only 1 person was allergic to several monoterpenes. Her history of gradually worsening Compositae dermatitis culminating in a probable airborne dermatitis, mimicking photosensitivity, and the disappearance of symptoms upon removal of feverfew plants suggest monoterpenes as a possible contributing factor. Similar associations between doubtful positive monoterpene reactions and clinical patterns, fragrance/colophonium allergy and relevance of feverfew allergy were not established with certainty. In conclusion, sensitization to the sesquiterpene lactones of feverfew is not invariably accompanied by sensitization to its volatile monoterpenes. The presence of monoterpene allergy, however, may contribute to airborne Compositae dermatitis.
Variations in parthenolide content and daily dose of feverfew products:Am J Health Syst Pharm. 2002 Aug 15;59(16):1527-31.Nelson MH, Cobb SE, Shelton J.
School of Pharmacy, Southwestern Oklahoma State University, 100 Campus Drive, Weatherford, OK 73096, USA. nelsonm@swosu.edu
Variations in the parthenolide content of feverfew products available to consumers were studied. Feverfew products were analyzed for the content of parthenolide, the purported active component. The actual weight of feverfew was determined only in those products containing dried feverfew leaf. The total daily doses of feverfew leaf and parthenolide were calculated by using the instructions on each product label. Parthenolide content was determined by high-performance liquid chromatography. The quantity of feverfew leaf in each capsule was similar to that stated on the label and ranged from 25 to 500 mg. Parthenolide content per dosage form varied 150-fold (from 0.02 to 3.0 mg), while percent parthenolide varied 5.3-fold (from 0.14% to 0.74%). If a person consumed the daily dose recommended on the label, intake of dried feverfew leaf would range from 225 to 2246 mg/day, a 10-fold variation, while intake of parthenolide would range from 0.06 to 9.7 mg/day, a 160-fold variation. Large variations were observed in the parthenolide contents and daily intake as recommended by the labeling in commercial feverfew products.
5-Hydroxytryptamine-inhibiting property of Feverfew: role of parthenolide content.:Acta Pharmacol Sin. 2000 Dec;21(12):1106-14.Mittra S, Datta A, Singh SK, Singh A.Panacea Biotec Limited, P O Lalru 140501, Punjab, India.
AIM: To study the mechanism of antimigraine activity of Tanacetum parthenium (Feverfew), its extracts and parthenolide, a component of Feverfew, by observing their effect on 5-HT storage and release, and stimulation of 5-HT2B and 5-HT2A receptors. Also to standardize a dosage form of Feverfew with respect to its parthenolide content. METHODS: Isometric responses to 5-HT and an indirect acting serotonergic, d-fenfluramine, were obtained on rat fundus and ileum. In one set of experiments the effect of dichloromethane extract of Feverfew and parthenolide was observed on the above. The extract was then thermally degraded upto 10%, 23%, and 33% with respect to its parthenolide content by keeping at 60 degrees C and 75% relative humidity and the experiments were repeated. In another set of experiments rats were fed with 20 mg/kg Feverfew powder (equivalent to a human dose of 500 micrograms parthenolide per day) for 30 d or were i.p. injected with parthenolide (23.4 micrograms/day) for 7 d. In the same set of experiments one group of rats were fed with 15% and 77% degraded Feverfew powder in the same dose as mentioned above. After 30 days the effects of the above were observed on 5-HT and d-fenfluramine. Feverfew was specially formulated and tested for stability under accelerated conditions. RESULTS: Parthenolide (1 x 10(-5) mol/L) non-competitively antagonised the effects of d-fenfluramine but had no significant effect on 5-HT2B and 5-HT2A receptors in rat fundus and ileum at 30 min which turned significant on increasing the incubation time to 1.5 h, in rat fundus. Parthenolide (5 x 10(-5) mol/L) followed the same trend. However, Feverfew extract (1 x 10(-5) mol/L) potently and directly blocked 5-HT2B and 5-HT2A receptors and neuronally released 5-HT. At 5 x 10(-5) mol/L the extract potently and irreversibly blocked the above. Both parthenolide and Feverfew extract showed a time-dependency in their action. The extract when degraded thermally upto 10% could significantly block the 5-HT receptors and neuronal release of 5-HT, however, on further degradation it lost its inhibitory capacity markedly. Similar results were observed in rats fed orally with undergraded and degraded Feverfew powder and injected i.p. with parthenolide. Feverfew powder was more effective than any of its extracts or pure parthenolide. CONCLUSION: Feverfew powder is more potent than any of its extract or parthenolide alone in its antiserotonergic activity. Degraded Feverfew extracts show a marked decrease in their antiserotonergic activity. With thermally degraded Feverfew powder containing less contents of parthenolide no built-up antiserotonergic responses were observed after one month. This ascertains that Feverfew should be dispensed in a properly stabilized form wherein its parthenolide content is not degraded to less than 90% of the original content.
Alternative therapies in headache. Is there a role?:Med Clin North Am. 2001 Jul;85(4):1077-84. Review.Mauskop A.New York Headache Center, New York, USA.
Alternative or complementary modes of treatment often lack scientific proof of efficacy. This is true for many drugs that are used for prophylaxis of headaches as well. Many of these complementary modes are inexpensive, harmless, and possibly effective. Patients can be given a list of options in the following order of clinician preference: aerobic exercise; isometric neck exercise; biofeedback; a combination product containing magnesium, riboflavin, and feverfew; and acupuncture. The patient must decide which of these approaches is appealing, affordable, and realistically doable.
Pesticidal properties of parthenin (from Parthenium hysterophorus) and related compounds.:Pest Manag Sci. 2001 Jan;57(1):95-101.Datta S, Saxena DB.
Division of Agricultural Chemicals, Indian Agricultural Research Institute, New Delhi-110 012, India.
Eleven sesquiterpene lactone derivatives of parthenin (1), obtained from wild feverfew, Parthenium hysterophorus, were prepared by chemical and photochemical transformations. The compounds tested were a pyrazoline adduct (2) of parthenin, its cyclopropyl (3) and propenyl (4) derivatives, anhydroparthenin (5), a dihydro-deoxygenated product (6), a formate (7) and its corresponding alcohol (8) and acetate (9), a rearranged product (10), lactone (11) and hemiacetal (12). All these derivatives, along with parthenin, were tried for their antifeedant action against sixth-instar larvae of Spodoptera litura, for insecticidal activity against the adults of store grain pest Callosobruchus maculatus, for phytotoxic activity against Cassia tora, and for nematicidal activity against the juvenile stage-II (J2) of the root knot nematode Meloidogyne incognita. Antifeedent bioassay revealed that parthenin is moderately antifeedant. Among the derivatives, the saturated lactone (11) was found to be about 2.25 times more active than parthenin. The pyrazoline adduct (2) was found to be the most effective as an insecticide, with LC50 values after 24, 48 and 72 h of 96, 43 and 32 mg litre-1, respectively, which are comparable with neem extract. Compound 4 was found to be the most effective inhibitor of germination and seedling growth of C tora, with ID50 values for germination, plumule length and radicle length of 136, 326 and 172 compared with 364, 738 and 427 mg litre-1, respectively, for parthenin. Compound 10 was found to be the most effective in terms of nematicidal activity. The LC50 values for this compound were 273 and 104 mg litre-1, respectively, after 48 and 72 h compared with 862 and 512 mg litre-1 observed for parthenin after 48 and 72 h.
The efficacy and safety of feverfew (Tanacetum parthenium L.): an update of a systematic review.:Public Health Nutr. 2000 Dec;3(4A):509-14. Review.Ernst E, Pittler MH.Department of Complementary Medicine, School of Postgraduate Medicine and Health Science, University of Exeter, UK. e.ernst@exeter.ac.uk
OBJECTIVE: Feverfew (Tanacetum parthenium L.) is a popular herbal remedy often advocated for the prevention of migraine. The aims of this systematic review are to update the evidence from rigorous clinical trials for or against the efficacy of feverfew for migraine prevention and to provide a safety profile of this herbal remedy. DESIGN: Literature searches were performed using the following databases: Medline, Embase, Biosis, CISCOM and the Cochrane Library (all from their inception to December 1999). Only randomized, placebo-controlled, double-blind trials of feverfew mono-preparations for the prevention of migraine in human subjects were included. All articles were read by two independent reviewers. Data were extracted in a pre-defined, standardized fashion. The methodological quality of the trials was evaluated by the Jadad score. For the assessment of safety issues, major reference texts were also consulted. RESULTS: Six trials met the inclusion/exclusion criteria. The majority favour feverfew over placebo. Yet important caveats exist. The data also suggest that feverfew is associated with only mild and transient adverse effects and few other safety concerns. CONCLUSIONS: Feverfew is likely to be effective in the prevention of migraine. There are no major safety problems.
Determination of parthenolide in selected feverfew products by liquid chromatography.:J AOAC Int. 2000 Jul-Aug;83(4):789-92.Abourashed EA, Khan IA, Abourashed EA, Khan IA.University of Mississippi, School of Pharmacy, National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, and Department of Pharmacognosy, University 38677, USA.
The migraine prophylactic herb feverfew (Tanacetum parthenium L.) is marketed in the United States in a variety of forms and compositions. Although its therapeutic efficacy is still uncertain, the sesquiterpene lactone parthenolide is the constituent recommended to be measured for quality control of feverfew preparations. A validated liquid chromatographic method was developed and used to estimate parthenolide in a number of U.S. feverfew market products formulated as capsules, tablets, or crude powder. The method uses a Lichrosphere 5 C18 column, a mobile phase consisting of 50 mM NaH2PO4 in H2O (solvent A), and CH3CN-MeOH (90 + 10, v/v; solvent B). Elution was run at a flow rate of 1.0 mL/min with a linear gradient of 50-15% A in B over 20 min and UV detection at 210 nm. The correlation coefficient for the calibration curve was 0.9999 over the range of 0.00-0.400 mg/mL. Overall recovery of parthenolide was 103.1%.
Feverfew for preventing migraine.:Cochrane Database Syst Rev. 2000;(3):CD002286. Review. Update in: Cochrane Database Syst Rev. 2004;(1):CD002286.Pittler MH, Vogler BK, Ernst E.Department of Complementary Medicine, School of Postgraduate Medicine & Health Sciences, University of Exeter, United Kingdom, 25 Victoria Park Road, Exeter, Devon, UK, EX2 4NT. M.H.Pittler@exeter.ac.uk
BACKGROUND: Feverfew (Tanacetum parthenium L.) is a popular herbal remedy for migraine. OBJECTIVES: To systematically review the evidence for or against the efficacy of feverfew versus placebo for the prevention of migraine. SEARCH STRATEGY: Electronic literature searches were performed using the databases CISCOM (Research Council for Complementary Medicine, London, UK), MEDLINE, EMBASE, Biosis and the Cochrane Library (each from its inception to April 1998). Manufacturers were contacted and the bibliographies of identified articles checked for further trials. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew for preventing migraine were included. No restrictions regarding the language of publication were imposed. DATA COLLECTION AND ANALYSIS: Data on patients, interventions, methods, outcomes and results were extracted in a pre-defined, standardised manner. Methodological quality was evaluated using the scoring system developed by Jadad and colleagues. Both data extraction and the assessment of methodological quality were performed independently by two reviewers. MAIN RESULTS: Four trials met the inclusion criteria. The majority of these trials suggested beneficial effects of feverfew compared with placebo. However, the trial with the highest methodological quality, which was also among the largest, found no significant difference between feverfew and placebo. REVIEWER'S CONCLUSIONS: The efficacy of feverfew for the prevention of migraine has not been established beyond reasonable doubt.
Feverfew as a prophylactic treatment of migraine:Neurol Neurochir Pol. 1999;33 Suppl 5:89-95. Polish.Prusi¨½ski A, Durko A, Niczyporuk-Turek A.Katedra i Klinika Neurologii Akademii Medycznej w Lodzi.
Feverfew has been used in traditional medicine in the treatment of migraine for a long time. In 1985 E.S. Johnson et al. and later J.J. Murphy et al., 1988 and B.K. Vogler et al., 1994 published positive results of prophylactic use of this herb in migraine. Since 1994 through 1996 we studied in our Centre of Migraine Therapy the efficacy of feverfew in migraine treatment. We had 24 patients (women 19-61 years old) in our group. The drug was administered once daily (5 ml of the sap) for 30-60 days. We observed significant reduction of Migraine Index in 8 patients, less significant in additional 5. Our results confirm that feverfew may be beneficial in migraine prophylaxis as an additive drug. Further controlled studies need to be done, especially to establish the optimal dose of the drug.
Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats.:J Ethnopharmacol. 1999 Dec 15;68(1-3):251-9.Jain NK, Kulkarni SK.Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.
Rapid extraction and high-performance liquid chromatographic determination of parthenolide in feverfew (Tanacetum parthenium).:J Agric Food Chem. 1999 Mar;47(3):1018-22.Zhou JZ, Kou X, Stevenson D.Department of Research and Development, Nature's Sunshine Products, Inc., 1655 North Main Street, Spanish Fork, Utah 84660, USA. JosephZ@Natr.com
A rapid and sensitive method for quantifying parthenolide in feverfew herb (Tanacetum parthenium) was developed that is significantly faster than those reported in the literature. The extraction system consisted of acetonitrile/water (90:10, v/v) in a bottle with stirring for 30 min. Both Soxhlet and bottle-stirring extractions were studied. Samples were analyzed using high-performance liquid chromatography with a Cosmosil C18-AR column (150 x 4.6 mm, 5 microm, 120 A). The mobile phase consisted of acetonitrile/water (55:45, v/v) with a flow rate of 1.5 mL/min and UV detection at 210 nm. Analysis time was 6 min, with a detection limit of 0.10 ng on column. The calibration curve was linear over a range of 0.160-850 microg/mL parthenolide with R(2) = 0.9999. Replicate tests indicated good reproducibility of the method with an RSD% = 0.88 (n = 10). Spike recovery of parthenolide was found to be 99.3% with an RSD% = 1.6 (n = 6).
The flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory properties:Phytochemistry. 1999 Jun;51(3):417-23. Erratum in: Phytochemistry 1999 Nov;52(6):1181-2.Williams CA, Harborne JB, Geiger H, Hoult JR.Department of Botany, University of Reading, UK.
The lipophilic flavonoids in leaf and flower of Tanacetum parthenium and T. vulgaris have been compared. While those of T. parthenium are methyl ethers of the flavonols 6-hydroxykaempferol and quercetagetin, the surface flavonoids of T. vulgare are methyl ethers of the flavones scutellarein and 6-hydroxyluteolin. Apigenin and two flavone glucuronides are surprisingly present in glandular trichomes on the lower epidermis of the ray florets of T. parthenium. The opportunity has been taken to revise the structures of the four 6-hydroxyflavonol methyl ethers of T. parthenium based on NMR measurements. These are now shown to be uniformly 6- rather than 7-O-methylated. Tanetin, previously thought to be a new structure, is now formulated as the known 6-hydroxykaempferol 3,6,4'-trimethyl ether. The vacuolar flavonoids of both plants are dominated by the presence of apigenin and luteolin 7-glucuronides; nine other glycosides were present, including the uncommon 6-hydroxyluteolin 7-glucoside in T. vulgare. When the major flavonol and flavone methyl ethers of the two plants were tested pharmacologically, they variously inhibited the major pathways of arachidonate metabolism in leukocytes. There were significant differences in potency, with the tansy 6-hydroxyflavones less active than the feverfew 6-hydroxyflavonols as inhibitors of cyclo-oxygenase and 5-lipoxygenase.
Low concentrations of the feverfew component parthenolide inhibit in vitro growth of tumor lines in a cytostatic fashion.:Planta Med. 1999 Mar;65(2):126-9.Ross JJ, Arnason JT, Birnboim HC.Department of Biology, University of Ottawa, Ontario, Canada.
Parthenolide, a clinically useful agent and migraine prophylaxis principle from the medicinal plant, feverfew (Tanacetum parthenium), was tested on two tumor cell lines for its ability to inhibit cell growth. At concentrations above 5.0 microM and an exposure time of 24 h, parthenolide inhibited cell growth in an irreversible fashion. However, at lower concentrations, the effect was reversible; parthenolide acted in a cytostatic fashion over multiple cell generations for mouse fibrosarcoma (MN-11) and human lymphoma (TK6) cell lines. After 24 h exposure to 2.5 microM parthenolide, approx. 85% of cells were able to continue cell cycling on removal of the chemical, as demonstrated by labeling of S-phase cells with BrdU. In a clonogenic assay, colony formation was also unchanged by exposure to this concentration of parthenolide. No indication of cell synchronization could be found, as evidenced by the lack of appearance of a peak of mitotic figures when cells were examined at 1 h intervals for 10 h after drug removal. The mechanism of the reversible growth inhibition is uncertain.
A review of 12 commonly used medicinal herbs.:Arch Fam Med. 1998 Nov-Dec;7(6):523-36. Review.O'Hara M, Kiefer D, Farrell K, Kemper K.Robert Wood Johnson Clinical Scholars Program, University of Washington Health Sciences Center, Seattle 98195, USA. maryanno@u.washington.edu
A large and increasing number of patients use medicinal herbs or seek the advice of their physician regarding their use. More than one third of Americans use herbs for health purposes, yet patients (and physicians) often lack accurate information about the safety and efficacy of herbal remedies. Burgeoning interest in medicinal herbs has increased scientific scrutiny of their therapeutic potential and safety, thereby providing physicians with data to help patients make wise decisions about their use. This article provides a review of the data on 12 of the most commonly used herbs in the United States. In addition, we provide practical information and guidelines for the judicious use of medicinal herbs.
The content of parthenolide and its yield per plant during the growth of Tanacetum parthenium.:Planta Med. 1997 Aug;63(4):356-9.Hendricks H, Anderson-Wildeboer Y, Engels G, Bos R, Woerdenbag HJ.Department of Pharmaceutical Biology, University Centre for Pharmacy, Groningen Institute for Drug Studies (GIDS), Antonius Deusinglaan 1, NL-9713 AV Groningen, The Netherlands.
During the growth of Tanaceum parthenium (L.) Schultz-Bip. Feverfew, Asteraceae) the percentage of parthenolide was the highest at an early stage (just before the formation of stems). The yield of parthenolide per individual plant gradually increased from about 10 mg at the beginning of the study to about 20 mg when the plant was in full bloom. Parthenolide was present in the leaves and flowerheads, but not in the stems. Drying at ambient temperature and lyophilisation had no negative influence on the yield of parthenolide per individual plant on comparing the results with those of fresh plant material. Based on the results of this study and on data from the literature we propose to distinguish two qualities of feverfew: a: Tanaceti parthenii folium (feverfew leaf), harvested at an early stage before the formation of the stems and b: Tanaceti parthenii herba (feverfew herb), harvested at full bloom, with a minimum parthenolide content of 0.50% and 0.20%, respectively, calculated on a dry weight basis. Both drugs can be easily distinguished by means of microscopic examination.
Pharmacological activity of feverfew (Tanacetum parthenium (L.) Schultz-Bip.): assessment by inhibition of human polymorphonuclear leukocyte chemiluminescence in-vitro.:J Pharm Pharmacol. 1997 May;49(5):558-61.Brown AM, Edwards CM, Davey MR, Power JB, Lowe KC.Department of Life Science, University of Nottingham, University Park, UK.
The bioactivity of feverfew (Tanacetum parthenium) leaf extracts has been analysed, by use of a human polymorphonuclear leukocyte (PMNL) bioassay, to assess the relative contributions of solvent extraction and parthenolide content to the biological potency of the extract. Extracts prepared in acetone-ethanol (system 1) contained significantly more parthenolide (mean +/- s.d. 1.3 +/- 0.2% dry leaf weight) than extracts in chloroform-PBS (phosphate-buffered saline; system 2; 0.1 +/- 0.04% dry leaf weight) or PBS alone (system 3; 0.5 +/- 0.1% dry leaf weight). Extract bioactivity, measured as inhibition of phorbol 12-myristate 13-acetate-induced, 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)-enhanced PMNL, chemiluminescence, followed a similar trend. Extracts inhibited phorbol 12-myristate 13-acetate-induced oxidative burst by amounts which, if solely attributable to parthenolide, indicated parthenolide concentrations for the respective solvent systems of 2.2 +/- 0.6%, 0.2 +/- 0.1% and 0.9 +/- 0.1% dry leaf weight. The mean ratio of parthenolide concentration to the parthenolide equivalent/PMNL-bioactivity value, for acetone-ethanol and PBS extracts were both 1:1.7. Parthenolide, although a key determinant of biological activity for T. parthenium leaf extracts based on the PMNL-bioassay, seems not to be the sole pharmacologically-active constituent. The identical and elevated bioactivity-parthenolide ratios for both organic and aqueons-phase leaf extracts suggest that a proportion of the other bioactive compounds have solubilities similar to that of parthenolide.
Parthenolide inhibits the contractile responses of rat stomach fundus to fenfluramine and dextroamphetamine but not serotonin:J Ethnopharmacol. 1996 Jan;50(1):1-12.B¨¦jar E.Research Institute of Pharmaceutical Sciences, University of Mississippi, University 38677, USA.
The isolated rat stomach fundus preparation, a sensitive bioassay to evaluate serotonin-(5-HT) like activity, was used as a model to study the effects of parthenolide (PAR), a component to Tanacetum parthenium (feverfew), on 5-HT storage, release and stimulation of the 5-HT2B receptor. Cumulative-concentration response curves to 5-HT and the indirect-acting serotonergics fenfluramine (F) and dextroamphetamine (DA) on fundus were obtained in the presence and absence of 1 x 10(-6) to 1 x 10(-5) PAR. 5-HT release elicited by F and DA was indirectly assessed by comparing the contraction elicited by these compounds on tissues from reserpine-treated, L-p-chlorophenylalanine (l-PCPA)-treated and untreated rats. The observed order of agonist potencies on intact fundus was: 5-HT > DA > F and the order of intrinsic activity was: 5-HT > DA > F. PAR did not show agonist effects nor antagonism toward 5-HT on rat fundus at all concentrations used. However, PAR antagonized non-competitively the effects of F and DA. Contractile responses to 5-HT were not significantly different on mucosa-denuded fundus and tissue strips from untreated, l-PCPA- and reserpine-treated rats. PAR appears to inhibit 5-HT release mediated responses by the indirect-acting 5-HT agonists on fundal tissue.
A biologically active lipophilic flavonol from Tanacetum parthenium.:Phytochemistry. 1995 Jan;38(1):267-70.Williams CA, Hoult JR, Harborne JB, Greenham J, Eagles J.Department of Botany, School of Plant Sciences, University of Reading, Whiteknights, Berkshire, U.K.
A new lipophilic flavonol, 6-hydroxykaempferol 3,7,4'-trimethyl ether, called tanetin, has been characterized in the leaf, flower and seed of feverfew, Tanacetum parthenium. It co-occurs with the known 6-hydroxykaempferol 3,7-dimethyl ether, quercetagetin 3,7-dimethyl ether and quercetagetin 3,7,3'-trimethyl ether. Pharmacological tests indicate that tanetin could contribute to the anti-inflammatory properties of feverfew by inhibiting the generation of pro-inflammatory eicosanoids, although it is unlikely to be the only biologically active compound within the plant. Water soluble flavone glycosides were detected in the leaves and identified as apigenin 7-glucuronide, luteolin 7-glucuronide, luteolin 7-glucoside and chrysoeriol 7-glucuronide.
Feverfew and vascular smooth muscle: extracts from fresh and dried plants show opposing pharmacological profiles, dependent upon sesquiterpene lactone content.:Planta Med. 1993 Feb;59(1):20-5.Barsby RW, Salan U, Knight DW, Hoult JR.Pharmacology Group, King's College London, U.K.
Preparations of fresh or dried feverfew (Chrysanthemum parthenium) are widely consumed in the U.K. as a remedy for arthritis and migraine, but the pharmacological basis for this has not been established. We have, therefore, compared the properties of extracts of fresh plants with those of dried powdered leaves available commercially from health food shops. The two extracts differed radically in their content of alpha-methylbutyrolactones and in their pharmacological profile when tested in vitro on the rabbit aortic ring and rat anococcygeus preparations. Extracts of fresh leaves caused does- and time-dependent inhibition of the contractile responses of aortic rings to all receptor-acting agonists so far tested; the effects were irreversible and may represent a toxic modification of post-receptor contractile function in the smooth muscle. The presence of potentially -SH reactive parthenolide and other sesquiterpene alphamethylenebutyrolactones in these extracts, and the close parallelism of the actions of pure parthenolide, suggest that the inhibitory effects are due to these compounds. In contrast , chloroform extracts of dried powdered leaves were not inhibitory but themselves elicited potent and sustained contractions of aortic smooth muscle that were not antagonised by ketanserin (5-HT2 receptor antagonist). These extracts did not contain parthenolide or butyrolactones according to a chemical-HPLC assay, We conclude that there are marked differences in the pharmacological potency and profiles between preparations from fresh and dried feverfew and that this may relate to their lactone content. As the effects of the lactones are potentially toxic, it will be necessary to compare the clinical profiles and side effects of preparations obtained from the two sources.
Feverfew extracts and parthenolide irreversibly inhibit vascular responses of the rabbit aorta.:J Pharm Pharmacol. 1992 Sep;44(9):737-40.Barsby RW, Salan U, Knight DW, Hoult JR.Pharmacology Group, King's College London, UK.
Samples prepared from chloroform extracts of fresh leaves of feverfew (Tanacetum parthenium) strongly inhibited responses of rabbit aortic rings to phenylephrine, 5-hydroxytryptamine, thromboxane mimetic U46619 (9,11-dideoxy-11 alpha,9 alpha-epoxy-methano-PGF2 alpha), and angiotensin II, but the inhibition to contractions induced by potassium depolarization was much less. The inhibition was concentration- and time-dependent, non-competitive, and irreversible, and also occurred in endothelium-denuded preparations. The feverfew extracts also caused a progressive loss of tone of pre-contracted aortic rings and appeared to impair the ability of acetylcholine to induce endothelium-dependent relaxations of the tissue. These effects were mimicked by a purified preparation of an alpha-methylenebutyrolactone, parthenolide, obtained from the extract. Our results demonstrate a nonspecific and potentially toxic response to feverfew on the vasculature.
Attempts of chemical standardizing of Chrysanthemum parthenium as a prospective antimigraine drug.:Pol J Pharmacol Pharm. 1991 May-Jun;43(3):213-7.Gromek D, Kisiel W, Stojakowska A, Kohlm¨¹nzer S.Department of Phytochemistry, Polish Academy of Sciences, Krak¨®w.
A quantitative analysis of biologically active sesquiterpene lactones in ethanol and aqueous extracts of Chrysanthemum parthenium and its form flosculosum was carried out. The sesquiterpene lactone contents in the extracts were comparable, although the contents of ethanol extracts (ca. 0.5%) were higher than of aqueous ones (ca. 0.3%). Parthenolide was found to be the main constituent of the lactones. The applied IR and TLC/FID methods for quantitative determination of the total sesquiterpene lactones and parthenolide, respectively, may be used for chemical standardizing of the raw material and its preparations.
A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro.:J Pharm Pharmacol. 1990 Aug;42(8):553-7.Groenewegen WA, Heptinstall S.Department of Medicine, University Hospital, Nottingham, UK.
Extracts of the herb feverfew inhibit human blood platelet aggregation and secretion induced by a number of agents in-vitro and this may relate to the beneficial effects of feverfew in migraine. We previously identified several compounds with antisecretory activity in human blood platelets using adrenaline as the stimulant. In the present study, we have compared the inhibitory activity of one of these compounds, parthenolide, with that of crude feverfew extract. The effects of both on [14C]5-HT secretion from platelets and on platelet aggregation induced by a number of different stimulants were determined. The activating agents studied included the phorbol ester PMA, ADP, arachidonic acid, collagen, the thromboxane mimetic U46619, the calcium ionophore A23187, the diacylglycerol analogue OAG and adrenaline. The results show that there are marked similarities between the effects of feverfew extract and of parthenolide on both [14C]5-HT secretion and platelet aggregation, which is consistent with the effects of feverfew extract on platelets being brought about by parthenolide or similar compounds in the extract. Only in one case, when A23187 was used as the stimulatory agent, was there any discrepancy, which may have been due to materials in the extract other than parthenolide. Both feverfew extract and parthenolide were more effective as inhibitors of the [14C]5-HT secretion and aggregation induced by some agents and not others, and were most effective as inhibitors of the [14C]5-HT secretion (but not the aggregation) induced by PMA. This suggests that the effects of feverfew/parthenolide on the protein kinase C pathway warrants further study.
Feverfew in rheumatoid arthritis: a double blind, placebo controlled study.:Ann Rheum Dis. 1989 Jul;48(7):547-9.Pattrick M, Heptinstall S, Doherty M.Rheumatology Unit, City Hospital, Nottingham.
Feverfew, reputed by folklore to be effective in arthritis, has in vitro properties that could be beneficial in the control of inflammatory disease. Forty one female patients with symptomatic rheumatoid arthritis received either dried chopped feverfew (70-86 mg) or placebo capsules once daily for six weeks. Allocation was random and not known by patient or observer. Variables assessed included stiffness, pain (visual analogue scale), grip strength, articular index, full blood count, erythrocyte sedimentation rate, urea, creatinine, C reactive protein, complement breakdown products (C3dg), rheumatoid factor titre, immunoglobulins (IgG, IgA, IgM), functional capacity, and patient and observer global opinions. One patient (placebo) withdrew after three days and was not included in the analysis. Treatment and placebo groups (20 patients each) were well matched at entry. No important differences between the clinical or laboratory variables of the groups were observed during the six week period. This study therefore shows no apparent benefit from oral feverfew in rheumatoid arthritis.
Prostaglandin synthetase inhibitors in feverfew.:J Pharm Pharmacol. 1988 Oct;40(10):743-5.Pugh WJ, Sambo K.Welsh School of Pharmacy, UWIST, Cardiff, UK.
The IC50 values for the in-vitro inhibition of the prostaglandin synthetase (bovine seminal vesicle mitochondrial fraction) mediated PGE2 production from arachidonic acid by parthenolide, michefuscalide and chrysanthenyl acetate were 11.0 +/- 0.44, 12.1 +/- 0.51 and 14.2 +/- 0.58 microM (mean +/- 95% confidence limits), respectively.
Randomised double-blind placebo-controlled trial of feverfew in migraine prevention:Lancet. 1988 Jul 23;2(8604):189-92.Murphy JJ, Heptinstall S, Mitchell JR.Department of Medicine, University Hospital, Nottingham.
The use of feverfew (Tanacetum parthenium) for migraine prophylaxis was assessed in a randomised, double-blind, placebo-controlled crossover study. After a one-month single-blind placebo run-in, 72 volunteers were randomly allocated to receive either one capsule of dried feverfew leaves a day or matching placebo for four months and then transferred to the other treatment limb for a further four months. Frequency and severity of attacks were determined from diary cards which were issued every two months; efficacy of each treatment was also assessed by visual analogue scores. 60 patients completed the study and full information was available in 59. Treatment with feverfew was associated with a reduction in the mean number and severity of attacks in each two-month period, and in the degree of vomiting; duration of individual attacks was unaltered. Visual analogue scores also indicated a significant improvement with feverfew. There were no serious side-effects.
Effects of an extract of feverfew on endothelial cell integrity and on cAMP in rabbit perfused aorta.:J Pharm Pharmacol. 1988 Jul;40(7):501-2.Voyno-Yasenetskaya TA, Loesche W, Groenewegen WA, Heptinstall S, Repin VS, Till U.Institute of Experimental Cardiology, USSR Cardiology Research Centre, Moscow.
Extracts of feverfew inhibit platelet aggregation and secretion of granular contents from platelets and other cells. They also modify the interaction of platelets with collagen substrates: feverfew extracts inhibit both platelet spreading and formation of thrombus-like platelet aggregates on the collagen surface. We have now investigated the effect of an extract of feverfew on the vessel wall using rabbit aortas that were perfused with a physiological salt solution in-situ. Addition of feverfew extract to the perfusion medium protected the endothelial cell monolayer from perfusion-induced injury and led to a reversible increase in the cAMP content of aorta segments. The results indicate that feverfew may have a vasoprotective effect in addition to its effects on platelets.
New Chlorine-Containing Sesquiterpene Lactones from Chrysanthemum parthenium.:Planta Med. 1988 Apr;54(2):171-2.Wagner H, Fessler B, Lotter H, Wray V.Institute for Pharmaceutical Biology, University of Munich, Karlstr.29, D-8000 M¨¹nchen, Federal Republic of Germany.
From the leaves of CHRYSANTHEMUM PARTHENIUM (L.) Bernh. (feverfew) two new chlorine-containing sesquiterpene lactones were isolated and structurally elucidated, mainly by NMR spectroscopy and X-ray analysis.
Effects of an extract of feverfew (Tanacetum parthenium) on arachidonic acid metabolism in human blood platelets.:Biomed Biochim Acta. 1988;47(10-11):S241-3.Loesche W, Groenewegen WA, Krause S, Spangenberg P, Heptinstall S.Institute of Pathological Biochemistry, Medical Academy of Erfurt, GDR.
It has been suggested that feverfew extracts (FE) inhibit platelet behaviour via effects on platelet sulphydryl (SH) groups. In the present study we found evidence that FE inhibits uptake as well as liberation of arachidonic acid (AA) into/from platelet membrane phospholipids (PL).
The activity of compounds extracted from feverfew on histamine release from rat mast cells.:J Pharm Pharmacol. 1987 Jun;39(6):466-70.Hayes NA, Foreman JC.
An extract of the plant feverfew (Tanacetum parthenium) produces a dose-dependent inhibition of histamine release from rat peritoneal mast cells stimulated with anti-IgE or the calcium ionophore A23187. Greater inhibition of anti-IgE-induced histamine release was achieved with feverfew compared with the inhibition of A23187-induced release. Inhibition of anti-IgE-induced histamine release by feverfew extract was observed when the drug was added simultaneously with anti-IgE and the inhibitory activity increased only slightly when the drug was preincubated with the cells for 5 min before anti-IgE stimulation. In this respect feverfew differs from cromoglycate and quercetin. Feverfew extract inhibited anti-IgE-induced histamine release to the same extent in the absence and presence of extracellular glucose. It is concluded that feverfew extract contains a novel type of mast cell inhibitor.
The effect of an aqueous extract of Tanacetum parthenium L. on arachidonic acid metabolism by rat peritoneal leucocytes.:J Pharm Pharmacol. 1986 Jan;38(1):71-2.Capasso F.
The effect of feverfew (Tanacetum parthenium L., Schultz Bip.) as a whole plant on an aqueous extract equivalent to 20 mg dried plant per ml, has been examined on both cyclo-oxygenase and lipoxygenase activity in rat leucocytes in-vitro. At 10-25 micrograms ml-1 feverfew had no effect on the formation of arachidonate metabolites while at highest concentrations (50-200 micrograms ml-1) it inhibited both cyclo-oxygenase and lipoxygenase metabolic products.
Scientific References:
1.Research Update:FeverFew or Tanacetum parthenium.
Claims & Warning:
Claims: Information this web site presented is meant for Nutritional Benefit and as an educational starting point only, for use in maintenance and promotion good health in cooperation with a common knowledge base reference...Furthermore,it based solely on the traditional and historic use or legend of a given herb from the garden of Adonis. Although every effort has been made to ensure its accurate, please note that some info may be outdated by more recent scientific developments......
Pharmakon Warning: The order of knowledge is not the transparent order of forms and ideas,as one might be tempted retrospectively to interpret it; it is the antidote....(Dissemination,Plato's Pharmacy,II.The Ingredients:Phantasms,Festivals,and Paints;138cf. Jacques Derrida.).
And as it happens,the technique of imitation,along with the production of the simulacrum,has always been in Plato's eyes manifestly magical,thaumaturgical:......and the same things appear bent and straight to those who view them in water and out,or concave and convex,owing to similar errors of vision about colors, and there is obviously every confusion of this sort in our souls.And so scene painting (skiagraphia) in its exploitation of this weakness of four nature falls nothing short of witchcraft (thaumatopoia), and so do jugglery and many other such contrivances.(Republic X,602c-d;cf.also 607c).
seminal trace...Feverfew Extract.Tanacetum parthenium.10:1.Reduces Migraine Frequency.Parthenolide.5-Hydroxytryptamine-inhibiting.Formula: C15H20O3.Chemical Family:Alkaloids.CAS No: 20554-84-1...
Phytochemical info of FeverFew or Tanacetum parthenium
Identification of antioxidant phenolic compounds in feverfew (Tanacetum parthenium) by HPLC-ESI-MS/MS and NMR:Phytochem Anal. 2007 Sep;18(5):401-10.Wu C, Chen F, Wang X, Wu Y, Dong M, He G, Galyean RD, He L, Huang G.Department of Food Science and Human Nutrition, Clemson University, Clemson, SC 29634, USA. changqi@clemson.edu
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Claims & Warning:
