Feverfew

Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd.

OBJECTIVE: Although a wide range of acute and preventative medications are now available for the treatment of migraine headaches, many patients will not have a significant improvement in the frequency and severity of their headaches unless lifestyle modifications are made. Also, given the myriad side effects of traditional prescription medications, there is an increasing demand for "natural" treatment like vitamins and supplements for common ailments such as headaches. Here, we discuss the role of food triggers in the management of migraines, and review the evidence for supplements in migraine treatment. METHODS: A review of the English language literature on preclinical and clinical studies of any type on food triggers, vitamins, supplements, and migraine headaches was conducted. RESULTS: A detailed nutritional history is helpful in identifying food triggers. Although the data surrounding the role of certain foods and substances in triggering headaches is controversial, certain subsets of patients may be sensitive to phenylethylamine, tyramine, aspartame, monosodium glutamate, nitrates, nitrites, alcohol, and caffeine. The available evidence for the efficacy of certain vitamins and supplements in preventing migraines supports the use of these agents in the migraine treatment. CONCLUSIONS: The identification of food triggers, with the help of food diaries, is an inexpensive way to reduce migraine headaches. We also recommend the use of the following supplements in the preventative treatment of migraines, in decreasing order of preference: magnesium, Petasites hybridus, feverfew, coenzyme Q10, riboflavin, and alpha lipoic acid.

L-3,4-dihydroxyphenylalanine (L-DOPA) is currently the main drug used to treat Parkinson's disease (PD). However, long-term use of l-DOPA causes substantial side effects, and we hope to find a biological active ingredient that synergizes with a low-dose of l-DOPA to achieve the same therapeutic effect as that of a high-dose of l-DOPA. The natural product parthenolide (PTL) is the active ingredient in the medicinal plant feverfew (Tanacetum parthenium) and has antioxidant and anti-inflammatory properties. ACT001, a fumarate salt form of dimethylaminomicheliolide (DMAMCL), is a derivative of parthenolide and has comparable effects to those of PTL but exhibits higher stability in the plasma and is available at a lower cost. In our study, we used ACT001 in combination with l-DOPA to treat 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease in mice. Specifically, ACT001 significantly reduced motor dysfunction and dopaminergic neurodegeneration in MPTP-treated mice. Furthermore, ACT001 abolished MPTP-induced α-synuclein overexpression, astrocyte activation and interleukin-1β (IL-1β) production in the substantia nigra and striatum of the mouse brain. In addition, ACT001 increased the levels of the anti-apoptotic signalling molecule Bcl-2 and the pAkt/Akt ratio and reduced the levels of the pro-apoptotic signalling molecule Bax and the activation of Caspase3 in the substantia nigra and striatum. We found that the effects of the co-administration of ACT001 and l-DOPA (5 mg/kg) were equivalent to those of the administration of 8 mg/kg l-DOPA in MPTP-induced Parkinson's disease in mice. Then, this evidence suggests that l-DOPA + ACT001 may be used for the treatment of PD.

PURPOSE: In recent years, a number of natural medicines have been reported to have inductive or inhibitive effects on the activity of drug metabolizing enzymes, upon co-administration with prescribed medicines. However, information regarding natural medicine-drug interactions that influence drug metabolism is limited owing to the lack of efficient screening method for such interactions. Therefore, to understand whether P450 activity is affected by natural medicine in small intestines, we have established frozen recombinant P450-expressing cells infected with human CYP3A4 expressing adenovirus (Ad-CYP3A4) to evaluate the effect of natural medicines on CYP3A4 activity. METHODS: Ad-CYP3A4 cells were created by infecting HepG2 cells with Ad-CYP3A4 at 10 multiplicity of infection (MOI) and these cells were stored using cryopreservation medium (fAd-CYP3A4 cells) to obtain long-term consistent data and stable supplies of cells expressing a constant level of CYP3A4 activity. RESULTS: The CYP3A4 activity in fAd-CYP3A4 cells remained unaffected at the end of each frozen period (0, 1, 2, and 6 months). Inhibitory effect on CYP3A4 activity by typical inhibitors (ketoconazole, hyperforin) and natural medicines (Cat's Claw, Devil's Claw, Feverfew, Peppermint Oil, Red Clover, and Siberian Eleuthero) were evaluated. The inhibitors had nearly equal IC50 values in fAd-CYP3A4 cells, Ad-CYP3A4 cells and recombinant CYP3A4 microsomes. Cat's Claw, Peppermint Oil and Siberian Eleuthero inhibited CYP3A4 activity more potently than 0.1 μM ketoconazole in fAd-CYP3A4 cells. CONCLUSIONS: In the present study, we have successfully developed a highly reproducible system to evaluate CYP3A4 inhibition in small intestines by natural medicines.

Comment in Semin Thromb Hemost. 2016 Apr;42(3):321-2. doi: 10.1055/s-0036-1580086. Semin Thromb Hemost. 2016 Apr;42(3):323-4. doi: 10.1055/s-0036-1580087. Cardiovascular disease (CVD) is the leading cause of death worldwide. Platelet activation and aggregation play a central role in hemostasis and thrombosis. Herbal medicines have been traditionally used in the management of CVD and can play a role in modifying CVD progression, particularly in platelet function, and have the potential of altering platelet function tests, as well as some coagulation parameters. Herbal medicines, such as feverfew, garlic, ginger, ginseng, motherwort, St John's wort, and willow bark, were found to reduce platelet aggregation. In vitro studies show promise in the reduction of platelet aggregation for Andrographis, feverfew, garlic, ginger, Ginkgo, ginseng, hawthorn, horse chestnut, and turmeric. In addition, cranberry, danshen, dong quai, Ginkgo, ginseng, green tea, and St John's wort were found to have potential interactions with warfarin. Furthermore, St John's wort interacted with clopidogrel and danshen with aspirin. Therefore, repeat testing of platelet function and coagulation studies, particularly for patients on warfarin therapy, may be required after exclusion of herbal medicines that could have possibly affected initial test results. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

157. J Prim Health Care. 2010 Dec 1;2(4):337. Feverfew. Bachelor's buttons, Featherfew (Tanacetum parthenium L. aka Chrysanthemum parthenium L. aka Pyrethrum parthenium L.). Goodyear-Smith F(1). Author information: (1)Department of General Practice and Primary Health Care, School of Population Health, The University of Auckland, Auckland, New Zealand. [email protected] PMID: 21125077 [Indexed for MEDLINE]

Metastatic melanoma is a highly life-threatening disease. The lack of response to radiotherapy and chemotherapy highlights the critical need for novel treatments. Parthenolide, an active component of feverfew (Tanacetum parthenium), inhibits proliferation and kills various cancer cells mainly by inducing apoptosis. The aim of the study was to examine anticancer effects of parthenolide in melanoma cells in vitro. The cytotoxicity of parthenolide was tested in melanoma cell lines and melanocytes, as well as melanoma cells directly derived from a surgical excision. Adherent cell proliferation was measured by tetrazolium derivative reduction assay. Loss of the plasma membrane integrity, hypodiploid events, reactive oxygen species generation, mitochondrial membrane potential dissipation, and caspase-3 activity were assessed by flow cytometric analysis. Microscopy was used to observe morphological changes and cell detachment. Parthenolide reduced the number of viable adherent cells in melanoma cultures. Half maximal inhibitory concentration values around 4 mumol/l were determined. Cell death accompanied by mitochondrial membrane depolarization and caspase-3 activation was observed as the result of parthenolide application. Interestingly, the melanoma cells from vertical growth phase and melanocytes were less susceptible to parthenolide-induced cell death than metastatic cells when drug concentration was at least 6 mumol/l. Reactive oxygen species level was not significantly increased in melanoma cells. However, preincubation of parthenolide with the thiol nucleophile N-acetyl-cysteine protected melanoma cells from parthenolide-induced cell death suggesting the reaction with intracellular thiols as the mechanism responsible for parthenolide activity. In conclusion, the observed anticancer activity makes parthenolide an attractive drug candidate for further testing in melanoma therapy.

Complementary and alternative medicine (CAM) has become increasingly popular in the United States during the last 10-15 years. The use of oral and topical supplements falls within this framework. Most oral and topical supplements are based on or include several botanical ingredients, many of which have long histories of traditional or folk medicine usage. Several of the available products derived from botanical sources are touted for their dermatologic benefits. The focus in this discussion will be on a select group of botanical compounds that have been used for dermatologic purposes or show promise for such applications, including: rosemary, polypodium leucotomos, propolis, oatmeal, olive oil, grape seed extract, lavender, mushrooms, and coffeeberry. Other more commonly used products of botanical origin, such as arnica, bromelain, caffeine, chamomile, ferulic acid, feverfew, green tea, licorice, pomegranate, and resveratrol, are also briefly considered.

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.

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.

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.

Unsafe and potentially safe herbal therapies are discussed. The use of herbal therapies is on the rise in the United States, but most pharmacists are not adequately prepared educationally to meet patients' requests for information on herbal products. Pharmacists must also cope with an environment in which there is relatively little regulation of herbal therapies by FDA. Many herbs have been identified as unsafe, including borage, calamus, coltsfoot, comfrey, life root, sassafras, chaparral, germander, licorice, and ma huang. Potentially safe herbs include feverfew, garlic, ginkgo, Asian ginseng, saw palmetto, St. John's wort, and valerian. Clinical trials have been used to evaluate feverfew for migraine prevention and rheumatoid arthritis; garlic for hypertension, hyperlipidemia, and infections; ginkgo for circulatory disturbances and dementia; ginseng for fatigue and cancer prevention; and saw palmetto for benign prostatic hyperplasia. Also studied in formal trials have been St. John's wort for depression and valerian for insomnia. The clinical trial results are suggestive of efficacy of some herbal therapies for some conditions. German Commission E, a regulatory body that evaluates the safety and efficacy of herbs on the basis of clinical trials, cases, and other scientific literature, has established indications and dosage recommendations for many herbal therapies. Pharmacists have a responsibility to educate themselves about herbal therapies in order to help patients discern the facts from the fiction, avoid harm, and gain what benefits may be available.

Herbal treatments are often used as a treatment for migraine. Therefore, an evaluation of their safety and efficacy is important. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and Cochrane Collaboration's tool for assessing the risk of bias, a systematic literature review of randomised, controlled human trials assessing the effects of herbal treatments delivered as a single ingredient for the acute or prophylactic treatment of migraine were conducted. Studies were identified through electronic database searches on Medline (Pubmed), Cochrane Library, Scopus, and CINAHL. Nineteen studies were identified examining the effects on migraine of feverfew, butterbur, curcumin, menthol/peppermint oil, coriander, citron, Damask rose, chamomile, and lavender. Overall, findings on the efficacy of feverfew were mixed and there was positive, albeit limited evidence for butterbur. There were positive, preliminary findings on curcumin, citron, and coriander as a prophylactic treatment for migraine, and the use of menthol and chamomile as an acute treatment. However, the risk of bias was high for many studies. The results of this systematic review suggest that several herbal medicines, via their multifactorial physiological influences, present as potential options to enhance the treatment of migraine. However, further high-quality research is essential to examine their efficacy and safety as a treatment for migraine. © 2020 John Wiley & Sons, Ltd.

Feverfew has been studied for the treatment of migrane in several studies and the pharmacologic mechanisms are preliminarily understood. We performed a systematic review of randomized controlled trials and present the clinical findings and potential implications. The modality of data collection and reporting in the individual studies does not support a pooling of results, but does suggest benefit of feverfew in migraine prophylaxis for at least subsets of the population with the disorder. Pharmacologically, there is some potential for concern with long-term dosing given its cyclooxygenase-2 inhibiting effects and longer-term studies will be needed to ameliorate these concerns in coronary disease patients.

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.

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.

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.

BACKGROUND: Feverfew is a popular herbal remedy advocated for the prevention of migraine. AIM: The aim of this systematic review was to look at the evidence for or against the clinical effectiveness of feverfew in migraine prevention. DATA SOURCES: Literature searches were performed using the following databases: Medline, Embase, Biosis, CISCOM, and the Cochrane Library (all from their inception to April 1998). STUDY SELECTION: Only randomized, placebo-controlled, double-blind trials were included. DATA EXTRACTION: All articles were read by two independent reviewers. Data were extracted in a predefined, standardized fashion. The methodological quality of all trials was evaluated using the Jadad score. MAIN RESULTS: Five trials met the inclusion/exclusion criteria. The majority favor feverfew over placebo. Yet important caveats exist. CONCLUSION: The clinical effectiveness of feverfew in the prevention of migraine has not been established beyond reasonable doubt.