Feverfew

Botanical Description & Habitat

Chrysanthemum parthenium

Family
Asteraceae

Common names

Featherfew	Featherfoil
Febrifuge plant	Pyrethrum
Wild quinine

Habitat
Cultivated and found wild in North America and Europe. It is a perennial plant flourishing in waste places, along roadsides, and wood borders.

Description
Has a thick, dark brown root with furrowed bark. The stem is smooth, branched, and erect, growing to two feet in height. It produces alternate, petiolate, bipinnate leaves with ovate leaflets. Large yellow pedunculate flowers grow at the end of the stems and branches, appearing in June and July.

Medicinal parts
Flower heads - collected just at maturity

Historical Properties & Uses

Feverfew has a long folk history in the treatment of fever, arthritis, and migraine. Its name is actually a corruption of the term febrifuge, meaning "that which lessens fever." Whole leaves and leaf extracts are the most commonly used medicinal preparations of the herb.

Feverfew is used as an anti-inflammatory agent to treat fevers, migraine headaches, and rheumatoid arthritis. Extensive clinical tests verify its effectiveness in the prevention and relief of migraine symptoms. Many people who have had poor luck with other treatments respond to feverfew. However, like other treatments for migraine, it may not be effective for every sufferer. The herb's action is similar to that of aspirin. Both inhibit the inflammation process, but there are significant differences between them as well.

Feverfew has been used for regulation of menstruation, threatened miscarriage, difficult labor, and stomach ache. However, these uses have not been investigated. Its effect on toothache and insect bites may be related to the herb's aspirin and antihistaminic properties.

Some people are sensitive to feverfew, and may develop contact dermatitis and/or ulcerations and sores of the mouth with prolonged use. These aphthous ulcerations resemble those often seen in people using aspirin and other non-steroidal anti-inflammatory drugs for the treatment of arthritis.

Method of Action

Feverfew reduces frequency and severity of migraine headaches
In one survey of 270 migraine sufferers who had eaten feverfew leaves every day for prolonged periods, 72% reported decreased frequency of attacks or less painful attacks or both, while 24% reported no change, and 2% reported getting worse. It was determined 88% of the patients suffered from true migraine. The vast majority of these sufferers reported other medications and treatments were ineffective, and that's why they had started using feverfew after reading about it in the popular press.

In another study, 17 patients who ate fresh leaves of feverfew daily to prevent migraine participated in a double blind placebo controlled trial of the herb: eight patients received capsules containing freeze dried feverfew powder (instead of the fresh leaf the patients had been using), and nine received placebo. Those who received placebo reported a significant increase in the frequency and intensity of headache, nausea, and vomiting; these effects began to occur soon after treatment began. The feverfew group experienced no change in the frequency or intensity of attacks. Although the design of this experiment was a little weak in many respects, it nevertheless provides good evidence for an anti-migraine effect in feverfew.

The seemingly highly significant results of this study must be viewed in the restricted context of the controlled withdrawal experimental design; it must be remembered, for example, the subject pool automatically excluded anybody who could not tolerate feverfew or who found the plant ineffective in treating migraine. It is also likely all patients taking placebo quickly realized it, a fact that may have intensified their perceptions and reactions, and at least violated the preconditions for a double-blind study. Also, one could have hoped for a more robust statistical treatment of the results than a Wilcoxon rank sum test. Statistical and design considerations aside, however, there is little doubt there was some real difference between the groups that could be attributed to the treatment.

Cellular mechanisms underlying feverfew action
Two hypotheses have been proposed for the mechanism of action of feverfew; both are supported by the available research. Both involve the inhibition of prostaglandin biosynthesis, but differ in their emphasis on the particular pathway involved.

The first, and most popular, theory is based on findings feverfew extracts apparently inhibit thromboxane synthesis through inactivation of cellular phospholipases, which in turn prevents release of thromboxane precursors (arachidonic acid) in response to appropriate physiological stimuli. Feverfew extracts were found to inhibit ADP, thrombin, or collagen-induced aggregation of human platelets (which involve synthesis of the proaggregatory prostaglandin thromboxane A2), but importantly, did not affect aggregation induced by arachidonic acid. Inhibition must, therefore, be "upstream" from arachidonic acid. Synthesis of thromboxane B2 from exogenous 14C-arachidonic acid was also not inhibited. Washed platelets prelabelled with 14C-AA responded normally to thrombin by releasing 14C-TXB2. This was completely blocked by feverfew extract. A purified platelet phospholipase A2 was inhibited.

In summary, the antifebrile and anti-platelet activities of feverfew was apparently due to a phospholipase inhibitor which prevented the release of arachidonic acid normally induced by appropriate exposure to aggregatory agents. Since arachidonic acid is the precursor both of prostaglandins and leukotrienes, including the slow reacting substance of anaphylaxis, these observations may explain the observed effects of feverfew in migraine and arthritis.

The second theory was inspired by findings feverfew extracts did not always inhibit thromboxane synthesis in platelets. The outcome was found to depend on the aggregating agents used. Feverfew had little effect on the thromboxane synthesis induced by sodium arachidonic acid, ADP, or thrombin, but that induced by adrenaline was reduced to levels below the sensitivity of the assay. The extract as inhibited adrenaline-induced platelet aggregation. Thus a new mechanism was sought. It was found in the apparent inhibition of protein kinase C pathway.

Feverfew extracts inhibited secretory activity in blood platelets and polymorphonuclear leukocytes (PMNs). They also inhibited the release of 14C-serotonin from platelets induced by various aggregating agents. They also inhibited release of vitamin B-12 binding protein from PMNs induced by several secretagogues. The extracts did not inhibit the secretion induced in platelets or PMNs by the calcium inophore A23187.

This pattern of effects is different from that obtained with other platelet aggregation inhibitors, and the effect on PMNs is more pronounced than has been obtained with very high concentrations of non-steroidal anti-inflammatory agents, such as aspirin.

Enzymes from intracellular granules in PMNs are found in synovial fluid in rheumatoid arthritis, and there is evidence serotonin, a platelet granule component, contributes to migraine. Inhibition of PMN degranulation could reduce PMN-induced damage to the rheumatoid synovium and reduction of platelet serotonin release could minimize the changes in the vascular tone associated with migraine.

Cytotoxic and anti-microbial properties of parthenolide
Parthenolide has been shown to possess cytotoxic properties when tested against three different human cell lines, as well as against Eagle's 9KB carcinoma of the nasopharynx cell culture system; activity was registered at a level of 0.45 micrograms/milliliter.

Parthenolide has been found to inhibit the growth of several gram positve bacteria in nutrient broth, including Bacillus meaterium, B. cereus, B. subtilis, Micrococcus lysodeikticus, Mycobacterium sp., Staphylococcus aureus and S. albus. It is ineffective against Streptococcus sp. and gram negative bacteria. It inhibits yeasts and to a much lesser extent filamentous fungi. Most sensitive to parthenolide were bacillus species without endospores.

Spasmolytic property of feverfew lactones
Parthenolide and several similar sesquiterpene lactones isolated from feverfew have been shown to have spasmolytic properties. That is, they render smooth muscle non-selectively less responsive to endogenous substances such as noradrenaline, acetylcholine, bradykinin, prostaglandins, histamine and serotonin in a non-competitive manner.

Drug Interactions & Precautions

Known Interactions
In cathartic doses feverfew may potentiate anticoagulant therapy by reducing absorption of vitamin K from the gut. It may also inhibit absorption of dextrose and sucrose from the intestines.

Conversely the herb, at cathartic doses, may decrease intestinal transit time of digitalis glycosides, inhibit their absorption and cardiac action. Cathartic-induced hypokalemia, however, increases toxicity and potency of absorbed digitalis and potentiates muscle relaxants. In addition to the specific interactions listed, the cathartic action of feverfew tends to hasten the passage of all oral medications through the gut, thereby inhibiting their action.

Feverfew inhibits platelet aggregation in vitro i.e. it may have an anticoagulant effect.

Feverfew Monograph. In: Burnham TH, Hagemann RC, Threlkeld DS (eds.) The Lawrence Review of Natural Products. St. Louis: Facts and Comparisons. 1994.

Comments
The psycho- and physico-stimulant properties of feverfew may be assumed to interact in presently unknown ways with other psychoactive, central and peripheral nervous system stimulants and depressants.

Safety Factors & Toxicity

Hundreds of people have used feverfew in clinical settings, and under trained observation, without incidence of significant side effects. Those people, however, can be characterized as a self-selected population which is not allergic to the plant. A certain percentage of the population is very sensitive to feverfew.

In animal experiments and in observations of human response, it has been established that parthenolide, a cytotoxic and antifungal constituent of feverfew, found on the outer surfaces of leaves and seeds, can produce severe allergic contact dermatitis. Parthenolide is a sesquiterpene lactone. Hundreds of these lactones have been identified in the plant kingdom, and many have a strong irritant potential for sensitive people.

Preparation & Administration

Three times a day

Dried leaf
25 mg

Fluid extract
1:1 in 25% alcohol, 15-20 drops

Tincture
1:5 in 45% alcohol, 30-40 drops

Note: This Herbal Preparation information is a summary of data from books and articles by various authors. It is not intended to replace the advice or attention of health care professionals.

Abstracts

References

Am Hospital Formulary Service. Am Soc of Hosp Pharm. Wash, D.C.

Awang, DVC: Herbal medicine, feverfew. Can. Pharm. J. 1989, 122:266.

Azarnoff, D. & A. Hurwitz. 1970. Drug interactions. Pharmacol Physicians, 4(2). pp. 1-7.

Barsby, R.W. et al: A chloroform extract of the herb feverfew blocks voltage-dependent potassium currents recorded from single smooth muscle cells. J. Pharm. Pharmacol. 1993, 45(7): 641 - 645.

Beckman, H. 1967. Dilemmas in drug therapy. Saunders, Philadelphia.

Berry, M.I. Feverfew faces the future. The Pharmaceutical Journal, May 19, 1984, pp. 611-614.

Blakeman, J.P. & P. Atkinson. Antimicrobial properties and possible role in host-pathogen interactions of pharthenolide, a sesquiterpen lactone isolated from glands of chyrsanthemum parthenium. Physiological Plant Pathology, 15, 183-192, 1979.

Bressler, R., M.D. Bogdonoff & G.J. Subak-Sharpe. 1981. The Physicians Drug Manual. Doubleday & Co, Inc. Garden City, NY. 1213 pp.

Burnham TH, Hagemann RC, Threlkeld DS (eds.) The Lawrence Review of Natural Products. St. Louis: Facts and Comparisons. 1994. [Feverwfew monograph]

Collier, HOJ, Butt, McDonald-Gibson & Saeed. Extract of feverfew inhibits protaglandin biosynthesis. (letter) The Lancet, October 25, 1980, pp. 922-923.

Facts and Comparisons. The Lawrence Review of Natural Products. Sep, 1994.

Felter, H.W. & Lloyd, J.U. King's Am Dispensatory, 18th Ed. 1898. Reprinted by Eclectic Medical Publications: Portland, Or, 1983

Goodman, L.S. & A. Gilman. 1975. Pharm Basis of Thera. MacMillan, NY.

Groenwegen, W, Heptinstall, S. Comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity In vitro. J Pharm Pharmacol42 (1990): 553-557.

Hanington, E., R.J. Jones, J.A.L. Amess & B. Wachowicz. Migraine: a platelet disorder. The Lancet, 1981, II, 720-723.

Hansten, P.D. 1979. Drug Interactions, 4th ed. Lea & Febiger, Phila.

Hausen, B.M. & P.E. Osmundsen. Contact allergy to parthenolide in tanacetum parthenium (l.) schulz-bip. (feverfew, asteraceae) and cross-reactions to related sesquiterpene lactone containing compositae species. Acta Derm Venereol (Stockh), 63, 308-314, 1983.

Heptinstall, White, Williamson & Mitchell. Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes. The Lancet, I, May 11, 1985, pp. 1071-1074.

Heptinstall, S., J. Bevan, S. Cockbill, S. Hanley & M. Parry. Effects of a selective inhibitor of thromboxane synthetase on human blood platelet behavior. Thromboxane Research, 20, 219-230, 1980.

Hobbs, C: Feverfew. HerbalGram, 1989, 20:26.

Howe & Fordham. Polymorophonuclear leucocytes. Origins, functiions and roles in rhematic diseases.: D.W. Carson, ed. Immunological Aspects Of Rheumatology. Lancaster, Mtp Press, 1981, pp. 149-170.

Interactions of drugs. Med Let Drugs Ther, 12(11). pp. 93-96.

Jain, M.K. & D.V. Jahagirdar. Action of phospholipase A on bilayers. Effect of inhibitors. Biochimica Et Biophysica Acta, 814, 319-326, 1985.

Johnson, E.S., N. Kadam, D. Hylands & P. Hylands. Efficacy of feverfew as prophylactic treatment of migraine. BMJ, 291, 31 Aug 1985, pp. 569-573.

Johnson, E.S. Feverfew - A Traditional Herbal Remedy For Migraine And Arthritis. London, Sheldon Press, 1984.

Kastrup, E.K., ed. 1981. Drug Facts and Comparisons, 1982 edition. Facts and Comparisions Division, J.P. Lippincott Co, Phila(St. Louis).

Lee, K.H., E. Huang, C. Piantadosi, J. Pagano & T. Geissman. Cytotoxicity of sequiterpene lactones. Cancer Research, 31, 1649-1654, 1971.

Lewis, Walter H. & Elvin-Lewis, Memory P.F. Medical Botany: Plants Affecting Man's Health, John Wiley and Sons. New York, l977.

List, P. & L. Hoerhammer. 1969-1976. Hagers Hanbuch der Pharmazeutischen Praxis, vols. 2-5. Springer-Verlag, Berlin.

Makheja, A.N. & J. Bailey. A platelet phospholipase inhibitor from the medicinal herb feverfew (tanacetum parthenium). Prostaglandins Leukotrienes And Medicine, 8, 653-660, 1982.

Makheja, A.N. & J.M. Bailey. The active principle in feverfew. The Lancet, II, November 7, 1981, p. 1054.

Martin, E.W. 1978. Drug Interactions Index, 1978/79. J.B. Lippincott Company, Philadelphia.

Mitchell, J.C., T,A. Geissman, G. Dupuis & G. Towers. Allergic contact dermatitis caused by artemisia and chrysanthemum species. Journal Of Investigative Dermatology, 56(2), 98-101, 1971.

Mowrey, Daniel B., Ph.D. Exper. Psych., Brigham Young University. Director of Nebo Institute of Herbal Sciences. Director of Behavior Change Agent Training Institute. Director of Research, Nova Corp.

Pizzorno, Joseph E. & Murray, Michael T. A Textbook of Natural Medicine. John Bastyr College Publications: Seattle, Wa, 1985

Prescott, L.F. Dec. 6, 1969. Pharmacokinetic drug interactions. Lancet, 2. pp. 1239-1243.

Schulz, K.H., B.M. Hausen, L. Wallhoefer & P. Schmidt-loeffler. Chrysanthemem-allergie. Experimentelle untersuchungen zur identifizierung der allergene. Arch. Derm. Forschung, 251, 235-244, 1975.

Vickers, H.R. Contact dermatitis. Practitioner, 164, March, 1950, pp. 226-233.

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Chrysanthemum parthenium

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