Tanacetum parthenium

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References

Barsby RW, Salan U, Knight DW, Hoult JR. 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):20-25.
Abstract: 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.

Biggs MJ, Johnson ES, Persaud NP, Ratcliffe DM. Platelet aggregation in patients using feverfew for migraine. Lancet. 1982 Oct 2;2(8301):776. (Letter)

Bradley PR, ed. British Herbal Compendium, vol 1. Bournemouth, Dorset, UK: British Herbal Medicine Association, 1992.

Brinker F. The Toxicology of Botanical Medicines. Revised second ed. Sandy, Oregon: Eclectic Medical Publications. 1996.

Brown AM, Edwards CM, Davey MR, Power JB, Lowe KC. 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):558-561.
Abstract: 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.

Christensen LP, Jakobsen HB, Paulsen E, Hodal L, Andersen KE. Airborne Compositae dermatitis: monoterpenes and no parthenolide are released from flowering Tanacetum parthenium (feverfew) plants. Arch Dermatol Res. 1999 Jul-Aug;291(7-8):425-431.

DeSmet PAG, et al. (eds) Adverse Effects of Herbal Drugs 2 NY, Springer Verlag, 1993.

De Weerdt CJ, Bootsma HPR, Hendriks H. Herbal medicines in migraine prevention. Phytomed 1996;3:225-230.

Dreisbach RH. Handbook of Poisoning: Prevention, Diagnosis, and Treatment. Tenth ed. Grand Rapids, MI: Lange Medical Publications, 1980.

Fuller TC, McClintock E. Poisonous Plants of California. Los Angeles: University of Southern California Press, 1986.

Gromek D, Kisiel W, Stojakowska A, Kohlmunzer S. Attempts of chemical standardizing of Chrysanthemum parthenium as a prospective antimigraine drug. Pol J Pharmacol Pharm. 1991 May-Jun;43(3):213-217.

Groenewegen WA, Heptinstall S. 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):553-557.
Abstract: 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.

Hepinstall S, White A, et al. Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leukocytes. Lancet 1985; i:1071-1074.

Hoffman D. The Information Sourcebook of Herbal Medicine. The Crossing Press, Freedom, CA, 1994.

Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. Br Med J 1985 Aug 31;291(6495):569-573.
Abstract: Seventeen patients who ate fresh leaves of feverfew daily as prophylaxis against migraine participated in a double blind placebo controlled trial of the herb: eight patients received capsules containing freeze dried feverfew powder and nine placebo. Those who received placebo had a significant increase in the frequency and severity of headache, nausea, and vomiting with the emergence of untoward effects during the early months of treatment. The group given capsules of feverfew showed no change in the frequency or severity of symptoms of migraine. This provides evidence that feverfew taken prophylactically prevents attacks of migraine, and confirmatory studies are now indicated, preferably with a formulation controlled for sesquiterpene lactone content, in migraine sufferers who have never treated themselves with this herb.

Johnson ES, Kadam NP, Anderson D, Jenkinson PC, Dewdney RS, Blowers SD. Investigation of possible genetoxic effects of feverfew in migraine patients. Hum Toxicol. 1987 Nov;6(6):533-534.

Knight DW. Feverfew: chemistry and biological activity. Nat Prod Rep. 1995 Jun;12(3):271-276. (Review)

Loesche W, Mazurov AV, Voyno-Yasenetskaya TA, Groenewegen WA, Heptinstall S, Repin VS. Feverfew--an antithrombotic drug? Folia Haematol Int Mag Klin Morphol Blutforsch. 1988;115(1-2):181-184.
Abstract: The effects of an extract of the plant feverfew on the interaction of platelets with surfaces coated with human collagens of type III and IV (CIII, CIV), and on the integrity of the endothelial cell (EC) monolayer in perfused rabbit aorta were studied. It was shown that feverfew extract (FE) inhibited the deposition of [51Cr]-labelled platelets on both CIII and CIV in a dose-dependent way. Similar concentrations of FE were needed to inhibit formation of surface-bound aggregates in CIII and platelet spreading on CIV in both platelet-rich plasma and GFP. When aorta segments were perfused in situ with a physiological salt solution, the addition of FE to the solution protected the EC monolayer from spontaneous injury. The results indicate that feverfew may have antithrombotic potential in addition to its claimed benefit in fever, migraine and arthritis.

Makheja AN, Bailey JM. A platelet phospholipase inhibitor from the medicinal herb feverfew (Tanacetum parthenium). Prostagland Leukotrienes Med 1982 Jun;8(6):653-660.
Abstract: Feverfew has been used since antiquity to treat fevers and other inflammatory conditions. Feverfew extracts were found to inhibit ADP, thrombin, or collagen-induced aggregation of human platelets, but significantly, did not affect aggregation induced by 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. A purified platelet phospholipase A2 was inhibited by the material with an I50 of 0.1 antiplatelet units. The pharmacological properties of feverfew may thus be due to an inhibitor of cellular phospholipases, which prevents release of arachidonic acid in response to appropriate physiological stimuli.

Makheja AN, Bailey JM. The active principle in feverfew. Lancet. 1981 Nov 7;2(8254):1054. (Letter)

Murch SJ, Simmons CB, Saxena PK. Melatonin in feverfew and other medicinal plants. Lancet. 1997 Nov 29;350(9091):1598-1599. (Letter)

Murphy JJ, Heptinstall S, Mitchell JR. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet 1988 Jul 23;2(8604):189-192.
Abstract: 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.

Palevitch D, Earon G, Carasso R. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: A double-blind placebo-controlled study. Phytother Res 1997;11:508-511.

Pattrick M, Heptinstall S, Doherty M. Feverfew in rheumatoid arthritis: a double blind, placebo controlled study. Ann Rheum Dis. 1989 Jul;48(7):547-549.

Ross JJ, Arnason JT, Birnboim HC. Low concentrations of the feverfew component parthenolide inhibit in vitro growth of tumor lines in a cytostatic fashion. Planta Med. 1999 Mar;65(2):126-129.
Abstract: 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.

Spoerke DG Jr. Herbal Medications. Santa Barbara, CA: Woodbridge Press Publishing Company, 1980.

Vogler BK, Pittler MH, Ernst E. Feverfew as a preventive treatment for migraine: a systematic review. Cephalalgia. 1998 Dec;18(10):704-708. (Review)
Abstract: 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.

Williams CA, Harborne JB, Geiger H, Hoult JR. The flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory properties. Phytochemistry. 1999 Jun;51(3):417-423.
Abstract: 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.

Wong HC. Is feverfew a pharmacologic agent? CMAJ. 1999 Jan 12;160(1):21-22.