Feverfew and Vascular Smooth Muscle: Extracts from Fresh and Dried Plants Show Opposing Pharmacological Profiles, Dependent upon Sesquiterpene Lactone Content

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.

Toxic inhibition of smooth muscle contractility by plant‐derived sesquiterpenes caused by their chemically reactive α‐methylenebutyrolactone functions

“…Recent studies showed that extracts of fresh leaves contain sesquiterpene xmethylenebutyrolactones such as parthenolide which cause irreversible, time-dependent and non-specific inhibition of aortic smooth muscle contractility (Barsby et al, 1992;. In contrast, extracts of dried powdered leaves available from health food shops do not inhibit aortic contractility and do not contain m-methylenebutyrolactones (Barsby et al, 1993).…”

The Combined Effect of Acupuncture and Tanacetum parthenium on quality of life in women with headache: Randomised study

“…In particular, 5-HT 1B and 5-HT 1D receptors are considered to be the main molecular targets of sumatriptan and congeners in acute treatment, 44 45 whereas 5-HT 2A and 5-HT 2C receptors are targeted by 5-HT antagonists, such as methysergide, oxetorone, pizotifen and cyproheptadine, which are used in migraine prophylaxis. [46][47][48] The mechanism of action of TAN is not well understood, but 5-HT receptor-blocking properties have been reported, [49][50][51][52] and inhibition of binding to 5-HT 2A and 5-HT 2C receptors, and to a lesser extent 5-HT 1B receptors, 53 has been suggested to play a role. There are several limitations to our study that deserve consideration.…”

Arnica Flowers: Pharmacology, Toxicolgy, and Analysis of the Sesquiterpene Lactones—Their Main Active Substances

“…This variation in the blood pressure was accounted for as a secondary action due to the effect on the heart muscle, and on the respiratory center. More recently the sesquiterpene lactone parthenolide has been demonstrated to interfere markedly with both contractile and relaxant mechanisms in vascular smooth muscle (64,65).…”