FEVERFEW EXTRACTS AND PARTHENOLIDE IRREVERSIBLY INHIBIT VASCULAR-RESPONSES OF THE RABBIT AORTA

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.