Feverfew prostaglandins inhibition

In mast cells, histamine release induced by IgE or A23187 was also inhibited by feverfew extract [48] which also reduced spasmolytic activity of smooth muscle induced by acetylcholine, 5HT, histamine, prostaglandin E2 and bradykinin [20]. 

There are only a few reports on the efficacy of feverfew in an in vivo situation. Inhibition of collagen-induced bronchoconstriction in an in vivo guinea-pig model was demonstrated [56] and it was concluded that this was consistent with in vivo phospholipase A2 inhibition. In a rat model of experimentally induced nephrocalcinosis, parthenolide was shown to protect the rats against this condition. Inhibition of prostaglandin biosynthesis may have been the mechanism of action of parthenolide in this case, as prostaglandins are thought to be involved in nephrocalcinosis [57]. 

Parthenolide inhibits serotonin release, an action that is thought to be a likely source of its effectiveness in migraine. Extracts have also been shown to reduce the production of prostaglandins (another possible mechanism) and leukotrienes. Interestingly, melatonin has been identified in feverfew, a possibly significant observation, since chronic migraines have been associated with low melatonin levels. 

Parthenolide, a constituent of feverfew, inhibits the release of certain chemicals, including the hormone serotonin, which is produced during a migraine attack, and certain inflammatory mediators, including the hormone prostaglandin, which regulates inflammation. Feverfew is used for prevention of migraines and headaches (see Chapter 30). 

Feverfew is widely consumed in England as a remedy for arthritis and migraine. Feverfew contains parthenolide, which is a member of sesquiterpene. Parthenolide inhibits the activity of prostaglandin synthetase. It also inhibits platelet aggregation and alter serotonin release (Figure 25.2). 

Feverfew has been used as an anti-inflammatory agent to treat rheumatoid arthritis. In vitro inhibition of prostaglandin, thromboxane, and leukotriene B4 synthesis as well as cytokine (TNF- and IL-1) expression have been reported. 

Feverfew 1. Antimigraine drugs, e.g. sumatriptan t risk of episodes of tachycardia and hypertension (may be dangerous) The parthenolide constituent of feverfew has been shown to inhibit the release of serotonin and prostaglandins. Sumatriptan is an SSRI Avoid concomitant use... 

The symptoms relieved by feverfew, are also relieved by acetylsalicylate, which probably acts as an inhibitor of prostaglandin (PG) biosynthesis [227]. Therefore the aqueous extract of feverfew has been tested for ability to inhibit PG biosynthesis and it was foimd that this extract suppressed 86-88% of PG production but did not inhibit cyclooxygenation [188]. 

Feverfew s mechanism of action in the prevention of migraine headaches is not known. It is speculated that feverfew affects platelet activity or inhibits vascular smooth-muscle contraction, perhaps by inhibiting prostaglandin synthesis (4). Results of in vitro studies suggest that rather than acting as a cyclooxygenase inhibitor, feverfew inhibits phospholipase A2, thus inhibiting release of arachidonic acid from the cell membrane phospholipid bilayer (11,12). 

Organic and aqueous feverfew powdered leaf extracts were found to inhibit IL-1-induced prostaglandin E2 release from synovial cells, IL-2-induced thymidine uptake by lymphoblasts, and mitogen-induced uptake of thymidine by peripheral blood mononuclear cells (PBMCs) (23). Parthenolide also inhibited thymidine uptake by PBMCs. Both parthenolide and the extracts were cytotoxic to the PBMCs and synovial cells thus, the anti-inflammatory effects of feverfew may be secondary to cytotoxicity. These results reflect those of previous researchers who found parthenolide and other sesquiterpene lactones to be cytotoxic to cultures of human fibroblasts, human laryngeal carcinoma cells, and human cells transformed with simian virus 40 (24). 

Collier HO J, Butt NM, McDonald-Gibson WJ, S aeed S A. Extract of feverfew inhibits prostaglandin biosynthesis. Lancet 1980 2 922-923. 

Pharmacology In vitro studies have shown decreased histamine release from mast cells, inhibition of prostaglandin and leukotriene formation, and decreased TNF expression. The fresh leaves of feverfew are thought to have prophylactic value in migraine. Three of five randomized, double-blind, placebo-controlled trials in migraine showed reductions in headache frequency and severity and in nausea. The only well-controlled study of feverfew in rheumatoid arthritis failed to show clinical benefit. 

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