Feverfew: Background. Actions

Historical Note

Feverfew has been used for centuries in Europe to treat headaches, arthritis and fever and used as an emmenagogue and anthelmintic agent. In the 1970s it was ‘rediscovered’ by the medical establishment and subjected to clinical studies, which produced encouraging results that suggested feverfew was an effective prophylactic medicine for migraine headache.

Other Names

Altamisa, bachelor’s button, camomile grande, featherfew, featherfoil, chrysanthemum parthenium, mutterkraut, matrem, tanaceti parthenii herba/folium

Botanical Name / Family

Tanacetum parthenium (family [Asteraceae] Compositae)

Plant Part Used

Leaf

Chemical Components

The leaves and flowering tops contain many monoterpenes and sesquiterpenes as well as sesquiterpenes lactones (chrysanthemolide, chrysanthemonin, 10-epi-canin, magnoliolide and parthenolide), reynosin, santamarin, tanaparthins and other compounds. Until recently, the sesquiterpene lactone parthenolidewas thought to be the major biologically active constituent. However, in vitro and in vivo research suggests others are also present.

Clinical note – Natural variations in parthenolide content

The amount of parthenolide present in commercial preparations of feverfew leaves varies significantly, with some exhibiting levels as high as 1,7 % dry weight and others as low as 0.01% to non-detectable. The study by Cutlan et al measured the parthenolide content in plants produced from seeds taken from over 30 different sources and germinated under identical conditions. According to this study, feverfew collected from the wild and distributed by botanical gardens or US Department of Agriculture seed banks yielded plants with the highest mean parthenolide value, and plants with yellow leaves also had significantly higher parthenolide levels than those with green leaves.

Main Actions

ANTI-INFLAMMATORY AND ANALGESIC

Several in vivo studies have identified anti-inflammatory and antinociceptive activity for feverfew extracts and parthenolide. When feverfew extracts were orally administered, or pure parthenolide was injected IP, significant dose-dependent anti-inflammatory and antinociceptive effects were observed in animal models. Similarly, when feverfew extracts and parthenolide from Tanacetum vulgare was administered orally in a rat model, gastric ulcer index was significantly reduced.

The mechanisms responsible for these effects are not well elucidated. Jain and Kulkarni (1999) demonstrated that the antinociceptive effect was not mediated through the opiate pathway and was not associated with sedation. In regards to the anti-inflammatory effect, several mechanisms appear to be responsible.

Two in vitro studies have found evidence of COX and lipoxygenase inhibition, while other tests reveal no effect on COX. Inhibition of phospholipase A2 has also been suggested. Direct binding and inhibition of l-kappa B kinase beta, an important subunit involved in cytokine-mediated signalling, has been demonstrated for parthenolide in test tube studies. Parthenolide also inhibits NO production, an important regulator and inducer of various inflammatory states. More recently, results from an in vivo study confirm that parthenolide inhibits proinflammatory cytokine responses, although the authors propose that proinflammatory mediators including chemokines (MIP-2), plasma enzyme mediators (complement, kinin and clotting systems) and lipid mediators (COX, PG, platelet-activating factor) are also likely to be involved.

The essential oil constituent of feverfew, chrysanthenyl acetate, inhibits PG synthetase in vitro and also seems to possess analgesic properties.

ANTISPASMODIC

The results from several in vitro studies generally indicate that feverfew decreases vascular smooth muscle spasm.

INHIBITS SEROTONIN RELEASE AND BINDING

Parthenolide and several other sesquiterpene lactone constituents inhibit serotonin release but do not bind to 5HT1 receptors, according to in vivo data. Some tests with 5HT2A receptors show parthenolide is a low-affinity antagonist, whereas other tests found no effect on 5HT2A or 2b receptors. Feverfew extract potently and directly blocked 5HT2A and 2B receptors and neuronally released 5HT, suggesting that feverfew powder or extracts are more effective than isolated parthenolide.

Other Actions

INHIBITS PLATELET AGGREGATION

Evidence is contradictory as to whether feverfew inhibits platelet aggregation. Several test tube studies and animal models have observed inhibition of platelet aggregation. However, no significant effects were seen in a clinical study of 10 patients receiving feverfew.

MAST-CELL STABILISATION

Tests with rat mast cells indicate that feverfew extract inhibits histamine release, but the mechanism of action is different to cromoglycate and quercetin.