Feverfew belongs to the family Asteraceae and in modern botanical literature is referred to by Tanacetum parthenium. It is an aromatic perennial that grows from 20 to 60 centimeters tall, has greenish yellow two- to five-lobed leaves and flowers that resemble those of chamomile. It is a native of Europe and was naturalized in North and South America in the nineteenth century. It should be noted that there are at least three different chemotypes of this species, two of which do not contain the purported active principle parthenolide.
The most studied and abundant group of active compounds in feverfew are sesquiterpene lactones, the principle one being parthenolide which makes up 85% of the total sesquiterpene content of the leaves. In addition there are lipophilic flavonols, tanetin and quercetagetin and water-soluble flavone glycosides apigenin 7-glucuronide, luteolin 7-glucuronide, luteolin 7-glucoside and chrysoeriol 7-glucuronide.
In 1983 the City of London Migraine Clinic reported the efficacy of feverfew in treating migraine headaches. In subsequent studies in England, out of the 270 migraine sufferers surveyed 70% of respondents reported a decrease in frequency and severity of attacks. A larger study done at the University Hospital in Nottingham, UK assessed migraine prophylaxis in a 4-month, randomized, double blind, placebo-controlled crossover study. Dried feverfew powder in capsules equivalent to two medium sized leaves showed 24% reduction in the number and severity of headaches and showed a significant reduction in nausea and vomiting accompanying the attacks.
Recently, in 1997 a double-blind, placebo-controlled, cross-over study in Israel demonstrated that 100 mg of dried feverfew leaves administered in capsules reduced the intensity of migraine headaches as well as ameliorated symptoms of nausea, vomiting and the sensitivity to noise and light. However, a 1996 Dutch study carried out using a 90% v/v ethanol extract of feverfew containing 0.35% of parthenolide to be ineffective as a prophylactic in treating migraine headaches. Contrary to studies in Israel that demonstrated migraine prophylaxis using feverfew leaves, the Dutch study did not exhibit any pharmacological activity in the alcoholic extract of the herb in spite of parthenolide being present in samples tested in both studies. Therefore, there is reason to believe that one or more compounds other than parthenolide present in the raw leaf sample, but absent in the alcoholic extract, may be the pharmacologically active agent(s). Also, there are many other plant species that contain parthenolide but none have demonstrated migraine prophylaxis.
Mechanism of Action:
For many years it has been thought that parthenolide has been responsible for feverfew’s anti-migraine actions. Current research suggests a more complicated picture; while parthenolide may contribute to feverfew’s efficacy, there appear to be other components that also are involved. For example, our work has demonstrated that parthenolide is modestly active at a type of serotonin receptor thought to be important in the actions of prophylactic anti-migraine drugs. This modest activity could account for part of feverfew’s effectiveness, but by no means all of it. Either parthenolide is also active at targets other than the receptor studied, or compounds in addition to parthenolide are involved or both. Using extracts of feverfew, serotonin receptor activity appears to be due to fractions other than those containing most of the parthenolide.
Noteworthy biochemical actions of feverfew that have been discovered include the following: Feverfew blocks prostaglandin synthesis. Since prostaglandins are known to cause inflammatory reactions, some of feverfew’s effectiveness may be due to this effect. Changes in blood platelets have long been used as models for effects produced by anti-migraine drugs. Since feverfew can interfere with platelet aggregation and can block serotonin release from platelets, there is some thought that serotonin effects such as these may be involved in feverfew’s mechanism of action.
There are many additional biochemical effects known for feverfew. Some of these may also play a role in the plant’s clinical efficacy. The bottom line, however, is that we don’t know how feverfew works.
Considerably more research is required to unravel the active mechanisms, to better understand which compounds, including pathenolide are involved, and in further appreciating differences in clinical effectiveness due to use of different strains of feverfew.
Its use in pregnancy should be avoided as it does cause uterine contractions. There is insufficient information for its use during lactation.
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