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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

5-Hydroxytryptamine-inhibiting property of Feverfew: role of parthenolide content.

AIM: To study the mechanism of antimigraine activity of Tanacetum parthenium (Feverfew), its extracts and parthenolide, a component of Feverfew, by observing their effect on 5-HT storage and release, and stimulation of 5-HT2B and 5-HT2A receptors. Also to standardize a dosage form of Feverfew with respect to its parthenolide content. METHODS: Isometric responses to 5-HT and an indirect acting serotonergic, d-fenfluramine, were obtained on rat fundus and ileum. In one set of experiments the effect of dichloromethane extract of Feverfew and parthenolide was observed on the above. The extract was then thermally degraded upto 10%, 23%, and 33% with respect to its parthenolide content by keeping at 60 degrees C and 75% relative humidity and the experiments were repeated. In another set of experiments rats were fed with 20 mg/kg Feverfew powder (equivalent to a human dose of 500 micrograms parthenolide per day) for 30 d or were i.p. injected with parthenolide (23.4 micrograms/day) for 7 d. In the same set of experiments one group of rats were fed with 15% and 77% degraded Feverfew powder in the same dose as mentioned above. After 30 days the effects of the above were observed on 5-HT and d-fenfluramine. Feverfew was specially formulated and tested for stability under accelerated conditions. RESULTS: Parthenolide (1 x 10(-5) mol/L) non-competitively antagonised the effects of d-fenfluramine but had no significant effect on 5-HT2B and 5-HT2A receptors in rat fundus and ileum at 30 min which turned significant on increasing the incubation time to 1.5 h, in rat fundus. Parthenolide (5 x 10(-5) mol/L) followed the same trend. However, Feverfew extract (1 x 10(-5) mol/L) potently and directly blocked 5-HT2B and 5-HT2A receptors and neuronally released 5-HT. At 5 x 10(-5) mol/L the extract potently and irreversibly blocked the above. Both parthenolide and Feverfew extract showed a time-dependency in their action. The extract when degraded thermally upto 10% could significantly block the 5-HT receptors and neuronal release of 5-HT, however, on further degradation it lost its inhibitory capacity markedly. Similar results were observed in rats fed orally with undergraded and degraded Feverfew powder and injected i.p. with parthenolide. Feverfew powder was more effective than any of its extracts or pure parthenolide. CONCLUSION: Feverfew powder is more potent than any of its extract or parthenolide alone in its antiserotonergic activity. Degraded Feverfew extracts show a marked decrease in their antiserotonergic activity. With thermally degraded Feverfew powder containing less contents of parthenolide no built-up antiserotonergic responses were observed after one month. This ascertains that Feverfew should be dispensed in a properly stabilized form wherein its parthenolide content is not degraded to less than 90% of the original content.[1]


  1. 5-Hydroxytryptamine-inhibiting property of Feverfew: role of parthenolide content. Mittra, S., Datta, A., Singh, S.K., Singh, A. Acta Pharmacol. Sin. (2000) [Pubmed]
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