5-hydroxytryptamine-inhibiting property of Feverfew: role of parthenolide content

AIM: To study the mechanism of antimigraine activity of Tanacetum partheniu m (Feverfew), its extracts and parthenolide, a component of Feverfew, by ob serving 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 r espect to its parthenolide content. METHODS: Isometric responses to 5-HT an d an indirect acting serotonergic, d-fenfluramine, were obtained on rat fun dus and ileum. Tn one set of experiments the effect of dichloromethane extr act of Feverfew and parthenolide was observed on the above. The extract was then thermally degraded upto 10 %, 23 %, and 33 % with respect to its part henolide content by keeping at 60 degreesC and 75 % relative humidity and t he experiments were repeated. In another set of experiments rats were fed w ith 20 mg/kg Feverfew powder (equivalent to a human dose of 500 mug parthen olide per day) for 30 d or were ip injected with parthenolide (23.4 mug/day ) for 7 d. In the same set of experiments one group of rats were fed with 1 5 % 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-fenflura mine. Feverfew was specially formulated and tested for stability under acce lerated conditions. RESULTS: Parthenolide (1x10(-5) mol/L) non-competitivel y antagonised the effects of d-fenfluramine but had no significant effect o n 5-HT2B and 5-HT2A receptors in rat fundus and ileum at 30 min which turne d significant on increasing the incubation time to 1.5 h, in rat fundus. Pa rthenolide (5 x 10(-5) mol/L) followed the same trend. However, Feverfew ex tract (1x10(-5) mol/L) potently and directly blocked 5-HT2B and 5-HT2A rece ptors and neuronally released 5-HT. At 5 x 10(-5) mol/L the extract potentl y and irreversibly blocked the above. Both parthenolide and Feverfew extrac t showed a time-dependency in their action. The extract when degraded therm ally upto 10 % could significantly block the 5-HT receptors and neuronal re lease of 5-HT, however, on further degradation it lost its inhibitory capac ity markedly. Similar results were observed in rats fed orally with undegra ded and degraded Feverfew powder and injected ip with parthenolide. Feverfe w powder was more effective than any of its extracts or pure parthenolide. CONCLUSION: Feverfew powder is more potent than any of its extract or parth enolide alone in its antiserotonergic activity. Degraded Feverfew extracts show a marked decrease in their antiserotonergic activity. With thermally d egraded Feverfew powder containing less contents of parthenolide no built-u p antiserotonergic responses were observed after one month. This ascertains that Feverfew should be dispensed in a properly stabilized form wherein it s parthenolide content is not degraded to less than 90 % of the original co ntent.