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

• 来源期刊: 中国药理学报
• 关键词: Tanacetum parthenium Feverfew parthenolide sesquiterpenes lactones stomach fundus ileum serotonin antagonist migraine
• 年，卷（期）: 2000,（12）
• 页码范围: 1106-1114
• 页数: 9页
• 语种: 英文

摘要

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: Isomeaic 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 Feveffew 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 ℃ and 75 % relative humidity and the expe nments were reperepeated. In another set of experiments rats were fed with 20 rog/kg Feverfew powder (equivalent to a human dose of 500 pg parthenolide per day) for 30 d or were ip injected with parthenolide (23.4 μg/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. Feveffew was specially formulated and tested for stability under accelerated conditions. RESULTS: Parthenolide (1 × 10-5 mol/L) non-competitively antagonised the effects of d-fenfluramine but had nosignificant effect on 5-HT2B and 5-HT2A receptors in rat fundus and ileum at 30 ain which turned significant on increasing the incubation time to 1.5 h, in rat fundus. Parthenolide (5 × 10-5 mol/L) followed the same trend.. However, Feverfew extract (1 × 10-5 mol/L) potently and directly blocked 5-HT2B and 5-HT2A receptors and neuronally released 5-HT. At 5 × 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 undegraded and degraded Feveffew powder and injected ip with parthenolide. Feverfew powder was more effective than any of its extracts or pure parthenolide. CONCLUSION: Feveffew 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 Feveffew powder containing less contents of parthenolide no builtup antiserotonergic responses were observed after one month. This ascertains that Feverfew should be dispensed in a properly stabilized form wherein its partbenolide content is not degraded to less than 90 % of the original content.