草药雷公藤中的雄性抗生育有效成分

经雄性大鼠抗生育试验证明，无毒性剂量的雷公藤提取物可导致不育，停药后恢复；临床试用１／３～１／４常规量的雷公藤提取物可使男病人不育。进行了植化分离和动物筛选，获得了６个雄性抗生育有效环氧二萜类化合物：雷藤甲素、雷藤乙素、雷醇内酯、雷藤氯内酯醇，１６－羟雷藤甲素以及Ｔ７／Ｔ１９，均鉴定了结构。它们的结构和作用均类似，因而估计为某母物质的植物代谢产物。对雷藤氯内酯醇进行了较深入的研究，表明其作用部位为晚期精子细胞及附睾精子。几个化合物的不良反应主要是大剂量（５．５～１１．５倍抗生育有效量）时有一定的免疫抑制作用。优选对免疫影响最小的化合物及寻找更佳的类似物，为今后研究的重点。

Male antifertility compounds isolated from Tripterygium wilfordii

Tripterygium wilfordii Hook. f. (Celastraceae) has been used in traditional Chinese medicine for more than 2 000 years. Worldwide interest arose from reports on the antifertility effects of an extract from the plant on male rats as well as in men taking it to treat their rheumatoid arthritis and an international effort aimed at the bioassay-directed sub-fractionation of materials extracted from the plant was organized. To date, more than 400 samples (compounds/components) have been assayed and a series of 6 active male antifertility diterpene epoxides were isolated with their structure identified: T4 (tripchlorolide),T9 (triptolidenol), T13 (triptolide), T15 (tripdiolide), T7/T19(structure unpublished) and L2 (16-hydroxytriptohde). Among them T4 and L2 are new substances. When given orally for 7～8 weeks to male SD rats, the ED95 daily doses for T4,T7/T19,T9,T13 and T15 were 50, 400,100, 30 and 25 μg/kg, respectively. The results were similar :the fertility dropped to 0～10% of the control,and first the motility and then the concentration of spermatozoa in the cauda epididgmis were dramaticallg decreased. No discermible changes were seen in the testis and the histology of important somatic organs was unaltered. Their main target cells appeared to be epididymal spermatozoa and metamorphosing spermatids. It was shown that all these compounds suppressed the immune function when large doses were employed. Immuno-suppression is an important weakness for an antifertility agent, however,if the immuno-suppressive dose of a drug is much higher than its fertility-suppression dose,it could yet be regarded as a safe antifertility agent. Recently it was found that the immuno-suppressive effect of T7/T19 was much less than those of the other compounds. It is concluded that compunds isolated from T. wilfordii represent a new lead in the search for male antifertility agents,but their future will depend upon the results of meticulous safety evaluation.