Antigestagenic activity of Ixora finlaysoniana in rat

Oral administration of crude ethanolic extract of the serial parts of Ixora finlaysoniana Wall. ex G. Don to adult female rats at 250 mg/kg dose on days 1-5 or 1-7 post-coitum prevented pregnancy in 100% rats. The extract was also effective when administered on days 1 or 1-3 post-coitum, but the minimum effective dose increased with decreased duration of administration and was 1000 mg/kg and 500 mg/kg, respectively, in the two schedules. At lower doses, a significant reduction in implantation number and increased post-implantation resorption rate were observed in all the schedules. Almost complete resorption of all implantations was observed after administration of 1000 mg/kg dose of the extract during the peri-implantation period. A slight acceleration in tubal transport rate of embryos and delay in blastocyst formation were observed in rats treated postcoitally with the single anti-implantation dose of the extract. Significantly fewer embryos were recovered after their entry into the uterus. Except in one rat receiving 250 mg/kg dose of the extract on days 1-5, in which one apparently normal zona-free blastocyst was recovered from the uterus, uterine flushings of none of the nonpregnant animals contained any unimplanted embryos by day 10 post-coitum. In immature rat bioassay, the extract was found to possess estrogenic activity as evidenced by dose-dependent increase in uterine weight and cornification of the vaginal epithelium at doses ranging from 50-1000 mg/kg. At the 500 and 1000 mg/kg doses, it also induced premature opening of the vagina. Taking 100% increase in uterine weight as the parameter, the extract was found to be about 1.6X10(5) times less estrogenic than ethinylestradiol. The extent and duration of estrogenic responses exerted by single contraceptive dose of the extract were also markedly lower than that induced by ethinylestradiol. The extract was devoid of any estrogen antagonistic or synergistic activity and did not affect ovarian prenidatory estrogen or progesterone synthesis. The findings indicate that the extract at its contraceptive dose a) exerts a differential estrogenic response at the fallopian tube and the uterine levels, b) does not appear embryocidal, but causes slight asynchrony in development and tubal transport rate of pre-implantation embryos, which together with their loss through vagina after entry into the uterus, due to estrogenic action of the extract, might contribute to its anti-implantation action, and c) its anti-implantation and post-implantation resorptive actions are not mediated via altered ovarian function.