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  • Title: Antigestagenic activity of Ixora finlaysoniana in rat.
    Author: Singh MM, Chowdhury SR, Kulshreshtha DK, Kamboj VP.
    Journal: Contraception; 1993 Aug; 48(2):178-91. PubMed ID: 8403914.
    Abstract:
    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. Colony-bred immature (25-35 gm) and adult (180-220 gm) Sprague-Dawley rats were administered orally an 85% ethanolic extract of powdered aerial parts of Ixora finlaysoniana suspended in distilled water. The extract prevented pregnancy in 100% of rats at a dose of 250 mg/kg on days 1-5 or 1-7 post coitus. However, 1000 mg/kg and 500 mg/kg doses were required to achieve complete contraception increasing with decreased duration of administration of the extract. At sub contraceptive doses, a significant reduction in implantation and a marked increase in post implantation resorption rate were observed in all the schedules. Almost complete resorption of all implantations was observed at 1000 mg/kg dose of the extract administered on days 5-7 post coitus. Single oral anti implantation dose (1000 mg/kg) of the extract administered within 24 hours of coitus induced slight acceleration of tubal transport of embryos. Fewer extract-treated rat embryos were recovered from the Fallopian tubes compared with controls on days 4 and 5 to (p 0.01). 1 normal zona free blastocyst was also recovered from the uterine flushings of a rat treated with a 250 mg/kg dose on days 1-5 post coitus, but uterine flushings of none of the 43 remaining nonpregnant rats treated with the various doses on days 1, 1-3, 1-5, or 1-7 yielded any unimplanted embryos by day 10 post coitus. Doses ranging from 50 to 1000 mg/kg once daily for 3 consecutive days induced a dose-independent increase in uterine weight (p 0.001) vs. controls and cornification of the vaginal epithelium in bilaterally ovariectomized rats. Premature opening of the vagina was observed only at 500 and 1000 mg/kg doses. A single oral contraceptive dose of 1000 mg/kg induced a significant increase (p 0.05) vs. the control group in uterine weight and premature opening of the vagina and 40-60% vaginal cornification in all treated rats. In comparison, a single oral contraceptive dose (1.5 mg/kg) of ethinyl estradiol induced stronger and longer estrogenic responses; uterine weight gain at all time intervals was significantly more than with the extract.
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