Effects of estrogen-like plant compounds on the vaginal epithelium pituitary, adrenal glands, and uterus of rats

Abstract

Plant species with recognized estrogenic activity and widely used by Brazil’s female population to prevent the unpleasant symptoms of menopause were investigated in this work to demonstrate if constituents of taro-inhame ( Colocasia esculenta), cumaru ( Dipteryx odorata), and camapu ( Physalis angulata) have the ability to mimic or interfere with the action of estrogens. Moreover, their potential use as natural sources of estrogen-like substances for hormone replacement therapy was evaluated. (a) In vivo pharmacological assays were conducted to determine the estrogenic effects of D. odorata isoflavone-rich extract, P. angulata physalin-rich extract, and C. esculenta flavonoid glycoside-rich fraction (FG) on endocrine glands and reproductive organs of female rats at three different stages of the life cycle. The protocols consisted of uterotrophic assays and cytological evaluation of vaginal smears to detect mucosa cell alterations correlated with changes in hormone levels in each phase of the estrous cycle of female rats. The results indicated that C. esculenta FG exhibited estrogenic activity in prepubescent, pubescent, and adult ovariectomized female rats, while D. odorata isoflavones only promoted a weight increase in the pituitary gland of prepubescent rats after prolonged treatment and P. angulata physalins induced a weight increment in the adrenal glands of ovariectomized rats. Additionally, C. esculenta exerted a significant effect on the opening of the vaginal canal in prepubescent rats and on vaginal epithelium. Prolonged treatment of ovariectomized rats with FG altered the proportion of different types of vaginal epithelial cells in these animals, suggesting an interference of FG with estrogen levels. Colocasia esculenta FG induced hypertrophy of the uterus and pituitary in ovariectomized rats similar to estradiol. To elucidate the mechanism of action of FG, its effects were compared to those of estradiol and of the selective estrogen receptor modulator raloxifene. The results suggest that the efficacy of C. esculenta FG is mediated by binding to selective estrogen receptors present in each organ and that raloxifene inhibits the mechanism of action of FG in the same way as it inhibits the effects of estradiol. The overall findings indicate that C. esculenta FG mimics the action of estrogens, with reduced harmful effects on specific tissues. Impact statement The results of this work provide preliminary evidence that ovariectomized rats display the vaginal smear cells typical of the estrous phase of mature rats after long-term ingestion of Colocasia esculenta flavonoid glycosides. Moreover, the treatment caused beneficial effects on endocrine and reproductive organs compared to estradiol. The animals did not exhibit significant body weight alterations among the groups, demonstrating the maintenance of standard metabolism and energy balance. The overall findings obtained with the rat model of menopause highlight the importance of dietary consumption of C. esculenta constituents as potential selective estrogen receptor modulators and suggest that they may prevent some of the metabolic disorders related to estrogen deficiency.