Effets des phyto-œstrogènes du duramen de Pterocarpus soyauxii Taub. (Fabaceae) sur quelques symptômes de la ménopause chez le rat Wistar

Abstract

The use of hormonal treatment of menopause (HRT) to reduce menopausal disorders is less and less solicited because of its limitations and side effects leaving room for the search of therapeutic alternatives. Phytoestrogens (PEs); estrogen receptor agonists are increasingly used as an alternative treatment to HRT. However, their estrogenic activities are known to disrupt the reproductive function of women of childbearing age who are exposed to them. The main objective of this work was to evaluate the effects of phytoestrogens from Pterocarpus soyauxii heartwood on some menopausal symptoms in rats. To achieve this objective, a series of pharmacological tests were performed. The first test consisted in evaluating the estrogenic effects of the aqueous extract of the duramen of Pterocarpus soyauxii in the rat during a classical 3-day uterotrophic test. The second test was carried out in order to investigate the effects of the aqueous extract of the duramen of Pterocarpus soyauxii on some menopausal symptoms in the rat during a 28 days treatment. The third test was performed to evaluate the effects of the aqueous extract of Pterocarpus soyauxii heartwood on some parameters of the reproductive function in normal rats. A fourth test was carried out in order to establish an acute and subchronic toxicity profile of the aqueous extract of P. soyauxii heartwood. A last pharmacological test consisted in evaluating the in vitro antioxidant power and the qualitative and quantitative phytochemical composition of the aqueous extract of Pterocarpus soyauxii heartwood. The results showed that the aqueous extract of P. soyauxii at doses of 100, 200 and 300 mg/kg induced estrogenic activity marked by a significant increase in the size of the vaginal epithelium, uterine protein level and mammary acini size in the uterotrophic test. In the menopausal model, P. soyauxii at doses of 200 and 300 mg/kg significantly increased the size of the vaginal epithelium and induced stratification and cornification of the vaginal epithelium. At the same doses, aqueous extract of P. soyauxii induced antidepressant, anxiolytic and antiamnesic activity and prevented neuronal degeneration. This extract also induced an anti- osteoporotic activity marked by a reduction on histological sections of femur and tibia of the density of resorption lacunae, an increase compared to Ovx animals receiving distilled water of bone density, bone protein level, reduced glutathione and normalization of serum levels of bone metabolism parameters (calcium, phosphorus and alkaline phosphatase). On risk factors for postmenopausal cardiovascular disorders, P. soyauxii at doses of 200 and 300 mg/kg reduced weight gain and relative abdominal fat mass, corrected dyslipidemia, reduced intima/media ratio on aortic sections. In normal rats, at 200 and 300 mg/kg reduced the relative mass of the ovary and the number of total ovarian follicles and altered the duration of estrous cycle phases. The results of the toxicological studies showed that P. soyauxii has a lethal dose 50 higher than 5000 mg/kg in acute toxicity and did not induce in subacute toxicity histological and biochemical alterations at the level of liver and kidney at the doses of 200 and 400 mg/kg. The qualitative phytochemical analyses of the extract allowed to highlight the presence of bioactive compounds such as alkaloids, saponins, flavonoids. The LC-MS analysis revealed the presence of molecules such as linoleic acid, mono (2-ethylhexyl) phthalate and 3',5'- dimethoxy-4-stilbenol. The extract also showed in vitro antioxidant activity against DPPH, ABTS and FRAP. The present results would justify the empirical use of P. soyauxii for the management of menopausal disorders but its use should be limited in pre-menopausal women with the desire to have a child.