RESUMEN
Pterocarpus soyauxii (PS) is traditionally used in Cameroon medicine to alleviate postmenopausal symptoms. Previous research has shown that it has tissue-selective potential and estrogen-mimetic effects on vaginal atrophy. Phytoestrogens like 7-O-acetyl formononetin, khrinone A, and 3',5'-dimethoxy-4-stilbenol were found in its water extract by UHPLC, but there is no evidence of its effects on neurological disorders linked to post-menopause (ND-PO). The study aimed to investigate the phytochemical profile of PS aqueous extract, assess its neuroprotective potential in rats, and explore possible underlying pathways. We used colorimetric assays to study the phytochemical profile of PS extract. Effects of the extract on behavioral parameters, neuronal signaling, and integrity in an 84-day ovariectomized rat model. Molecular docking was performed to assess the ability of 7-O-acetyl formononetin, an isoflavone contained in PS, to cross the BBB and its binding affinity to the active sites of AChE, MAO-A, and GABA-T. Besides, the anti-AChE/BChE, antioxidant, and anti-inflammatory effects of PS were assessed by in vitro tests. PS aqueous extract contains polyphenols (656.58 ± 9.18 mgEAG/100gMS), flavonoids (201.25 ± 5.52 mgEQ/100gDW), and tannins (18.42 ± 1.25 mg/100gDW). It slows down anxiety, depressive disorders, cellular disorganization, and neuronal death in the hippocampus, dentate gyrus, and neocortex. In silico modeling was a powerful tool to assess the 7-O-acetylformononetin's ability to cross the BBB and strongly bind and inhibit AChE, MAO-A, and GABA-T. Thus, by combining GABAergic, cholinergic, and serotoninergic modulation, PS aqueous extract also possesses remarkable anti-AChE/BChE in vitro and induces antioxidant and anti-inflammatory potential in macrophages. Such estromimetics, antioxidant, anti-inflammatory, cholinergic, and monoaminergic modulators represent promising activities to develop neuroprotective drugs with optimal therapeutic profiles for menopausal women.
RESUMEN
Phytoestrogens are used to ease postmenopausal symptoms, a property probably due to estrogenic and antioxidant effects. Pterocarpus soyauxii (P. soyauxii) is empirically used in Cameroon to treat among others primary and secondary amenorrhea. The aim of this study is to evaluate estrogenic and antioxidant activities of P. soyauxii heartwood aqueous extract in bilateral oophorectomized Wistar rats. Firstly, a characterization of the extract was carried out. For that, flavonoids, phenols, and tannins levels in P. soyauxii extract were evaluated by colorimetric assays and UHPLC-MS analysis was realized. In vitro antioxidant analysis of P. soyauxii was conducted using DPPH, ABTS, and FRAP assays. Secondly, 2 sets of pharmacologic tests were carried out. The results revealed that P. soyauxii aqueous extract contains, respectively, 229.42 ± 3.62 mg EAG/g, 63.42 ± 2.16 mg EQ/g, and 27.88 ± 0.23 mg ETA/g of polyphenols, flavonoids, and tannins. UHPLC-MS enabled identifying seven components including mono(2-ethylhexyl) phthalate, cembrene, 3',5'-dimethoxy-4-stilbenol, and linoleic acid. DPPH, ABTS, and FRAP assays revealed that P. soyauxii extract possessed a high antioxidant activity with IC50 value of 730.20 µg/mL, 892.90 µg/mL, and 765.75 mEAG/g of extract, respectively. In the uterotrophic assay, P. soyauxii extract induced significant increase of fresh uterine weight, uterine and vaginal epithelial size, and mammary glands differentiation compared to Ovx control. In the postmenopausal model, compared to the sham control, vagina and uterine dystrophies were observed in Ovx rats treated with distilled water. P. soyauxii aqueous extract expressed estrogenic-like effects on vagina and did not affect uterine epithelial height compared with vehicle groups. On the back of these vaginotrophic effects, the extract displayed antiatherogenic properties by reducing (p < 0.001) AI and LDL cholesterol level as compared to Ovx control group. The extract at 200 mg/kg significantly prevented the increase of MDA (p < 0.01) level and decreased nitrites (p < 0.001) and GSH (p < 0.01) levels compared to Ovx rats. These beneficial effects are related at least in part to the presence of compound such as mono(2-ethylhexyl) phthalate, 3',5'-dimethoxy-4-stilbenol, and linoleic acid. Overall, P. soyauxii aqueous extract exhibits estrogenic and antioxidant effects which can inhibit postmenopausal symptoms by providing vaginal stratification, improving lipid profile and insulin sensitivity, and reducing oxidative stress without side effects on the endometrium and mammary gland in 84-day Ovx rats.