Pterocarpus soyauxii (Fabaceae) aqueous extract to prevent neuropsychiatric disorders associated with menopause by triggering ROS-dependent oxidative damage and inhibiting acetylcholinesterase, GABA-transaminase, and monoamine oxidase A: In vitro, in vivo, and in silico approaches

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.