Effects of Combretum micranthum against menopause-related osteoporosis based on ADMET, network pharmacology, and experimental validation

Abstract

Low bone density is a defining feature of osteoporosis. Combretum micranthum is traditionally used in Burkina Faso against osteoporosis. This research sought to assess the effect of Combretum micranthum (AECM) on an osteoporosis model induced by ovariectomy and to conduct molecular docking and ADMET screening of the identified potentially active compounds from the AECM leaves by using in silico techniques.

A pharmacology network was constructed to identify genes corresponding to active compound targets. Networks of compound targets and protein-protein interactions were constructed using Cytoscape software. To evaluate C. micranthum's effect on the ovariectomized rats, a sham-operated group and some ovariectomized groups were treated with distilled water or with AECM and estradiol valerate.

In the in silico study, the extract compounds like myricetin and rhamnazin predicted good pharmacokinetics and low toxicity, with LD₅₀ over 2000 mg/kg bw. C. micranthum extract increased significantly (p < 0.001) femoral calcium and phosphorus, and decreased the urinary calcium and phosphorus compared to the group treated with distilled water. It also reduced oxidative stress and improved lipid profiles. Moreover, the histological report on the femurs of the treated rats showed a correction of the lesions caused by ovariectomy. Myricetin's interaction with hypoxia-inducible factor-1α (HIF-1α), with –95.0929 energy, could have therapeutic potential for osteoporosis.

C. micranthum promoted bone health, offering a promising alternative to conventional osteoporosis treatments with fewer side effects.