Molecular Docking, Contraceptive Property and Histopathological Changes in Experimental Models by Digitaria exilis Grain Extract via Interference with Steroidogenesis at Ovarian Level

The use of Digitaria exilis in traditional medicine for contraception has been scientifically validated without a report on the mechanism of its possible risk to women's fertility. Therefore, this study evaluated the potential mechanism of contraceptive property of aqueous grain extract of Digitaria exilis (AGEDE) in female Wistar rats using molecular docking and histopathological analysis. Twenty female rats were grouped into four (n=5). Group A served as control while groups B-D received (50, 100, and 200 mg/kg BW) of AGEDE for fourteen days. Serum and ovary levels of some reproductive biomarkers and histopathology and molecular docking analysis were conducted. Progesterone, FSH, LH, estrogen, and prolactin levels were altered at different AGEDE dosal levels in the serum and ovary of the animals. The histoarchitecture of ovarian and uterine tissues was altered by AGEDE, with severe infiltration of inflammatory cells, degenerated luteal cells, loosed ovarian stroma with severe vascular congestion, as well as degenerated endometrial glands with distorted hyperplasia, endometrium layer with deranged vascularization and severely fibrotic endometrium, respectively. Phytochemical analyses of AGEDE identified flavonoids, saponins, and tannins. Molecular docking analysis of previously documented compounds with 3β-hydroxysteroid dehydrogenase (3βHSD) revealed that ethylacetate had the highest docking score (-4.69227982), followed closely by 2,5-dimethylhydrazine (-4.61382103), while pyrazine (-3.80633807) had the least binding affinity. AGEDE demonstrated toxicity to the female reproductive organs via alteration and/or interference with steroidogenesis at the molecular, hormonal, enzymic, uterus, and ovarian levels. These interferences may affect fertility, conception, and pregnancy. Therefore, Digitaria exilis may be explored as a fertility-controlling agent.