In Vivo Investigation of Root Extract of <i>Paederia foetida</i> Linn. on the Reproductive Functions of Female Albino Mice and In Silico Validation With Human Estrogen Receptors

Ethnic Mising women of northeast India uses the dried root of Paederia foetida Linn. for fertility regulation. However, there is no scientific literature regarding female reproductive concerns so far. Therefore, this study was undertaken to know the phytocompounds present in the root of P. foetida and investigate the effect of P. foetida on the estrous cycle, ovarian, and uterine histoarchitecture. Methanolic root extract (MRE) was prepared at the doses 250 and 500 mg/kg bw (compared to 17β-estradiol as a reference drug) and was tested in ovary-intact mice for 21 days. MRE at 500 mg/kg bw-treated mice resulted in degenerative ovarian histoarchitecture with a significant increase (p < 0.05) in atretic follicles and a significant decrease (p < 0.05) in a number of endometrial gland and disruptive reproductive hormones. Compounds like stigmasterol, having profound antifertility agents, were found in the GC-MS analysis. As per molecular docking, the phytocompounds that showed the highest binding affinity were γ-sitosterol (-11.25 kcal/mol) and ergosterol (-12.92 kcal/mol) against human estrogen receptor alpha and beta (hERα and hERβ), respectively. This study is the first-ever report of P. foetida roots extract on reproductive parameters and compounds of P. foetida showing binding affinity with hER. This study provides scientific evidence that supports the traditional usage of P. foetida Linn. for fertility regulation, which will further help in the standardization and development of drugs for fertility control.