Unraveling the therapeutic mechanisms of placenta hominis for polycystic ovary syndrome through network pharmacology, molecular docking, and experimental validation.

This study employed an integrated strategy of network pharmacology, molecular docking, and in vitro assays in KGN cells to explore the mechanisms of action of Placenta Hominis (PH) in Polycystic Ovary Syndrome (PCOS). We hypothesized that PH (which contains bioactive compounds such as steroid hormones and peptides) exerts its therapeutic effects against PCOS through a multi-target mechanism. Potential targets of PH- and PCOS-related genes were identified in public databases. After network analysis and filtering by interaction confidence scores, 289 common targets were retained. Subsequent protein-protein interaction (PPI) analysis identified 30 core targets, including sex hormone-related (AR, ESR1, INS) and apoptosis-related (TP53, TNF, NFκB1, BCL2) proteins. Enrichment analyses (GO and KEGG) suggested that PH may exert therapeutic effects primarily through pathways such as endocrine resistance and estrogen signaling. Molecular docking suggested stable binding between key PH compounds and the core targets, and molecular dynamics simulations supported stable binding between progesterone and the apoptosis-related proteins (TP53, TNF, NFκB1, BCL2). In cellular experiments using DHT-induced KGN cells, PH treatment promoted proliferation, reduced oxidative stress, and suppressed apoptosis compared to the DHT only control. Mechanistically, these effects involved the modulation of sex hormone- and apoptosis-related pathways. In conclusion, this multi-method study demonstrates that PH can mitigate PCOS progression by regulating central pathways linked to hormonal balance and apoptosis, providing a theoretical basis for future preclinical in vivo studies and further investigation into potential clinical applications.