Network Pharmacology Integrated Molecular Docking Analysis Identifies Potential Bioactive Compounds in Nigella sativa...

Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting 8%-13% of women of reproductive age. Although Nigella sativa (NS) has been traditionally used for PCOS management, its molecular mechanisms are not fully characterized. This study employed network pharmacology, molecular docking, and molecular dynamics (MD) simulations to identify the key targets and pathways associated with NS bioactives. Venn analysis identified 53 common genes shared between NS-derived phytochemicals and PCOS-associated targets. KEGG and Reactome enrichment revealed 15 significantly enriched pathways (p < 0.05), including ovarian steroidogenesis, insulin resistance, androgen signaling, and inflammatory pathways. Five critical PCOS-related proteins (CYP19A1, CYP11A1, AR, ESR1, and HSD17B1) were selected for docking with major NS phytochemicals. Docking revealed strong binding affinities, with thymoquinone showing the highest binding scores of -8.2 kcal/mol (CYP11A1), -7.6 kcal/mol (CYP19A1), and -7.1 kcal/mol (AR). MD simulation-based flexibility analysis showed that the CYP11A1-thymoquinone complex exhibited higher residue mobility, with RMSF values indicating greater flexibility in the ligand-interacting regions compared to other complexes. These findings suggest that NS exerts therapeutic potential in PCOS through multi-target modulation of steroidogenic enzymes and hormonal pathways, providing a molecular foundation for future experimental validation.