Network pharmacology analysis of integration of dietary plant-derived natural flavonoids and gut microbiota for the treatment of Polycystic Ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder manifested by hyperandrogenism, ovulatory dysfunction, and systemic metabolic dysregulation. While the ‘gut-diet’ axis offers potential therapeutic avenues, the synergistic molecular mechanisms integrating dietary flavonoids and gut microbiota remain elusive. This study employed a comprehensive network pharmacology approach, coupled with molecular docking validation, to decode the tripartite interaction network of ‘Dietary Flavonoids–Gut Microbiota–Host Targets.’ Our analysis identified Luteolin and Quercetin as critical bioactive mediators that interact with specific gut microbial taxa. Topological network analysis revealed that these compounds exert the effects by targeting pivotal nodes—AKT Serine/Threonine Kinase 1 (AKT1), Epidermal Growth Factor Receptor (EGFR), and Insulin Receptor (INSR). Functional enrichment analysis further demonstrated that these targets converge on the Mitogen-Activated Protein Kinase (MAPK) signalling pathway. Conclusively, this study establishes a systematic theoretical framework for the integrated management of PCOS. Future research should prioritize experimental validation and clinical translation of the findings to develop personalized precision medicines targeting the gut-metabolic axis.