Exploring the Therapeutic Potential of Daidzein in Polycystic Ovary Syndrome Using Network Pharmacology and Molecular Modeling

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Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder characterized by
hyperandrogenism, ovulatory dysfunction, insulin resistance, and chronic low-grade inflammation. Despite
the availability of several therapeutic strategies, most current interventions primarily provide symptomatic
relief and may be associated with adverse effects or limited long-term efficacy. These limitations highlight
the need for safer and more effective multi-target therapeutic agents. Daidzein, a naturally occurring soy
isoflavone, exhibits antioxidant, anti-inflammatory, estrogenic, and insulin-sensitizing properties,
suggesting potential therapeutic relevance in PCOS.
The present study employed an integrated in silico approach comprising network pharmacology, molecular
docking, molecular dynamics simulation, and ADMET profiling to investigate the therapeutic potential of
daidzein against PCOS. Daidzein-associated targets were retrieved from the Comparative Toxicogenomics
Database, while PCOS-related genes were obtained from the GeneCards database. Shared targets were
subsequently analyzed using protein–protein interaction network construction, Gene Ontology enrichment,
and KEGG pathway analyses. Key proteins were further evaluated through molecular docking and molecular
dynamics simulation.
A total of 76 overlapping targets were identified. Network analysis recognized TP53, ESR1, IL6, TNF, EGFR,
and MAPK3 as major hub proteins. Functional enrichment analyses demonstrated significant involvement of
PI3K–Akt, MAPK, TNF, NF-κB, IL-17, and estrogen signaling pathways. Molecular docking revealed favorable
binding affinities of daidzein toward ESR1, CYP19A1, and AKT1, while molecular dynamics simulation
confirmed stable interaction of the CYP19A1–daidzein complex throughout the simulation period. ADMET
prediction indicated favorable intestinal absorption, acceptable drug-likeness, and an overall favorable
pharmacokinetic profile. Overall, these findings of the present study indicate that daidzein may possess
therapeutic potential in PCOS through multi-target modulation of key molecular pathways, thereby
warranting further experimental validation.