Network Pharmacology, Molecular Docking, and Experimental Validation Revealthe Mechanism of Qingfudaotan Formula in PCOS Treatment

Introduction: Qingfudaotan Formula (QFDT) is a classical traditional Chinese medicine (TCM) compound used for polycystic ovary syndrome (PCOS), yet its underlying mechanisms remain unclear. This study aimed to elucidate the pharmacological mechanism of QFDT in alleviating PCOS. Methods: Active ingredients and targets of QFDT, along with PCOS-associated genes, were retrieved from public databases. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed. Core targets and active ingredients were further validated via molecular docking. A PCOS rat model was utilized for experimental verification. Results: QFDT identified 62 potential PCOS targets, with PPI analysis pinpointing 12 core targets (e.g., AKT1, NFKB1). GO/KEGG enrichment implicated insulin resistance and NF-κB pathways. Molecular docking predicted strong binding (≤-5 kcal/mol) for 5 active ingredients to 5 key targets. In PCOS rats, QFDT significantly reduced body weight and cystic follicles and restored estrous cycles. It notably lowered HOMA-IR (QFDT-H, P<0.05), upregulated ovarian P-PI3K/PI3K and P-AKT/AKT ratios (QFDT-H, P<0.05), and downregulated TLR4/MyD88/p-NFκB, alongside inflammatory markers (LPS, IL-6, TNF-α, etc., QFDT-H, P<0.05). Discussion: Chronic low-grade inflammation and insulin resistance play critically important roles in the pathogenesis of PCOS. This study demonstrates that QFDT, as a traditional Chinese herbal formula, alleviates PCOS by ameliorating insulin resistance via the PI3K/AKT pathway and suppressing inflammation through the TLR4/NF-κB pathway. Conclusion: This study identified targets for QFDT in PCOS treatment, helping elucidate the mechanisms of action of this ingredient and its potential clinical applications.