Mechanisms of Qu's Formula 3 for Improving Endometrial Receptivity in PCOS: A Combination of Network Pharmacology and Molecular Dynamics Simulation.

Impaired endometrial receptivity is a major cause of infertility in polycystic ovary syndrome (PCOS). Qu's Formula 3 (QUF3) is a Chinese herbal medicine formula clinically used to improve endometrial receptivity in patients with PCOS. This study employed network pharmacology, molecular docking, and molecular dynamics (MD) simulations to investigate the underlying mechanisms. Active constituents of QUF3 were identified using the TCMSP database, and potential targets related to endometrial receptivity and PCOS were retrieved from DrugBank and other resources. A compound-target interaction network and a protein-protein interaction (PPI) network were constructed via Cytoscape to identify key targets. Core targets were subjected to GO and KEGG enrichment analyses. Molecular docking, MD simulations, principal component analysis (PCA), free energy landscape (FEL), and dynamic cross-correlation matrix (DCCM) were used to evaluate binding interactions. From 91 active ingredients and 294 potential drug targets, 60 disease-related targets were identified. Luteolin and sesamin were among the key pharmacodynamic components. Ten core targets were identified: AKT1, EGFR, TNF, TP53, IL6, BCL2, ESR1, IL1B, STAT3, and MMP9. KEGG enrichment revealed 132 signaling pathways, and GO analysis identified 678 entries. MD simulations indicated that the binding between the top five active constituents and their respective targets was stable. PCA, FEL, and DCCM further demonstrated high thermodynamic stability and structural rigidity of these complexes. In conclusion, QUF3 improves endometrial receptivity in PCOS through multicomponent, multitarget, and multipathway interactions. This study provides a theoretical basis, from a computational simulation perspective, for the development of targeted Chinese herbal medicine therapies for PCOS-related infertility, and may have positive implications for improving pregnancy outcomes in women with PCOS in the future.