OBJECTIVE To explore the potential mechanisms of Xie-Ke Decoction, based on the "Ke-Nang theory", in treating polycystic ovary syndrome (PCOS) and to identify its potential therapeutic targets, thereby providing a theoretical basis for the application of the "Ke-Nang theory" in PCOS treatment.

METHODS The components of Xie-Ke Decoction and its potential targets for PCOS treatment were retrieved from databases such as TCMSP, SwissTargetPrediction, GeneCards, CTD, and GEO. A component-target network was constructed using Cytoscape, and GO and KEGG enrichment analyses were performed to elucidate its mechanisms of action. LASSO and Wilcoxon tests were used to screen and validate key targets, and molecular docking was conducted to verify the binding affinity between core components and key targets. Clinical samples were collected, and ELISA was used to validate the predicted targets.

RESULTS A total of 29 core genes were identified, with GO enrichment analysis involving pathways such as inflammatory response, metabolic regulation, and extracellular matrix remodeling. KEGG enrichment analysis covered pathways like cancer pathways, inflammatory pathways, insulin resistance, and lipid metabolism pathways. Five effective targets were ultimately screened and validated: CTSL, FABP5, HMOX1, PIK3CD, and MMP9. The core component quercetin showed strong affinity for MMP9. Clinical studies revealed that the number of retrieved oocytes and the levels of MMP-9 in follicular fluid were significantly higher in the Xie-Ke Decoction treatment group than in the control group (P < 0.05).

CONCLUSION The therapeutic targets and pathways of Xie-Ke Decoction in treating PCOS are revealed by network pharmacology and verified by molecular docking and clinical research, providing scientific evidence for its mechanism of action. It also lays a theoretical foundation for the clinical application and pharmacological research of the "Ke-Nang theory".