Integrated Strategy Combining Real-World Data Mining, Network Pharmacology, and Molecular Docking to Decipher the Mechanism of Action of a Core Herbal Combination for Menopausal Syndrome

Abstract

Background Menopausal syndrome (MPS) affects most peri- and post-menopausal women, and the multi-target nature of traditional herbal therapy makes its mechanism of action difficult to characterize with conventional methods. Objective This study aims to elucidate the treatment strategy and molecular basis of Professor Zhang Xiaodan’s herbal therapy for menopausal syndrome (MPS) through an integrated approach combining clinical data mining, network pharmacology, and molecular docking. Methods A total of 158 clinical prescriptions (January 2024–January 2025) were analyzed. Core herbal combinations were identified via association rule mining and hierarchical clustering and subsequently validated through expert review. Bioactive compounds were retrieved from TCMSP, while disease-related targets were sourced from GeneCards, OMIM, DrugBank, and TTD. Protein–protein interaction (PPI) networks were constructed and analyzed, and functional enrichment was performed using R. Molecular docking simulations validating key interactions. Results Analysis of 142 herbs (2,212 applications) revealed Licorice, Scutellaria, and Glehnia as the most frequent. Herbs were primarily cold-natured, sweet-bitter, and targeted lung/liver/kidney meridians. Data mining revealed 48 high-frequency herb pairs and three major clusters, from which an 8-herb core formula was derived. Network analysis identified 252 active compounds, 195 overlapping targets, and 10 core targets, including MAPK1, ESR1, and TP53. Enrichment analysis highlighted pathways related to lipid metabolism, AGE-RAGE signaling, and PI3K–AKT signaling. Molecular docking demonstrated strong binding affinities, notably between luteolin and MAPK1. Conclusion Professor Zhang’s treatment strategy emphasizes nourishing yin and blood, clearing heat, and regulating qi. The core formula likely exerts therapeutic effects via multi-target mechanisms involving ESR1 and TP53 through key signaling pathways, offering a mechanistic explanation for its clinical efficacy against MPS.