Network pharmacology prediction of UA in targeting endometriosis progression to endometrial cancer

UNLABELLED: Endometriosis is a gynecological disorder predominantly affecting women of reproductive age and is considered a potential risk factor for the development of endometrial cancer. However, the molecular mechanisms underlying the transition from EMS to EMC remain unclear. In this study, Ursolic acid (UA), a natural compound identified in the hydroalcoholic extract of Putranjiva roxburghii leaves, was investigated for its therapeutic potential in modulating this progression. A network pharmacology-based approach was employed to predict UA target genes using databases such as Swiss Target Prediction, TargetNet, and GeneCards. Among 132 identified targets, ten core genes-TNF, IL6, AKT1, EGFR, MMP9, SRC, BCL2, ESR1, MAPK3, and ERBB2 were prioritized based on their interaction degree. Subsequent analyses, including gene ontology, KEGG pathway mapping, mRNA expression, immunohistochemistry, and molecular docking, revealed key signaling pathways and gene interactions relevant to progression of EMC from EMS. Experimental validation was conducted through real-time PCR, MTT assay, and AO/PI staining on human primary endometrial cells. Collectively, our findings integrate computational and experimental evidence, highlighting UA as a promising candidate for mitigating the progression of endometriosis to endometrial cancer and offering new insights into its molecular mechanism. GRAPHICAL ABSTRACT: Schematic presentation of impact of ursolic acid in targeting endometriosis progression to endometrial cancer: a comprehensive network pharmacology study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00492-5.