Bioactive Compounds and Mechanistic Insights of Chuanxiong Rhizoma and Angelicae Sinensis Radix in Endometriosis Treatment: A Network Pharmacology and Experimental Validation Study

INTRODUCTION: Endometriosis, a chronic gynecological disorder, significantly impacts fertility and quality of life. Identifying effective therapeutic targets is critical for their management. OBJECTIVES: The objective of this study was to explore the therapeutic potential of Chuanxiong Rhizoma and Angelicae Sinensis Radix (CXDG) in treating endometriosis by identifying active compounds and key molecular targets, with a particular emphasis on ESR1 as a potential regulatory hub involved in disease progression. METHODS: A bioinformatics approach identified active compounds from CXDG and their therapeutic targets. WGCNA identified key gene modules related to endometriosis, while machine learning models identified critical genes associated with the disease. Molecular docking and assays (CCK-8, EdU, Transwell) evaluated compound effects on cell proliferation, invasion, and migration. RESULT: Machine learning models identified ESR1, HMGCR, and NTRK2 as key molecular targets. Molecular docking showed Coniferyl Ferulate binds ESR1. Coniferyl Ferulate inhibited the proliferation, invasion, and migration of endometriosis cells. Immune infiltration analysis revealed differences in immune cell composition linked to ESR1 expression. DISCUSSION: Our findings suggest that ESR1 modulates immune responses in endometriosis, with Coniferyl Ferulate showing potential to inhibit cell proliferation and migration. Future studies, including animal models and clinical trials, are necessary to confirm its efficacy and explore combination therapies for enhanced treatment outcomes. CONCLUSION: Coniferyl Ferulate exhibits therapeutic potential against endometriosis by inhibiting cell proliferation, migration, and invasion. ESR1 acts as a central regulatory hub linking hormonal and immune pathways, suggesting that CXDG may exert multi-target effects by modulating ESR1-mediated signaling.