Mechanism of Curcumin in the Treatment of Intrauterine Adhesions Based on Network Pharmacology, Molecular docking, and Experimental Validation

Intrauterine adhesions (IUA) is one of the most prevalent gynecological conditions affecting women of childbearing age. The active ingredient curcumin (CUR), derived from turmeric, is a promising candidate for the treatment of IUA. Nevertheless, the mechanism of action remains undetermined. This study investigates the role and mechanism of CUR in the treatment of IUA through network pharmacology, molecular docking, and Molecular Biology experiments. IUA-related targets were sourced from the GeneCards database. CUR-related targets were obtained from Herb and SwissTarget Prediction. Cytoscape version 3.10.2 was employed to construct PPI networks and to identify core targets. GO and KEGG enrichment analyses were conducted using the DAVID database. Additionally, molecular docking was employed to evaluate the interaction between CUR and core targets. Finally, the mechanism and targets of CUR in IUA were validated through animal experiments. A total of 122 common target points for CUR and IUA were identified. Topological analysis and KEGG analysis identified 20 core target points, encompassing multiple pathways, including inflammation and the PI3K/Akt signaling pathway. Molecular docking results demonstrated that CUR exhibits a strong binding affinity for the core target points. In vivo experiments indicate that CUR significantly alleviates the fibrosis and epithelial-mesenchymal transition (EMT) processes of the endometrium in IUA rats while inhibiting the overexpression of TGF-β1 in the uterine tissue of IUA rats and the activation of the PI3K/Akt and TLR4/NLRP3 signaling pathways. CUR can inhibit fibrosis and the EMT process in the endometrium of IUA rats, and its mechanism may be associated with the inhibition of the PI3K/Akt and TLR4/NLRP3 signaling pathways.

Curcumin; Intrauterine adhesions; Molecular docking; Network pharmacology; Phosphatidylinositol 3-kinase/protein kinase B; Toll-like receptor 4/NOD-like receptor thermal protein domain associated protein 3.