Potential Molecular Mechanism of Guishen Huoxue Decoction against Intrauterine Adhesion Based on Network Pharmacology

Abstract

Objective. Intrauterine adhesion (IUA) represents an endometrial repair disorder that is associated with menstrual disorders, recurrent pregnancy loss, and infertility. This study aimed to explore the underlying biological mechanisms of Guishen Huoxue decoction for the treatment of IUA based on network pharmacology. Methods. The selection of active compounds for Guishen Huoxue decoction and prediction of relevant targets were performed by the TCMSP and Swiss Target Prediction databases, respectively. The targets of IUA were obtained by three databases, including Online Mendelian Inheritance in Man (OMIM), DisGeNET, and GeneCards. The drug-disease regulatory network was constructed via Cytoscape software, following the acquisition of common genes of active compounds of drug Guishen Huoxue decoction and disease IUA, which was carried out through Venny software. Protein-protein interaction (PPI) network and function enrichment analyses were performed. Results. According to the data obtained from TCMSP, a total of 200 potential active compounds of Guishen Huoxue decoction and their related targets (1068) were screened by the Swiss Target Prediction database. 1303 disease targets and 134 common targets were identified. The drug-disease regulatory network showed that 165 active compounds were found to be involved in the treatment of IUA. Among 134 common targets, AKT1, SRC, TP53, VEGFA, and IL-6 were predicted as core genes against IUA. PI3K-Akt, Rap1, Ras, and AGE-RAGE were the main signaling pathways that participated in the treatment of Guishen Huoxue decoction for IUA. Conclusion. The active compounds of Guishen Huoxue decoction confer therapeutic effects against IUA by regulating fibrosis, inflammation, and oxidative stress through major signaling pathways such as PI3K-Akt and AGE-RAGE.