Predicting the Mechanism of Indirubin in the Treatment of Chronic Ulcerative Colitis Based on Public Database Analysis

Objective: To identify the key genes and potential signaling pathways of indirubin against Ulcerative colitis (UC). Methods: Two mRNA datasets (GSE37283 and GSE87466) were obtained from the Gene Expression Omnibus (GEO) database. Mucosal biopsy samples isolated from patients with UC and healthy normal subjects were analyzed to identify differentially expressed genes (DEGs), and a protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes (STRING) database. The module analysis of the PPI network and hub genes identification were performed using Cytoscape software3.7.2. Key gene analysis of DEGs was performed using the MCODE plugin in Cystoscope as well as the Hubba plugin. Functional and pathway enrichment analyses were performed via the ClueGo plugin in Cytoscape and validated using Gene Set Enrichment Analysis. The therapeutic targets were then analyzed by pharmacophore network pharmacology, intersected to identify the therapeutic targets of indirubin and the related signaling pathways. The 3D structures of the therapeutic target proteins were predicted by the artificial intelligence AlphaFold2 and molecular docking was used to verify whether indirubin could be successfully docked to the predicted targets or not. Results: 245 DEGs were acquired, and 13 hub genes for UC were screened by the MCODE and Hubba plug-in. 126 target genes were acquired through pharmacophore target analysis, and 4 therapeutic targets were obtained. 6 therapeutic signaling pathways were identified. Conclusions: Indirubin can relieve UC by the four therapeutic target genes, including MMP9, PTGS2, PDE4B, and PTPRC, as well as IL-17 and TNF signaling pathway.