Network Pharmacology of Xian-Lian-Jie-Du Decoction in Ameliorating Colorectal Cancer

Abstract Objective: In this study, we screened for therapeutic targets of the Xian-Lian-Jie-Du decoction (XLJDD) for colorectal cancer (CRC) and explored the underlying mechanisms using network pharmacology techniques. Methods: Genes associated with CRC were collected from the GeneCards database. The names of the active compounds of XLJDD were used as keywords in the “chemical name” in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database to search the targets. The protein–protein interaction (PPI) network was constructed using Cytoscape 3.8.1. Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to identify key target proteins. Results: A total of 234 XLJDD-related targets and 250 cross-targets between XLJDD and CRC were collected based on the TCMSP and HIT 2.0 databases. A PPI network constructed based on the STRING database revealed interactions for all 250 proteins. The network results revealed TP53, MYC, CCND1, AKT1, CASP3, and STAT3 as core potential targets. KEGG pathway analysis of the 250 potential XLJDD targets for CRC in the Metascape database was performed using RStudio software. The top 12 gene ratio aggregated analysis results were visualized in bubble charts. The interleukin (IL)-17 signaling pathway had the highest correlation with the tumor necrosis factor (TNF) signaling pathway. Conclusions: XLJDD may be effective in ameliorating CRC by controlling inflammatory factors related to the IL-17 and TNF pathways and targeting proto-oncogenes and tumor suppressor genes, including MYC, CCND1, CTNNB1 , and TP53 .