Exploring the Anticancer Effects of Xianliu Jieduan Fang on Colitis-Associated Colorectal Cancer Through Network Pharmacology and Experimental Validation

Abstract

This study evaluated the therapeutic effects of Xianliu Jieduan Fang (XLJDF) on colitis-associated colorectal cancer (CAC) and explored its molecular mechanisms through network pharmacology and experimental validation. Using an AOM/DSS-induced CAC mouse model, we evaluated XLJDF's efficacy. Active components were identified by UHPLC-QE-HRMS. Targets were predicted using SwissTargetPrediction and PubChem, while disease genes were obtained from GeneCards, DisGeNET, and TTD. Core targets and pathways were analyzed via Cytoscape and Metascape. Mechanisms were validated through molecular docking and experiments. XLJDF improved colon pathology and identified 68 active compounds, including nine key components like Kaempferol and Luteolin. Network analysis revealed 959 targets with 29 core genes (AKT1, CTNNB1, GSK3B, etc.). KEGG analysis showed XLJDF primarily acts through Wnt signaling, regulating apoptosis and cell migration. Experimental validation confirmed XLJDF inhibits Wnt/β-catenin pathway by preventing GSK3β inactivation. XLJDF exerts anti-CAC effects via a multi-component, multi-target network. Our study identifies key active compounds and demonstrates that XLJDF suppresses the Wnt/β-catenin pathway by preventing GSK3β inactivation, thereby inhibiting β-catenin stabilization.