Integrated Metabolomics and Proteomics Analysis Reveals the Mechanisms of Banxia-Xiexin Decoction in Colitis-Associated Colorectal Cancer

Colitis-associated colorectal cancer (CAC), a subtype of colorectal cancer arising from chronic colonic inflammation, remains without specific therapeutic agents. Banxia-Xiexin decoction (BXD), a traditional Chinese medicine, is clinically used to treat gastritis and ulcerative colitis; however, its efficacy in CAC and associated mechanisms are not well understood. This study aimed to evaluate the therapeutic potential of BXD against CAC and explore its molecular mechanisms. A CAC mouse model was induced using azoxymethane/dextran sulfate sodium (AOM/DSS), and BXD was administered at vary-ing doses (0.95, 1.9, or 3.8 g/kg/day), alongside a sulfasalazine control. Therapeutic effica-cy was assessed by analyzing disease activity index, inflammatory markers, and histo-pathological changes. Additionally, 4D label-free proteomics and serum metabolomics were conducted to elucidate potential mechanisms. BXD significantly improved disease outcomes in CAC mice by reducing colonic inflammation and tumor hyperplasia, while lowering serum levels of TNF-α, IL-6, IL-1β, and IFN-γ. Metabolomic profiling suggested that BXD modulates valine, leucine, and isoleucine metabolism. Proteomic analysis re-vealed differentially expressed proteins (DEPs) enriched in complement and coagulation cascade pathways. Key DEPs (Fgg, Fgb, C3, and Cfh) were reversed by BXD treatment, which was confirmed at the mRNA level by qRT-PCR. In conclusion, BXD exerts protec-tive effects against CAC by regulating inflammatory responses and modulating amino acid metabolism and complement pathways. These findings provide novel insights into the pharmacological basis of BXD and support its potential clinical application in CAC therapy.