Banxia-Xiexin Decoction Ameliorates Colitis-Associated Colorectal Cancer by Modulating Inflammatory Responses and the Complement and Coagulation Cascade Pathway

Qiang Chen, Maoxu Wang, Wei Shi, Yinan Liu, Liying Wang, Yuegang Zhao, Zhidong Qiu, Ye Qiu, Xuelian Dong Institute of College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of ChinaCorrespondence: Xuelian Dong, Email [email protected]: Colitis-associated colorectal cancer (CAC), a subtype of colorectal cancer arising from chronic colonic inflammation, currently lacks specific therapeutic agents. Banxia-Xiexin decoction (BXD), a traditional Chinese medicine, is clinically used for gastritis and ulcerative colitis; however, its efficacy and underlying mechanisms in CAC remain unclear. This study aimed to evaluate the therapeutic potential of BXD against CAC and elucidate its molecular mechanisms.Methods: A CAC mouse model was induced using azoxymethane/dextran sulfate sodium (AOM/DSS). Mice received BXD at low, medium, and high doses (0.95, 1.9, or 3.8 g/kg/day) by oral gavage from day 21 to day 70, or sulfasalazine (0.6 g/kg/day) as a positive control. Therapeutic efficacy was evaluated by disease index (DI), histopathology, and inflammatory cytokine levels (TNF-α, IL-6, IL-1β, IFN-γ). Metabolomic profiling and proteomic analysis were performed to identify altered metabolic pathways and differentially expressed proteins (DEPs). Key pathway-related genes were validated by qRT-PCR.Results: BXD treatment significantly alleviated clinical symptoms, attenuated colonic inflammation, and reduced both tumor number and size compared with the model group. Inflammatory cytokines were markedly decreased. Metabolomics revealed modulation of amino acid and glycerophospholipid metabolism, while proteomics identified DEPs enriched in the complement and coagulation cascades. Expression of key proteins (C3,Fgg, Cpb2, Cfh) and corresponding mRNAs was reversed by BXD.Conclusion: BXD may ameliorate CAC by modulating inflammatory responses and glycerophospholipid metabolism, with particular involvement of the complement and coagulation cascades. These findings provide mechanistic insight into the potential anti-CAC effects of BXD and support its further investigation for clinical application.Keywords: Banxia-Xiexin decoction, colitis-associated colorectal cancer, serum metabolomics, proteomics, complement and coagulation cascades