Ganggang Miao, D. C. Zhang, Zhenghui Sui, Jianfei Leng, Yanxiang Deng, Xingwei Gu, Hongyong Cao
Inflammatory bowel disease (IBD) is pathologically characterized by dysregulated inflammation and compromised intestinal barrier integrity. While multi-component herbal formulations hold promise for IBD management, the combined potential of specific phytochemical combinations remains underexplored. This study investigates the cooperative therapeutic effects of Berberine and Taxifolin, two anti-inflammatory phytochemicals, in a murine colitis model. Multi-omics network pharmacology initially identified their shared anti-inflammatory and anti-apoptotic targets in IBD pathogenesis. Experimental validation demonstrated that combined treatment with berberine and taxifolin produced stronger protective effects against Dextran Sulfate Sodium (DSS)-induced colitis than either compound alone. Specifically, the combination significantly alleviated body weight loss and colon shortening, reduced macrophage infiltration and the expression of pro-inflammatory cytokines (IL-1β and TNF-α), and preserved intestinal barrier integrity by restoring tight junction proteins (occludin and ZO-1). In addition, the combined treatment attenuated caspase-3-mediated epithelial apoptosis. Molecular docking analysis suggested that berberine and taxifolin may interact with multiple inflammation-related targets, including NF-κB, NLRP3, PPARγ, and STAT3, providing a potential mechanistic basis for the observed effects. These findings establish Berberine-Taxifolin co-administration as a novel multi-target therapeutic strategy that concurrently addresses inflammatory dysregulation, barrier repair, and apoptosis control in IBD, and may provide a phytochemical blueprint for complex inflammatory disorders.