IDDF2026-ABS-0368 Codonopsis pilosula oral liquid attenuates chronic DSS-induced colitis and reveals potential microbial and target-predicted mechanisms

Background Ulcerative colitis (UC) is characterized by impaired mucosal barrier function, excessive inflammation, and oxidative stress. Codonopsis pilosula Nnannf. (CPN) has shown therapeutic potential in UC. Its water-extract–ethanol-precipitated oral formulation (CPNL) may exert similar or stronger effects, yet its mechanism remains unclear. To evaluate the therapeutic efficacy of CPNL in DSS-induced chronic colitis and clarify its pharmacological and microecological mechanisms. Methods A total of 48 C57BL/6 mice were used in this study, with 8 mice per group. Chronic colitis was induced in mice using 2% DSS (IDDF2026-ABS-0368 Figure 1. CPN and CNPL treatment ameliorates experimental colitis in mice). Disease severity was assessed by body weight, disease activity index (DAI), colon length, histopathology, cytokine levels, and expression of barrier-related proteins. Gut microbiota composition was analyzed by 16S rRNA sequencing. Active constituents of CPNL were identified by UPLC-Triple-TOF/MS. Network pharmacology was applied to predict potential pathways, followed by molecular docking to validate interactions with HIF-1α and oxidative stress–related targets. Results CPNL significantly alleviated DSS-induced colitis (P<0.01), normalized inflammatory cytokinesTNF-α, IL-6, IL-17, IL-10 (P<0.05), and enhanced colonic epithelial barrier function via upregulating MUC-2, ZO-1, Occludin, Claudin-1. CPNL targets were enriched in HIF-1, TNF, and ROS pathways (P<0.01), with major components binding HlF-1α (binding energy < -5kcal/mol). CPNL reshaped the gut microbiota and increased Akkermansia abundance (P<0.05) (IDDF2026-ABS-0368 Figure 2. CPNL alleviates DSS-induced colitis via targeting HIF and restoring gut microbiota). Conclusions CPNL mitigates chronic colitis by modulating inflammation, reinforcing barrier function, regulating oxidative stress, and remodeling the gut microbiota. The enrichment of Akkermansia may serve as a key microbial mediator linking CPNL to HIF-1/oxidative stress modulation. These findings provide a new microecological perspective on the multi-component, multi-target mechanisms of traditional herbal medicines.