Kui‐Jie‐Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota

Abstract Background and Aim Kui‐Jie‐Ling capsule (Kui‐Jie‐Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui‐Jie‐Ling and Kui‐Jie‐Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS). Methods Network pharmacology was combined with an animal experiment to reveal the targets of Kui‐Jie‐Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7 days. On the second day, the mice in the Kui‐Jie‐Ling group were orally administered with Kui‐Jie‐Ling (1.5 and 3.0 g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui‐Jie‐Ling (3.0 g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short‐chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments. Results The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui‐Jie‐Ling alleviated UC via multi‐pathway. Kui‐Jie‐Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide–toll‐like receptor 4/nuclear factor kappa B and interleukin‐23–Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis. Conclusion These studies provided the experimental basis for the clinical administration of Kui‐Jie‐Ling and Kui‐Jie‐Ling combined with adalimumab against UC.