Objective To investigate the therapeutic effect of schisandrin B (Sch B) on ulcerative colitis (UC) in rats induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS), and explore its molecular mechanism in alleviating pyroptosis of colonic epithelial cells by regulating autophagy-related proteins as well as NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/cysteine-aspartic protease-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway. Methods SD rats were randomly divided into control group, model group, mesalazine (100 mg/kg) group, Sch B low-, medium- and high-dose (10, 20, 50 mg/kg) groups, with 10 rats in each group, half male and half female. A TNBS-induced UC model was constructed, after 14 consecutive days of administration, the general conditions of rats were observed. The disease activity index (DAI) score, colon length and colon mucosa damage index (CMDI) score were detected. Histopathological injury of colonic tissue was evaluated by hematoxylin-eosin (HE) staining. Levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in serum were measured by ELISA. The expressions of autophagy related protein 16 like protein 1 (ATG16L1) and GSDMD proteins in colonic tissue were detected by immunohistochemistry. Western blotting was performed to detect the expressions of autophagy-related proteins (Beclin-1, microtubule-associated protein light chain 3B (LC3B), ATG16L1, p62) and pyroptosis pathway-related proteins (NLRP3, Caspase-1, GSDMD) in colonic tissue. Results Compared with model group, Sch B significantly ameliorated body weight loss, hematochezia and other symptoms in UC rats, reduced DAI and CMDI scores (P < 0.05, 0.01), increased colon length (P < 0.05, 0.01), alleviated colonic mucosal congestion, edema, ulcer formation and inflammatory cell infiltration (P < 0.05, 0.01), decreased levels of IL-6, TNF-α and IL-1β in serum (P < 0.05, 0.01), upregulated Beclin-1 protein expression and LC3-Ⅱ/Ⅰ ratio in colonic tissue (P < 0.01), and downregulated ATG16L1, p62, NLRP3, Caspase-1, GSDMD protein expressions (P < 0.05, 0.01). Conclusion Sch B exerts a remarkable therapeutic effect on TNBS-induced UC in rats. Its mechanism may be associated with maintaining autophagy flux homeostasis, inhibiting colonic epithelial cell pyroptosis mediated by NLRP3/Caspase-1/GSDMD signaling pathway, reducing the release of pro-inflammatory factors and thereby alleviating intestinal inflammatory response. Normalization of autophagy flux may be a key regulatory link for Sch B to inhibit colonic epithelial cell pyroptosis.

schisandrin B  /  ulcerative colitis  /  pyroptosis  /  autophagy  /  inflammatory response  /  NLRP3/Caspase-1/GSDMD signaling pathway