Mechanism of Schisandrin B in Alleviating Pyroptosis of Epithelial Cells in Rats with Ulcerative Colitis Based on Regulation of NLRP3/Caspase-1/GSDMD Signaling Pathway by Autophagy
Ulcerative colitis (UC) remains a clinical challenge due to inadequate mucosal healing and high relapse rates. This study investigates the therapeutic efficacy of schisandrin B (Sch B) in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced rat model of UC, focusing on the interplay between autophagy and pyroptosis. SD rats were randomized into control, model, mesalazine (100 mg/kg), and Sch B low-, medium-, and high-dose (10, 20, 50 mg/kg) groups (n=10 per group). After 14 days of treatment, disease activity index (DAI), colon length, and colon mucosa damage index (CMDI) were assessed. Histopathology, serum cytokine levels (TNF-α, IL-6, IL-1β), and protein expression of autophagy markers (Beclin-1, LC3B, ATG16L1, p62) and pyroptosis pathway components (NLRP3, Caspase-1, GSDMD) were evaluated. Sch B significantly ameliorated weight loss, hematochezia, and colon shortening (P<0.05, 0.01), reduced DAI and CMDI scores, and attenuated mucosal edema, ulceration, and inflammatory infiltration. Serum IL-6, TNF-α, and IL-1β levels were markedly decreased (P<0.05, 0.01). Sch B upregulated Beclin-1 and increased LC3-II/I ratio (P<0.01), while downregulating ATG16L1, p62, NLRP3, Caspase-1, and GSDMD (P<0.05, 0.01). These findings indicate that Sch B restores autophagic flux homeostasis, thereby suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis and reducing pro-inflammatory cytokine release. The normalization of autophagic flux is a critical upstream mechanism for Sch B's inhibition of colonic epithelial pyroptosis, offering a multi-target therapeutic strategy for UC.