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

• • Sch B (10, 20, 50 mg/kg) significantly reduced DAI and CMDI scores (P<0.05, 0.01) and increased colon length (P<0.05, 0.01) in TNBS-induced UC rats, demonstrating dose-dependent mucosal protection and clinical potential for reducing disease severity. • • Sch B upregulated Beclin-1 and elevated LC3-II/I ratio (P<0.01) while downregulating ATG16L1 and p62 (P<0.05, 0.01), indicating restoration of autophagic flux from initiation to degradation, a critical mechanism for clearing damaged organelles and mitigating epithelial injury. • • Sch B downregulated NLRP3, Caspase-1, and GSDMD protein expression (P<0.05, 0.01), directly inhibiting the pyroptosis pathway and reducing serum IL-6, TNF-α, and IL-1β levels (P<0.05, 0.01), thereby breaking the pyroptosis-inflammation cycle. • • The study establishes a causal link between autophagic flux normalization and pyroptosis suppression, with Sch B's multi-target effects offering a therapeutic advantage over single-target anti-inflammatory agents, though cell-level validation and autophagy blockade rescue experiments are needed to confirm causality.