Spinosin Attenuates DSS-Induced Ulcerative Colitis in Rats in Association with Increased Nrf2/HO-1 and Reduced TLR4/NFKB1-Related Inflammatory Markers.

PMID 42431338 | DOI 10.1016/j.ejphar.2026.179117 · European journal of pharmacology · 2026

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BACKGROUND: Ulcerative colitis involves epithelial injury, oxidative stress, and exaggerated inflammatory signaling. This study evaluated the protective effects of spinosin in dextran sulfate sodium (DSS)-induced colitis in rats. METHODS: Colitis was induced using 2% DSS in drinking water. Rats received intraperitoneal spinosin (5, 10, or 20 mg/kg) or sulfasalazine once daily. Clinical indices, macroscopic injury, oxidative/nitrosative stress, inflammatory mediators, Nrf2/HO-1-related markers, TLR4/NFKB1-associated markers, apoptosis-related proteins, MCP-1, and tight junction gene expression were assessed. RESULTS: DSS caused body-weight loss, colon shortening, splenomegaly, increased disease activity index (DAI), oxidative/nitrosative stress, inflammatory mediator upregulation, and reduced tight junction gene expression. Spinosin improved day-8 body weight at 10 mg/kg (p<0.05) and 20 mg/kg (p<0.001), restored colon length at 10 and 20 mg/kg (p<0.001), reduced spleen index at 20 mg/kg (p<0.001), and decreased DAI at all doses (p<0.001). Spinosin reduced LDH at 5 mg/kg (p<0.05) and 10-20 mg/kg (p<0.001), and reduced MPO, MDA, NO, COX-2, iNOS, and MCP-1 (p<0.001). It lowered IL-6, TNF-α, TGF-β, PGE2, Bax, TLR4/NFKB1-associated inflammation, with dose-dependent significance at p<0.05, p<0.01, or p<0.001. Spinosin also increased antioxidant defenses, HO-1, Nrf2, IL-10, Bcl-2, and ZO-1/occludin mRNA expression, mainly at 10-20 mg/kg (p<0.001). CONCLUSIONS: Spinosin attenuates DSS-induced colitis in rats, with effects associated with improved redox balance, increased Nrf2/HO-1-related cytoprotective markers, reduced inflammatory mediators, and restored barrier-associated gene expression.