Spinosin attenuates DSS-induced ulcerative colitis in rats in association with increased Nrf2/HO-1 and reduced TLR4/NFKB1-related inflammatory markers.

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 oral 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. Spinosin reduced IL-6, TNF-α, TGF-β, PGE₂, Bax, NFKB1 p105/p50 protein levels, and TLR4 mRNA expression, with the most consistent effects observed at 10 and 20 mg/kg. 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.