Betaine Ameliorates Acute Sever Ulcerative Colitis by Inhibiting Oxidative Stress Induced Inflammatory Pyroptosis

Scope Betaine rich in beet is used as an important source of human nutrition. Here this study aims to explore whether betaine supplementation can protect against acute sever ulcerative colitis (ASUC) and the underlying mechanism Methods and results ASUC model is induced by dextran sulfate sodium (DSS), and effects of betaine as a methyl donor on ASUC are evaluated. Betaine mitigates the changes, for example, elevated DAI, weight loss, spleen enlargement, colon shortening, and disordered colonic mucosa. The protective effects of betaine on colonic barrier integrity in ASUC are then verified through examining tight junction proteins by western blot and immunofluorescence. Spectrophotometry method and western blot confirm that betaine can decrease levels of oxidative markers (MDA, MPO, NOS, and COX2), and promote expressions of antioxidant proteins (GSH, NRF2, CAT, and SOD1). Further, betaine prevents colonic inflammatory pyroptosis by blocking expressions of NLRP3 inflammasome complex (NLRP3, ASC, and cleaved‐caspase 1), N terminal‐GSDMD, and release of relevant inflammatory factors. Conclusion Betaine inhibits colonic oxidative stress induced inflammatory pyroptosis to alleviate ASUC, which shows therapeutic potential against colitis and other acute inflammatory disorder.