Tannic acid (TA) demonstrates therapeutic potential for gastroenteritis, but its efficacy against ulcerative colitis (UC) remains unclear. This study evaluated the protective effects of TA against dextran sulfate sodium (DSS)-induced murine colitis. Mice were administered TA (20, 40, or 80 mg/kg) or sulfasalazine (SASP). TA treatment significantly ameliorated colitis severity, as demonstrated by improved body weight recovery, reduced disease activity index (DAI), and attenuated colon shortening. Mechanistically, TA suppressed oxidative stress and inhibited the NF-κB signaling pathway, thereby reducing inflammatory responses. Additionally, TA enhanced intestinal barrier function through increased expression of key tight junction proteins. Furthermore, TA administration dose-dependently remodeled the gut microbiota, with low and medium doses (20 and 40 mg/kg) exhibiting efficacy comparable or superior to SASP. These findings indicate that TA ameliorates DSS-induced colitis through synergistic antioxidant, anti-inflammatory, and microbiota–modulatory actions, highlighting its potential as a natural therapeutic or adjunctive agent for UC.
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