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This study was carried out to investigate the potential therapeutic effect of galangin, a promising active principle of honeybee propolis, in dextran sulphate sodium (DSS)–induced colitis in mice. We explored the possible underlying mechanisms for galangin action and the therapeutic benefit of adding galangin to the standard therapy sulphasalazine. A galangin dose of 40 mg/kg was selected based on a preliminary dose‐selection study for investigation in a 4‐week cyclical model of DSS‐induced colitis. Mice received 3% DSS in their drinking water during the first and third weeks and were administered the treatments (40 mg/kg galangin, 100 mg/kg sulphasalazine and a combination of 20 mg/kg galangin and 50 mg/kg sulphasalazine) daily starting from the second week. Galangin significantly ameliorated DSS‐induced histopathological alterations and tissue injury, down‐regulated Toll‐like receptor 4 expression, suppressed NF‐κB p65 activation, lowered inflammatory cytokine levels and demonstrated antioxidant effects. The combination of galangin and sulphasalazine at half doses yielded comparable results to either drug alone at full dose. This study highlights galangin as a promising therapy for colitis management.

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