Ebastine attenuates DSS-induced ulcerative colitis via modulation of NF-κB, oxidative stress and pro-inflammatory cytokines: evidence for antihistamine repurposing.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, driven by immune dysregulation, oxidative stress, and the release of pro-inflammatory cytokines. Histamine, an important mediator in gut inflammation, has immunomodulatory properties. Ebastine, a second-generation histamine H1-receptor antagonist, is primarily used for allergic conditions, but its potential role in managing IBD has not been fully explored. This study aimed to evaluate whether ebastine could prevent colitis induced by dextran sodium sulfate (DSS) in mice. The severity of the condition was assessed using the disease activity index (DAI), body weight loss, stool consistency, and rectal hemorrhage. Immune modulation was investigated by measuring serum IgE levels and inflammatory biomarkers like C-reactive protein (CRP). The study also examined the impact of ebastine on oxidative stress markers and pro-inflammatory cytokines (TNF-α, IL-6), alongside histopathological analysis of colon tissue. Swiss albino mice were induced with experimental colitis using 3% DSS and divided into five groups, including a normal control, DSS control, standard treatment (sulfasalazine), and two ebastine-treated groups (2 mg/kg and 10 mg/kg). Clinical, histopathological, and molecular markers were analyzed. Ebastine significantly improved clinical parameters, reduced DAI, inhibited oxidative stress, and lowered TNF-α and IL-6 levels. The high dose showed more potent anti-inflammatory effects, while the low dose demonstrated better antioxidant activity. Ebastine offers protection against DSS-induced colitis by modulating inflammation and oxidative stress, suggesting its potential as an adjunctive treatment for IBD.