Naringin ameliorates intestinal injury in ulcerative colitis model mice by modulating the JAK2/STAT3 signaling pathway

Ulcerative colitis (UC) is a chronic autoimmune disease characterized by mucosal inflammation and disruption of the intestinal barrier. Current therapies often produce adverse effects, underscoring the need for novel treatment options. Naringin, a flavonoid from Citrus aurantium L., has shown anti-inflammatory potential in inflammatory bowel disease. However, its role in UC via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway remains elusive. The present study investigated the therapeutic effects of naringin on UC, with a focus on JAK2/STAT3 signaling and intestinal barrier restoration. The present study employed a dextran sulfate sodium (DSS)-induced colitis mouse model and IL-6-stimulated Caco-2 cells. Mice were administered 3% DSS for 10 days along with naringin (40 mg/kg) or mesalazine (0.2 g/kg) treatment. Disease activity index (DAI), histopathology, expression of tight junction proteins zona occludens-1 (ZO-1) and occludin and JAK2/STAT3 pathway protein activation were evaluated. In Caco-2 cells, transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran 4 kDa (FD-4) permeability assays assessed barrier function, with STAT3 silencing supporting pathway involvement. Naringin markedly alleviated DSS-induced colitis, reducing weight loss, colon shortening, DAI and histological scores. Furthermore, naringin restored ZO-1 and occludin expression while suppressing JAK2/STAT3 phosphorylation in colon tissues. In Caco-2 cells, naringin reversed IL-6-induced reductions in TEER and increases in FD-4 permeability, while enhancing tight junction fluorescence. Furthermore, STAT3 silencing in combination with naringin led to a further decrease in the p-JAK2/JAK2 ratio compared with that in the IL-6 group (though to a lesser extent than naringin alone), consistent with the involvement of the JAK2/STAT3 pathway. Collectively, these findings demonstrate that naringin ameliorates UC by promoting intestinal barrier repair through suppression of JAK2/STAT3 activation, highlighting its therapeutic potential for UC.