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

Abstract

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 fromL., 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.