P101 Isosteviol Attenuates Dextran Sulfate Sodium-Induced Colitis by Maintaining the Intestinal Barrier Through PDK1/AKT/NF-κB Signaling

Yao, L.(1);Cao, Q.(1);

(1)Sir Run Run Shaw Hospital- College of Medicine Zhejiang University, Department of Gastroenterology, Hangzhou, China;


Inflammatory bowel disease (IBD) is a chronic debilitating inflammatory disorder of the gastrointestinal tract that is characterized by intestinal epithelial barrier dysfunction and excessive activation of the mucosal immune system. Isosteviol (IS) has been reported to possess anti-inflammatory properties. Thus, in this study, we aimed to investigate the therapeutic effects and detailed mechanisms of IS use against intestinal inflammation using both in vivo and in vitro models.


C57BL/6 mice were randomly divided into sham, dextran sodium sulfate (DSS), and DSS+IS groups. Colitis was established using 3.0% DSS through oral gavage for five consecutive days. In vitro, tumor necrosis factor-α (TNF-α)-treated Caco-2 cells were used as an inflammatory model. Clinical characteristics, histological performance, proinflammatory cytokine expression, and intestinal barrier function were measured. In addition, activation of the pyruvate dehydrogenase kinase 1/protein kinase B/nuclear factor-κB (PDK1/AKT/NF-κB) signaling pathway was determined by western blotting, quantitative polymerase chain reaction, and immunofluorescence assays.


IS mitigated DSS-induced colitis by significantly reducing body weight loss, colonic shortening, and the disease activity index score via inhibition of colonic proinflammatory cytokine production of IL-1β, IL-6, and TNF-α. IS restored impaired barrier function by regulating tight junctions and intestinal epithelial barrier permeability. Furthermore, we found that IS ameliorated intestinal barrier injury by regulating the PDK1-dependent AKT/NF-κB signaling pathway.


Our results demonstrate that IS attenuates experimental colitis by preserving intestinal barrier function, probably mediated by the PDK1/AKT/NF-κB signaling pathway. These findings highlight the potential of IS as a novel therapeutic agent for IBD.