促炎细胞因子
蛋白激酶B
势垒函数
结肠炎
信号转导
炎症性肠病
NF-κB
肿瘤坏死因子α
癌症研究
肠道通透性
PI3K/AKT/mTOR通路
炎症
细胞生物学
医学
免疫学
生物
内科学
疾病
作者
Yao Li,Xiaoli Chen,Manlu Shen,Yuan Zhao,Qian Cao
标识
DOI:10.1016/j.intimp.2022.109532
摘要
Inflammatory bowel diseases (IBD) are chronic debilitating inflammatory disorders 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. In this study, we aimed to investigate effects and mechanisms of IS against intestinal inflammation. C57BL/6 mice were randomly divided into Sham, IS, dextran sodium sulfate (DSS), and DSS + IS groups. In vivo colitis model was established using 3.0 % DSS. 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 and quantitative polymerase chain reaction. The results showed that IS mitigated DSS-induced colitis by reducing body weight loss, colonic shortening, and disease activity index score, and by inhibiting expressions of proinflammatory cytokines IL-1β, IL-6, and TNF-α. IS restored impaired barrier function by regulating tight junctions and intestinal epithelial permeability. Furthermore, we found that IS ameliorated intestinal barrier injury by regulating PDK1/AKT/NF-κB signaling pathway. In conclusion, our results demonstrate that IS attenuates experimental colitis by preserving intestinal barrier function, probably mediated by PDK1/AKT/NF-κB signaling pathway. These findings highlight the potential of IS as a therapeutic agent for IBD.
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