Curcumin analog C66 alleviates inflammatory colitis by inhibiting the activation of NF-κB

炎症性肠病 细胞凋亡 炎症 结肠炎 医学 NF-κB 脂多糖 肠易激综合征 内科学 化学 生物化学 疾病
作者
Chenghong Hu,Yue Chen,Lingxi Zhang,Min Liu,Jie Yang,Fang Huang,Yi Wang,Lijiang Huang
出处
期刊:Inflammopharmacology [Springer Nature]
卷期号:30 (6): 2167-2179 被引量:4
标识
DOI:10.1007/s10787-022-01085-w
摘要

BackgroundThe pathogenesis of inflammatory bowel disease (IBD) remains unclear. C66, a derivative of curcumin, reportedly exerts anti-inflammatory, antifibrotic and anti-apoptotic effects by targeting the JNK pathway. However, the effect of C66 against IBD is not clear. In this study, we aimed to investigate the effect of C66 against IBD.MethodsC57BL/6J mice were treated with 2.5% DSS for 7 days, and then administered water for 3 days to develop the IBD mouse model. A mouse intestinal epithelial cell line, MODE-K, stimulated by lipopolysaccharide (LPS) was used as the in vitro model. The therapeutic effects of C66 were evaluated and the pharmacological mechanisms were explored.ResultsCompared to the model group, C66 treatment significantly reduced colitis-associated damage, including a decrease in disease activity index (DAI), a higher body weight and longer colon. In addition, the infiltration of distal inflammatory cells, loss of crypt tissues, and destruction of epithelial cells were reduced in C66-treated group. In addition, C66 treatment reduced fibrotic areas and inflammatory responses in the colon tissues, leading to increased epithelial cell proliferation and decreased apoptosis in colon. Furthermore, C66 treatment decreased the levels of p-JNK and p-P65, indicating that C66 inhibits the activation of the JNK and NF-κB signaling pathways induced by DSS in colon tissues. Finally, in vitro data show that C66 inhibited LPS-induced inflammation and apoptosis in small intestinal epithelial cells. ConclusionsThe curcumin analog C66 exhibits its anti-inflammatory effect by inhibiting the DSS-induced activation of JNK/NF-κB signaling pathways. C66 may be a potential candidate for the treatment of IBD.Graphical Abstract
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