Citropten 通过阻断 NF-κB 和 JAK/STAT3 通路来缓解急性和复发性结肠炎。
Citropten alleviates acute and recurrent colitis via blockage of NF-κB and JAK/STAT3 pathways.
发表日期:2023 Nov 01
作者:
Yu Zhen Tang, Ying Liu, Ya Ping Chen, Ting Ting Feng, Ya Yi Liu, Yan Wang, Jun Ping Zhang, Wei Heng Xu
来源:
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要:
炎症性肠病(IBD)是一种以炎症为特征的慢性炎症性肠病,具有腹泻、腹痛、便血、体重减轻等多种症状。该病很难完全治愈,迫切需要有前景的候选治疗药物。 Citropten 是一种香豆素类化合物,存在于佛手果、羌活根和柑橘皮等中药中,已被证明可以抑制肿瘤细胞的增殖,预防抑郁症并抑制炎症介质的产生。在这项研究中,我们证明西托普汀可以减轻右旋糖酐硫酸钠(DSS)诱导的小鼠急性和复发性结肠炎,显着改善体重减轻、疾病活动指数、缩短结肠长度和组织学变化。此外,citropten 显着减少结肠组织中促炎介质的产生,并有效抑制脾脏中 Th17 细胞的比例。机制研究表明,citropten 显着抑制 NF-κB 和 JAK/STAT3 信号通路的激活,从而减少炎症、Th17 细胞和缓解结肠炎。这些发现为 Citropten 的抗结肠炎作用提供了新的见解,citropten 可能是治疗 IBD 的有前途的候选药物。版权所有 © 2023。由 Elsevier B.V. 出版。
Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease, which is characterized by inflammation, with many symptoms including diarrhea, abdominal pain, bloody stool, and weight loss. It is difficult to completely cure and promising therapeutic drug candidates are urgently needed. Citropten, a coumarin-like compound found in traditional Chinese medicine such as Finger Citron Fruit, notopterygium root and citrus peel, has been shown to inhibit the proliferation of tumor cells, protect against depression and suppress the production of inflammatory mediators. In this study, we demonstrated that citropten could alleviate dextran sulfate sodium (DSS)-induced acute and recurrent colitis in mice, with significant improvement in body weight loss, disease activity index, shortened colon length and histological changes. Moreover, citropten dramatically decreased the production of pro-inflammatory mediators in colon tissues and effectively suppressed the proportion of Th17 cells in spleen. Mechanism investigations revealed that citropten significantly inhibited the activation of NF-κB and JAK/STAT3 signaling pathways, thus leading to decreased inflammation, Th17 cells and alleviative colitis. These findings provide novel insights into the anti-colitis effect of citropten, which may be a promising drug candidate for treatment of IBD.Copyright © 2023. Published by Elsevier B.V.