Li Yanli, Liu Jie, Pongkorpsakol Pawin, Xiong Zhengguo, Li Li, Jiang Xuemei, Zhao Haixia, Yuan Ding, Zhang Changcheng, Guo Yuhui, Dun Yaoyan
Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, Medical College, China Three Gorges University, Yichang, China.
Department of Medical Research Center, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, China.
Front Pharmacol. 2022 Jun 8;13:903762. doi: 10.3389/fphar.2022.903762. eCollection 2022.
Inflammatory cytokines including TNF-α and IL-1β impair intestinal barrier function in aging by disrupting intestinal tight junction integrity. Icariin (ICA) has a variety of pharmacological effects. Indeed, ICA produces anti-inflammatory, anti-oxidative stress, and inhibitory effects on microRNA (miRNA) expression. This study was to explore whether ICA could alleviate inflammation-associated intestinal barrier function impairment in aging and its underlying mechanism. Of particular interest, network pharmacology prediction indicated the potential therapeutic impacts of ICA for the treatment of colitis. Then, rats were used to study whether ICA has a protective effect on the reduction of tight junctions caused by inflammatory cytokines. Next, Caco-2 cell monolayers were used to explore the mechanism by which ICA alleviates the down-regulation of tight junctions. Network pharmacology prediction revealed that ICA alleviated colitis suppressing oxidative stress. After ICA intervention, expressions of inflammatory cytokines were reduced, but tight junctions, antioxidant enzymes in aging rats were up-regulated. ICA reversed the TNF-α-induced decrease in abundance of Occludin protein in Caco-2 cell monolayers. Meanwhile, ICA alleviated the increase in permeability and expression of miR-122a. However, the protective effect of ICA was markedly attenuated after transfection with miR-122a mimics. In conclusion, ICA reduced the expressions of Occludin, Claudin1, and Claudin5 in colon, which were related to the reduction of TNF-α and IL-1β and alleviation of colonic in . And ICA attenuated TNF-α-induced Occludin disruption and epithelial barrier impairment by decreasing miR-122a expression in Caco-2 cell monolayers.
包括肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）在内的炎性细胞因子通过破坏肠道紧密连接完整性损害衰老过程中的肠道屏障功能。淫羊藿苷（ICA）具有多种药理作用。实际上，ICA具有抗炎、抗氧化应激以及对微小RNA（miRNA）表达的抑制作用。本研究旨在探讨ICA是否能减轻衰老过程中与炎症相关的肠道屏障功能损害及其潜在机制。特别值得关注的是，网络药理学预测表明ICA对结肠炎治疗具有潜在的治疗作用。然后，使用大鼠研究ICA对炎性细胞因子引起的紧密连接减少是否具有保护作用。接下来，使用Caco-2细胞单层来探究ICA减轻紧密连接下调的机制。网络药理学预测显示ICA通过抑制氧化应激减轻结肠炎。ICA干预后，衰老大鼠体内炎性细胞因子的表达降低，但紧密连接、抗氧化酶上调。ICA逆转了TNF-α诱导的Caco-2细胞单层中闭合蛋白（Occludin）蛋白丰度的降低。同时，ICA减轻了通透性增加和miR-122a的表达。然而，用miR-122a模拟物转染后，ICA的保护作用明显减弱。总之，ICA降低了结肠中Occludin、Claudin1和Claudin5的表达，这与TNF-α和IL-1β的减少以及结肠炎症的减轻有关。并且ICA通过降低Caco-2细胞单层中miR-122a的表达减轻了TNF-α诱导的Occludin破坏和上皮屏障损伤。
