The Antioxidant Procyanidin Reduces Reactive Oxygen Species Signaling in Macrophages and Ameliorates Experimental Colitis in Mice.
The Antioxidant Procyanidin Reduces Reactive Oxygen Species Signaling in Macrophages and Ameliorates Experimental Colitis in Mice.
复制标题
抗氧化剂原花青素可减少巨噬细胞中的活性氧信号传导并改善小鼠实验性结肠炎
DOI：
10.3389/fimmu.2017.01910
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发表时间：
2017
影响因子：
7.3
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Chen L;You Q;Hu L;Gao J;Meng Q;Liu W;Wu X;Xu Q
炎症性肠病（IBD）的管理是一个真实的临床挑战。尽管进行了深入的研究，IBD的机制仍然基本上未被确定。据报道，一些炎性条件，如基质金属蛋白酶（MMPs）和核因子-κB（NF-κB）和NOD样受体蛋白3（NLRP 3）炎性信号传导通路，有助于IBD的发展和维持。调节其共同的上游信号，即活性氧（ROS），可能对控制IBD的进展很重要。在本研究中，我们发现，原花青素，一个强大的抗氧化黄酮类化合物，具有显着的效果，清除活性氧对THP-1巨噬细胞在脂多糖（LPS）或LPS结合的三磷酸腺苷刺激后，从而下调MMP 9的表达，抑制NF-κB信号，并中断NLRP 3炎性体的形成。此外，我们的体内数据显示，原花青素以剂量依赖性方式通过抑制小鼠结肠组织中MMP 9、NF-κB和NLRP 3炎性体信号传导的表达来减轻葡聚糖硫酸钠诱导的实验性结肠炎。总体而言，我们的研究结果表明，靶向ROS可能是结肠炎症的潜在治疗选择。
Management of inflammatory bowel disease (IBD) is a real clinical challenge. Despite intense investigation, the mechanisms of IBD remain substantially unidentified. Some inflammatory conditions, such as matrix metalloproteinases (MMPs) and the nuclear factor-κB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathways, are reported to contribute to the development and maintenance of IBD. Regulation of their common upstream signaling, that is, reactive oxygen species (ROS), may be important to control the progression of IBD. In the present study, we found that procyanidin, a powerful antioxidation flavonoid, has a significant effect on ROS clearance on THP-1 macrophages after lipopolysaccharide (LPS) or LPS-combined adenosine triphosphate stimulation, thus downregulating MMP9 expression, suppressing NF-κB signaling, and interrupting the formation of the NLRP3 inflammasome. Moreover, our in vivo data showed that procyanidin attenuated Dextran sulfate sodium-induced experimental colitis in a dose-dependent fashion by suppressing the expression of MMP9, NF-κB, and NLRP3 inflammasome signaling in colonic tissues in mice. Overall, our results suggested that targeting ROS could be a potential therapeutic choice for colonic inflammation.