Department of Biochemistry, Dongguk University College of Oriental Medicine, 707 Seokjang-dong, Gyeongju-si, Gyeongsangbuk-do 780-714, Gyeongju, Republic of Korea.
Atherosclerosis. 2010 Jul;211(1):77-83. doi: 10.1016/j.atherosclerosis.2010.01.040. Epub 2010 Feb 4.
Inflammation plays a critical role in the development of atherosclerosis and TNF-alpha, a major inflammatory cytokine, induces inflammatory responses by enhancing the expression of adhesion molecules and the secretion of inflammatory mediators. Indirubin is an active compound of Polygonum tinctorium Lour (P. tinctorium) that has the ability to suppress inflammation. Previously, we described the novel indirubin derivative, 5'-nitro-indirubinoxime (5'-NIO), and demonstrated that it has potent anti-proliferative activity against various human cancer cells. In this study, we examined the effect of 5'-NIO on the TNF-alpha induced inflammatory conditions of human umbilical vein endothelial cells (HUVECs). We found that 5'-NIO inhibited TNF-alpha induced MCP-1 and IL-8 expression at the RNA and protein levels in HUVECs. Specifically, 5'-NIO significantly inhibited the TNF-alpha stimulated release of MCP-1 and IL-8, with levels that were only 19.8% and 30.9% of those of untreated control cells, respectively. Furthermore, 5'-NIO largely inhibited the adhesion of U937 cells to HUVECs by decreasing the expression level of ICAM-1 and VCAM-1. Overall, these observations suggest that 5'-NIO has the potential for use as an anti-atherosclerotic agent.
炎症在动脉粥样硬化的发生发展中起着关键作用，肿瘤坏死因子-α（TNF-α）是一种主要的炎症细胞因子，通过增强黏附分子的表达和炎症介质的分泌来诱导炎症反应。靛玉红是蓼科植物蓼蓝（Polygonum tinctorium Lour）的活性成分，具有抑制炎症的能力。先前，我们描述了新型靛玉红衍生物 5'-硝基靛玉红肟（5'-NIO），并证实其对各种人类癌细胞具有很强的抗增殖活性。在本研究中，我们研究了 5'-NIO 对人脐静脉内皮细胞（HUVEC）中 TNF-α诱导的炎症条件的影响。结果发现，5'-NIO 可抑制 TNF-α诱导的 HUVEC 中 MCP-1 和 IL-8 的 RNA 和蛋白水平表达。具体而言，5'-NIO 可显著抑制 TNF-α刺激的 MCP-1 和 IL-8 的释放，其水平分别仅为未处理对照细胞的 19.8%和 30.9%。此外，5'-NIO 通过降低 ICAM-1 和 VCAM-1 的表达水平，显著抑制 U937 细胞与 HUVEC 的黏附。总之，这些观察结果表明，5'-NIO 具有作为抗动脉粥样硬化剂的潜力。
