Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology & Business University, Beijing 100048, China.
J Immunol Res. 2018 Apr 30;2018:5604610. doi: 10.1155/2018/5604610. eCollection 2018.
Recently, the NLRP3 inflammasome activation in the eyes has been known to be associated with the pathogenesis of age-related macular degeneration. The aim of this study was to investigate the protective effects of cyanidin-3-glucoside (C3G), an important anthocyanin with great potential for preventing eye diseases, against 4-hydroxyhexenal- (HHE-) induced inflammatory damages in human retinal pigment epithelial cells, ARPE-19. We noticed that C3G pretreatment to the ARPE-19 cells rescued HHE-induced antiproliferative effects. Cell apoptosis ratio induced by HHE was also decreased by C3G, measured by flow cytometry. The activation of NLRP3 inflammasome induced by HHE was found with increases of caspase-1 activity, proinflammatory cytokine releases (IL-1 and IL-18), and NLRP3 inflammasome-related gene expressions (NLRP3, IL-1, IL-18, and caspase-1). The C3G showed potent inhibitive effects on these NLRP3 inflammasome activation hallmarks induced by HHE. Moreover, we noticed that the C3G's pretreatment leads to a delayed and a decreased JNK activation in HHE-challenged ARPE-19 cells. Finally, using a luciferase reporter gene assay system, we demonstrated that HHE-induced activation protein- (AP-) 1 transcription activity was abolished by C3G pretreatment in a dose-dependent manner. Taken together, these data showed that HHE leads to inflammatory damages to ARPE-19 cells while C3G has great protective effects, highlighting future potential applications of C3G against AMD-associated inflammation.
最近，人们已经知道，NLRP3 炎性小体在眼睛中的激活与年龄相关性黄斑变性的发病机制有关。本研究的目的是研究矢车菊素-3-葡萄糖苷（C3G）的保护作用，C3G 是一种具有预防眼部疾病巨大潜力的重要花色苷，对抗 4-羟基己醛（HHE）诱导的人视网膜色素上皮细胞（ARPE-19）炎症损伤。我们注意到，C3G 预处理 ARPE-19 细胞可挽救 HHE 诱导的增殖抑制作用。通过流式细胞术测量，HHE 诱导的细胞凋亡比例也因 C3G 而降低。发现 HHE 诱导 NLRP3 炎性小体的激活伴随着 caspase-1 活性、促炎细胞因子释放（IL-1 和 IL-18）和 NLRP3 炎性小体相关基因表达（NLRP3、IL-1、IL-18 和 caspase-1）的增加。C3G 对 HHE 诱导的这些 NLRP3 炎性小体激活标志物表现出强大的抑制作用。此外，我们注意到 C3G 的预处理导致 HHE 挑战的 ARPE-19 细胞中 JNK 激活延迟和减少。最后，使用荧光素酶报告基因检测系统，我们证明 C3G 预处理以剂量依赖的方式消除了 HHE 诱导的激活蛋白-1（AP-1）转录活性。综上所述，这些数据表明 HHE 导致 ARPE-19 细胞发生炎症损伤，而 C3G 具有强大的保护作用，突出了 C3G 对抗 AMD 相关炎症的未来潜在应用。
