Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, UK.
College of Biological and Environmental Engineering, Changsha University, Changsha, Hunan, 410022, PR China.
Exp Eye Res. 2020 Feb;191:107931. doi: 10.1016/j.exer.2020.107931. Epub 2020 Jan 10.
Age-related macular degeneration (AMD) is a predominant cause of visual deficit in aged population. Abnormal accumulation of cholesterol, including oxidized low-density lipoprotein (oxLDL), underneath the retinal pigment epithelium (RPE) cells contributes to the development of AMD. Gypenosides (Gyp) are glycosides extracted from Gynostemma pentaphyllum and have demonstrated protective effects against inflammation and oxidative stress. To determine the therapeutic potential of Gyp for AMD, we investigated its effect on cholesterol trafficking and metabolism and assessed the protective function of Gyp against oxLDL-induced damage in RPE cells. Cholesterol efflux to high-density lipoprotein (HDL) and human serum was significantly increased in RPE cells treated with Gyp when compared to untreated control cells. Expression of cholesterol metabolism (CYP27A1, CYP46A1) and trafficking (TSPO, ABCA1 and ABCG1) genes was also markedly increased in Gyp-treated RPE cells. OxLDL-treated RPE cells had significantly increased cholesterol accumulation and lipid droplet formation. There were marked increases in reactive oxygen species (ROS) generation and proinflammatory cytokines via NF-κB activation in RPE cells treated with oxLDL, while incubation with Gyp rectified these changes. These findings provide pharmacological evidence that Gyp has the potential to treat patients with early onset AMD by promoting cellular cholesterol removal from RPE cells and inhibiting inflammation and oxidative stress.
年龄相关性黄斑变性（AMD）是老年人群视力减退的主要原因。胆固醇的异常积累，包括氧化型低密度脂蛋白（oxLDL），在视网膜色素上皮（RPE）细胞下方积累，导致 AMD 的发生。绞股蓝苷（Gyp）是从绞股蓝中提取的糖苷，已被证明具有抗炎和抗氧化应激的保护作用。为了确定 Gyp 治疗 AMD 的潜力，我们研究了它对胆固醇转运和代谢的影响，并评估了 Gyp 对 oxLDL 诱导的 RPE 细胞损伤的保护作用。与未处理的对照细胞相比，用 Gyp 处理的 RPE 细胞中胆固醇向高密度脂蛋白（HDL）和人血清的流出显著增加。Gyp 处理的 RPE 细胞中胆固醇代谢（CYP27A1、CYP46A1）和转运（TSPO、ABCA1 和 ABCG1）基因的表达也明显增加。oxLDL 处理的 RPE 细胞中胆固醇积累和脂滴形成明显增加。oxLDL 处理的 RPE 细胞中活性氧（ROS）生成和促炎细胞因子通过 NF-κB 激活显著增加，而用 Gyp 孵育则纠正了这些变化。这些发现提供了药理学证据，表明 Gyp 通过促进 RPE 细胞中细胞胆固醇的清除以及抑制炎症和氧化应激，有可能治疗早期 AMD 患者。
