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.

中文翻译：

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绞股蓝总皂甙介导胆固醇外流并抑制氧化的LDL诱导的视网膜色素上皮细胞炎症。

年龄相关性黄斑变性（AMD）是老年人口视力缺陷的主要原因。视网膜色素上皮细胞（RPE）下方胆固醇的异常积累，包括氧化的低密度脂蛋白（oxLDL），有助于AMD的发展。绞股蓝甙（Gyp）是从绞股蓝（Gynostemma pentaphyllum）中提取的糖苷，对炎症和氧化应激具有保护作用。为了确定Gyp对AMD的治疗潜力，我们调查了其对胆固醇运输和代谢的影响，并评估了Gyp对oxLDL诱导的RPE细胞损伤的保护功能。与未处理的对照细胞相比，在用Gyp处理的RPE细胞中，胆固醇向高密度脂蛋白（HDL）和人血清的外排显着增加。在经Gyp处理的RPE细胞中，胆固醇代谢（CYP27A1，CYP46A1）和运输（TSPO，ABCA1和ABCG1）基因的表达也显着增加。OxLDL处理的RPE细胞具有显着增加的胆固醇积累和脂质滴形成。在用oxLDL处理的RPE细胞中，通过NF-κB活化，活性氧（ROS）的产生和促炎细胞因子显着增加，而与Gyp孵育可纠正这些变化。这些发现提供了药理学证据，表明Gyp有潜力通过促进RPE细胞中细胞胆固醇的清除以及抑制炎症和氧化应激来治疗早期AMD患者。OxLDL处理的RPE细胞具有显着增加的胆固醇积累和脂质滴形成。在用oxLDL处理的RPE细胞中，通过NF-κB活化，活性氧（ROS）的产生和促炎细胞因子显着增加，而与Gyp孵育可纠正这些变化。这些发现提供了药理学证据，表明Gyp有潜力通过促进RPE细胞中细胞胆固醇的清除以及抑制炎症和氧化应激来治疗早期AMD患者。OxLDL处理的RPE细胞具有显着增加的胆固醇积累和脂质滴形成。在用oxLDL处理的RPE细胞中，通过NF-κB活化，活性氧（ROS）的产生和促炎细胞因子显着增加，而与Gyp孵育可纠正这些变化。这些发现提供了药理学证据，表明Gyp有潜力通过促进RPE细胞中细胞胆固醇的清除以及抑制炎症和氧化应激来治疗早期AMD患者。