Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. Gambogic acid has been reported to have anti-inflammatory effect. However, the effect of GA on inflammatory response of ARPE-19 cells remains unclear. In our study, ARPE-19 cells were stimulated by palmitic acid (PA) induction in the presence of 30 mM glucose and then treated with 0.5, 1, 2, 5, 10, or 20 μM GA. CCK-8 assay showed that cell viability was increased by GA treatment at doses of 0.5, 1, and 2 μM instead of higher doses. ELISA analysis found that GA dose-dependently reduced the production of pro-inflammatory mediators TNF-α and IL-1β. Western blot indicated that GA downregulated the expression of NLRP3 inflammasome components including TXNIP, NLRP3, ASC, cleaved-caspase-1, and cleaved-IL-1β in a dose-dependent manner. In addition, Western blot and immunofluorescence analysis suggested that GA effectively increased the protein level of nuclear factor E2-related factor-2 (Nrf2). RT-qPCR showed that GA significantly increased the mRNA levels of Heme oxygenase-1 (HO-1) and NADPH:quinone oxidoreductase1 (NQO1). Furthermore, Nrf2 siRNA transfection confirmed the above effects of GA. In total, subtoxic doses of GA significantly flattened the inflammatory response induced by HG and PA in ARPE-19 cells via modulating the Nrf2 signaling pathway.

糖尿病视网膜病变（DR）是糖尿病的一种严重的微血管并发症。据报道藤黄酸具有抗炎作用。然而，GA对ARPE-19细胞炎症反应的影响仍不清楚。在我们的研究中，在 30 mM 葡萄糖存在下通过棕榈酸 (PA) 诱导刺激 ARPE-19 细胞，然后用 0.5、1、2、5、10 或 20 μM GA 处理。 CCK-8 测定表明，0.5、1 和 2 μM 剂量的 GA 处理（而不是更高剂量）提高了细胞活力。 ELISA 分析发现，GA 剂量依赖性地减少促炎介质 TNF-α 和 IL-1β 的产生。 Western blot结果显示，GA以剂量依赖性方式下调NLRP3炎症小体成分的表达，包括TXNIP、NLRP3、ASC、cleaved-caspase-1和cleaved-IL-1β。此外，Western blot和免疫荧光分析表明，GA有效提高了核因子E2相关因子2（Nrf2）的蛋白水平。 RT-qPCR 显示，GA 显着增加了血红素加氧酶-1 (HO-1) 和 NADPH:醌氧化还原酶 1 (NQO1) 的 mRNA 水平。此外，Nrf2 siRNA转染证实了GA的上述效果。总的来说，亚毒性剂量的 GA 通过调节 Nrf2 信号通路，显着平缓了 ARPE-19 细胞中 HG 和 PA 诱导的炎症反应。