Department of Ophthalmology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, People's Republic of China.
Department of Ophthalmology, The Third People's Hospital of Jingdezhen, Jingdezhen, 333000, People's Republic of China.
J Biochem Mol Toxicol. 2018 May;32(5):e22052. doi: 10.1002/jbt.22052. Epub 2018 Apr 24.
Nobiletin (3',4',5,6,7,8-hexamethoxyflavone), a dietary polymethoxylated flavonoid found in Citrus fruits, has been reported to have antioxidant effect. However, the effect of nobiletin on human retinal pigment epithelium (RPE) cells induced by hydrogen peroxide (H O ) is still unclear. Therefore, we investigated the protective effect of nobiletin against H O -induced cell death in RPE cells. Our results demonstrated that nobiletin significantly increased cell viability from oxidative stress. Nobiletin inhibited H O -induced ROS production and caspase-3/7 activity in ARPE-19 cells. Furthermore, nobiletin significantly increased Akt phosphorylation in ARPE-19 cells exposed to H O . Meanwhile, LY294002, an inhibitor of PI3K/Akt, abolished the protective effect of nobiletin against H O -induced decreased cell viability and increased caspase-3/7 activity in ARPE-19 cells. In summary, these data show that nobiletin protects RPE cells against oxidative stress through activation of the Akt-signaling pathway. Thus, nobiletin should be an oxidant that attenuates the development of age-related macular degeneration.
川陈皮素（3'，4'，5，6，7，8-六甲氧基黄酮），一种存在于柑橘类水果中的饮食性多甲氧基类黄酮，已被报道具有抗氧化作用。然而，川陈皮素对过氧化氢（H2O2）诱导的人视网膜色素上皮（RPE）细胞的影响尚不清楚。因此，我们研究了川陈皮素对 H2O2 诱导的 RPE 细胞死亡的保护作用。我们的结果表明，川陈皮素可显著提高氧化应激下的细胞活力。川陈皮素抑制了 ARPE-19 细胞中 H2O2 诱导的 ROS 产生和 caspase-3/7 活性。此外，川陈皮素可显著增加 ARPE-19 细胞中 H2O2 诱导的 Akt 磷酸化。同时，PI3K/Akt 的抑制剂 LY294002 消除了川陈皮素对 H2O2 诱导的 ARPE-19 细胞活力下降和 caspase-3/7 活性增加的保护作用。总之，这些数据表明，川陈皮素通过激活 Akt 信号通路来保护 RPE 细胞免受氧化应激。因此，川陈皮素应该是一种可以减轻年龄相关性黄斑变性发展的氧化剂。
