Nobiletin protects human retinal pigment epithelial cells from hydrogen peroxide-induced oxidative damage.

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 (H2 O2 ) is still unclear. Therefore, we investigated the protective effect of nobiletin against H2 O2 -induced cell death in RPE cells. Our results demonstrated that nobiletin significantly increased cell viability from oxidative stress. Nobiletin inhibited H2 O2 -induced ROS production and caspase-3/7 activity in ARPE-19 cells. Furthermore, nobiletin significantly increased Akt phosphorylation in ARPE-19 cells exposed to H2 O2 . Meanwhile, LY294002, an inhibitor of PI3K/Akt, abolished the protective effect of nobiletin against H2 O2 -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.