Abstract

Nobiletin(3',4',5,6,7,8-hexamethoxyflavone), a dietary polymethoxylated flavonoid found inCitrusfruits, 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.

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