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

Abstract

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.

Genipin protects against H2O2-induced oxidative damage in�retinal pigment epithelial cells by promoting Nrf2 signaling

“…Oxidative stress is one of the most important mechanisms underlying the pathogenesis of AMD (3). Oxidative damage of RPE is a key process in the pathogenesis of AMD (4). H 2 O 2 can induce the production of ROS in cells, leading to oxidative damage (23).…”

“…Oxidative stress serves a vital role in the pathogenesis of AMD (3). Retinal pigment epithelial (RPE) cells, as the most metabolically active type of cellin eye tissue, can engulf the outer disc of the retina photoreceptor cells and produce a large number of lipid peroxides and H 2 O 2 (4). Furthermore, the photo-oxidation effect occurs when RPE is illuminated over long durations (5).…”

Retinoid analogs and polyphenols as potential therapeutics for age-related macular degeneration

“…110 Nobiletin, a polymethoxylated flavonoid present in citrus fruits inhibited stress-induced activity of caspase-3/7 and significantly increased Akt phosphorylation in the ARPE-19 cells exposed to H 2 O 2 . 112 Wogonin, a methoxylated flavonoid with anxiolytic properties found in Scutellaria baicalensis, a common herb used in traditional Chinese medicine, 115 increased the viability of the ARPE-19 cells challenged with H 2 O 2 via modulation of the PI3K (phosphatidylinositol-3 kinase) and Akt pathway. 113,114 Together, all studies examining the effects of different flavonoids demonstrated that they possess the ability to mitigate the oxidative damage, reduce the activation of inflammatory markers, and can inhibit apoptosis, the fundamental processes related to AMD induction and progression.…”

“…Nobiletin, a polymethoxylated flavonoid present in citrus fruits inhibited stress-induced activity of caspase‐3/7 and significantly increased Akt phosphorylation in the ARPE-19 cells exposed to H 2 O 2 . 112…”

The Retinoid and Non-Retinoid Ligands of the Rod Visual G Protein-Coupled Receptor

“…The effects of flavonoids on the oxidative stress-induced cellular mortality have been evaluated broadly in vitro in the primary RPE-derived immortalized ARPE19 cells and photoreceptor-derived 661W cells subjected to hydrogen peroxide (H 2 O 2 ). Selected flavonoids such as kaemferol, nobiletin, eupatilin, hesperetin, and taxifolin showed protective effects against the oxidative insult with EC 50 in the low micromolar range, increasing cell viability and preventing cellular apoptosis [67][68][69][70].…”