Genipin protects against H 2 O 2 -induced oxidative damage in retinal pigment epithelial cells by promoting Nrf2 signaling

Abstract

Oxidative stress serves a vital function in the pathogenesis of age-related macular degeneration (AMD); genipin (GP) possesses antioxidative properties. The present study aimed to investigate the effects of GP on retinal pigment epithelial (RPE) cells induced by H 2 O 2 and the underlying mechanism. ARPE-19 cells were subjected to H 2 O 2 treatment to induce oxidative damage. Cell viability was determined via an MTT assay. Reactive oxygen species (ROS) levels and cell apoptosis were detected by flow cytometry. Nuclear factor-erythroid 2-related factor-2 (Nrf2) signaling-associated and the expression of apoptosis-associated factors were measured using reverse transcription-quantitative polymerase chain reaction assay and western blotting. The results revealed that 200 µM H 2 O 2 and 30 µM GP were determined to be the optimal concentrations for subsequent experimentation. GP reversed the inhibitory effects of H 2 O 2 by promoting cell viability, attenuating ROS accumulation and cell apoptosis, and increased the expression of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: Quinine oxidoreductase 1 (NQO1); Nrf2 silencing inhibited HO-1 and NQO1 expression. In addition, Nrf2 silencing enhanced the effects of H 2 O 2 by promoting ROS production and cell apoptosis. Compared with H 2 O 2 , Nrf2 silencing further decreased the expression levels of B-cell lymphoma-2 (Bcl-2), but increased that of Bcl-2-associated X protein and cleaved-caspase-3. The results of the present study revealed that Nrf2 silencing attenuated the protective effects of GP on H 2 O 2 -induced injury in ARPE-19 cells by promoting apoptosis and oxidation. Collectively, GP attenuated oxidative damage induced by H 2 O 2 in ARPE-19 cells. Furthermore, the molecular mechanism may be associated with the Nrf2 signaling pathway. The findings of the present study nay provide insight into a potential therapeutic agent for the treatment of AMD.