Piceatannol Protects Human Retinal Pigment Epithelial Cells against Hydrogen Peroxide Induced Oxidative Stress and Apoptosis through Modulating PI3K/Akt Signaling Pathway

• Main Authors: Yiming Hao, Jie Liu, Ziyuan Wang, Liangli (Lucy) Yu, Jing Wang
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Nutrients
• Subjects: piceatannol; ARPE-19 cell; oxidative stress; apoptosis; PI3K/Akt signaling pathway
• Online Access: https://www.mdpi.com/2072-6643/11/7/1515

This study investigated the protective effect and the molecular mechanism of piceatannol on hydrogen peroxide (H₂O₂)-induced retinal pigment epithelium cell (ARPE-19) damage. Piceatannol treatment significantly inhibited H₂O₂-induced RPE cell death and reactive oxygen species (ROS) generation by 64.4% and 75.0%, respectively. Results of flow cytometry showed that H₂O₂-induced ARPE-19 cells apoptosis was ameliorated by piceatannol supplementation, along with decreased relative protein expressions of Bax/Bcl-2, Cleave-Caspase-3, and Cleave-PARP. Moreover, piceatannol treatment induced NF-E2-related factor 2 (Nrf2) signaling activation, which was evidenced by increased transcription of anti-oxidant genes, glutamate-cysteine ligase catalytic subunit (GCLc), SOD, and HO-1. Knockdown of Nrf2 through targeted siRNA alleviated piceatannol-mediated HO-1 transcription, and significantly abolished piceatannol-mediated cytoprotection. LY294002 (PI3K inhibitor) dramatically blocked piceatannol-mediated increasing of Nrf2 nuclear translocation, HO-1 expression, and cytoprotective activity, indicating the involvement of PI3K/Akt pathway in the cytoprotective effect of piceatannol. The results from this suggest the potential of piceatannol in reducing the risk of age-related macular degeneration.