Ginkgo biloba extracts (GBE) protect human RPE cells from t-BHP-induced oxidative stress and necrosis by activating the Nrf2-mediated antioxidant defence

Abstract

Abstract Objectives Age-related macular degeneration (AMD) is a prevalent ocular disease. Dry AMD accounts for most cases of blindness associated with AMD but there are no treatments. Oxidative stress-induced damage to retinal pigment epithelial (RPE) cells is a major contributor to the pathogenesis of dry AMD. This study investigated the protective actions of Ginkgo biloba extracts (GBE) in human RPE cells subjected to tert-butyl hydroperoxide (t-BHP)-mediated oxidative stress. Methods The human ARPE-19 cells were pre-treated with or without GBE before the exposure to t-BHP. Cell viability, cell death profile and lipid peroxidation were assessed. The findings were verified using human primary RPE cultures. Key findings GBE pre-treatment prevented the increase in lipid peroxidation and necrosis/ferroptosis, and the concurrent viability decrease in RPE cells exposed to t-BHP. It enabled the pronounced activation of Nrf2 and its downstream genes. We found that ERK1/2 phosphorylation was increased to a similar extent by t-BHP and GBE. Conclusion This study revealed that GBE pre-treatment attenuates pro-oxidant stress and protects human RPE cells from oxidative injury by modulating ERK1/2-Nrf2 axis. These findings suggest that GBE has the potential to be developed as a agent that may be valuable in decreasing AMD progression.