Procyanidin B2 and rutin in Ginkgo biloba extracts protect human retinal pigment epithelial (RPE) cells from oxidative stress by modulating Nrf2 and Erk1/2 signalling

Oxidative stress plays an important role in the pathogenesis of human retinal diseases. Ginkgo biloba products are widely consumed herbal supplements that contain ingredients with anti-oxidant potentials. However, the active agents in ginkgo biloba extracts (GBE) are unclear. This study assessed the anti-oxidant effects of 19 natural compounds isolated from GBE to provide a rational basis for their use in preventing retinal diseases. The compounds were tested in retinal pigment epithelial (RPE) cells subjected to tert-butyl hydroperoxide (t-BHP)induced oxidative stress. Cell viability and intracellular reactive oxygen species (ROS) were assessed and flow cytometry was used to delineate the cell death profile. The expression of nuclear factor erythroid 2-related factor2 (Nrf2) was activated in RPE cells by t-BHP accompanied with an activation of Erk1/2 signaling. GBE-derived rutin and procyanidin B2 ameliorated t-BHP-induced cell death and promoted cell viability by suppressing intracellular ROS generation. These agents also enhanced Nrf2 expression with activating Erk1/2 signaling in RPE cells. In contrast, the other compounds tested were minimally active and did not prevent the loss of cell viability elicited by t-BHP. The present findings suggest that rutin and procyanidin B2 may have potential therapeutic values in the prevention of retinal diseases induced by oxidative damage.