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

Exp Eye Res. 2021 Jun:207:108586. doi: 10.1016/j.exer.2021.108586. Epub 2021 Apr 20.

Abstract

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 factor-2 (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.

Keywords: Erk1/2; Ginkgo biloba; Nrf2; Procyanidin B2; RPE cells; Rutin; anti-oxidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Biflavonoids / pharmacology*
  • Blotting, Western
  • Catechin / pharmacology*
  • Cell Survival
  • Cells, Cultured
  • Flow Cytometry
  • Ginkgo biloba / chemistry*
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Membrane Potential, Mitochondrial
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects*
  • Plant Extracts / chemistry*
  • Proanthocyanidins / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Rutin / pharmacology*
  • tert-Butylhydroperoxide / toxicity

Substances

  • Antioxidants
  • Biflavonoids
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Plant Extracts
  • Proanthocyanidins
  • Reactive Oxygen Species
  • procyanidin B2
  • Rutin
  • Catechin
  • tert-Butylhydroperoxide