Taxifolin protects RPE cells against oxidative stress-induced apoptosis

Taxifolin was shown to protect RPE cells against oxidative stress-induced apoptosis. The potential mechanism appears to involve the activation of NRF2 and the phase II antioxidant enzyme system.

Human RPE (ARPE-19) cells were treated with different concentrations of taxifolin and 0.4 mM of H2O2 for 24 h. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was quantitatively measured by annexin V/propidium iodide double staining, and the expression levels of poly (ADP-ribose) polymerase (PARP) were evaluated by western blotting. Reactive oxygen species (ROS) were measured using a commercially available ROS detection system. The expressions of phase II enzymes, including NAD(P)H quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase modifier (GCLM) and catalytic (GCLC) subunits, were examined using real-time PCR and western blotting. The nuclear localization of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) protein was detected by western blotting.

Oxidative stress-induced damage to RPE cells has been suggested to be an important factor in the pathogenesis of age-related macular degeneration. Taxifolin, a flavonol, has been shown to exhibit significant antioxidant properties. The purpose of this study was to investigate the potential protective effects of taxifolin on RPE cells cultured under oxidative stress conditions and to elucidate the underlying mechanisms.

Taxifolin clearly inhibited the decrease in H2O2-induced cell viability, cell apoptosis, and intracellular ROS generation. In addition, taxifolin inhibited the H2O2-induced PARP cleavage. Moreover, treatment with taxifolin activated mRNA and the protein expression of NRF2 by inducing the translocation of NRF2 to the nucleus. Consequently, the mRNA and protein levels of the phase II enzymes NQO1, HO-1, GCLM, and GCLC increased. Conclusions: Taxifolin was shown to protect RPE cells against oxidative stress-induced apoptosis. The potential mechanism appears to involve the activation of NRF2 and the phase II antioxidant enzyme system.