Comparative Effects of Resveratrol and Delphinidin on Oxidative Stress, DNA Damage and VEGF Expression in ARPE-19 Cells

Background: Oxidative stress and DNA damage in retinal pigment epithelial (RPE) cells are major contributors to the development and progression of age-related macular degeneration (AMD). Natural polyphenolic compounds with antioxidant, anti-apoptotic, and anti-angiogenic properties may offer therapeutic benefits by protecting RPE cells against oxidative injury. This study aimed to compare the protective effects of resveratrol and delphinidin on oxidative stress, DNA damage, and vascular endothelial growth factor (VEGF) expression in ARPE-19 cells exposed to hydrogen peroxide (H₂O₂). Methods: ARPE-19 cells were cultured under standard conditions and divided into eight groups including (1) control (untreated), (2) hydrogen peroxide (H₂O₂)-treated to induce oxidative stress, (3) resveratrol alone, (4) H₂O₂ + resveratrol, (5) delphinidin alone, (6) H₂O₂ + delphinidin, (7) resveratrol + delphinidin, and (8) H₂O₂ + resveratrol + delphinidin. This grouping allowed for the assessment of each compound’s individual and combined effects, both in the presence and absence of oxidative stress. Biochemical assays including VEGF-A, 8-hydroxy-2′-deoxyguanosine (8-OHdG), poly(ADP-ribose) polymerase-1 (PARP-1), glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), and apoptosis were evaluated in each group. Results: Both delphinidin and resveratrol significantly reduced VEGF-A and MDA levels compared to the H₂O₂ group. Delphinidin was more effective than resveratrol in reducing TOS and apoptosis while enhancing TAS, GSH, and GSH-Px levels. Furthermore, delphinidin showed greater efficacy in lowering PARP-1 and 8-OHdG levels, indicating stronger protection against DNA damage. Combined treatment did not show superiority over delphinidin alone highlighting delphinidin’s potent standalone antioxidant and cytoprotective properties in ARPE-19 cells under oxidative stress. Conclusion: Delphinidin demonstrated superior antioxidant and cytoprotective effects compared to resveratrol in ARPE-19 cells exposed to oxidative stress. Its pronounced ability to suppress VEGF-A expression and attenuate DNA damage highlights its potential as a therapeutic agent for oxidative stress–related retinal diseases, particularly age-related macular degeneration (AMD).