Evaluation of synergistic antioxidant interactions of lutein and cyanidin-3-O-glucoside and their roles in age-related macular degeneration

This study aimed to evaluate the effects of lutein (LUT) combined with cyanidin-3-O-glucoside (C3G) on age-related macular degeneration (AMD). Three complementary models were used to investigate the antioxidant effects, including free radical scavenging models, a cell model, and a mouse gavage assay. The results revealed that LUT combined with C3G at molar ratios ranging from 1:2 to 1:5 exhibited synergistic antioxidant effects in vitro. Compared with LUT/C3G alone, LUT:C3G (1:5) increased superoxide dismutase (SOD) and catalase (CAT) activities by 50.22%, 33.73% and 86.21%, 30.77%, respectively, increased glutathione (GSH) levels by 79.31% and 36.82%, and decreased malondialdehyde (MDA) levels by 50.04% and 31.11%. The combination treatment increased the mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) and decreased the level of Kelch-like ECH-associated protein 1 (Keap1). Furthermore, Nrf2 knockdown in ARPE-19 cells significantly inhibited combination treatment-induced Nrf2 protein expression and nuclear translocation, as well as HO-1 and NQO1 expression. A mouse model of AMD demonstrated that LUT combined with C3G activated the Keap1/Nrf2/HO-1/NQO1 signalling pathway, thereby preventing retinal oxidative stress.