cyanidin-3-o-beta-glucopyranoside and 4-hydroxy-2-nonenal

4-Hydroxynonenal (HNE) is a highly reactive end-product of lipid peroxidation reaction that leads to retinal pigment epithelial (RPE) cell damage. Cyanidin-3-glucoside (C3G), the most abundant anthocyanin in the edible parts of plants, is a nutritional supplement used for preventing retinal damage. However, the protective effect of C3G against HNE-induced RPE cell damage remains to be elucidated. The protective mechanisms of C3G on ARPE-19 cells after HNE exposure were investigated in this study. Results showed that compared with HNE-treated cells, the viability of ARPE-19 cells was significantly (P < 0.05) increased after 1 and 5 μM C3G treatment. C3G exhibited a significant (P < 0.05) inhibitory effect on the expression of senescence-associated β-galactosidase in ARPE-19 cells. VEGF levels in the C3G groups were significantly (P < 0.05) decreased relative to those of the HNE-treated group. C3G also regulated the release of two inflammatory mediators, namely monocyte chemoattractant protein 1 and interleukine-8, in ARPE-19 cells after HNE treatment. Furthermore, C3G attenuated retinal cell apoptosis in pigmented rabbits induced by visible light. Therefore, our data showed that C3G has efficient protective effects on HNE-induced apoptosis, angiogenesis, and dysregulated cytokine production in ARPE-19 cells.

Topics: Aldehydes; Animals; Anthocyanins; Apoptosis; Chemokine CCL2; Glucosides; Humans; Interleukin-8; Light; Rabbits; Retinal Diseases; Retinal Pigment Epithelium; Vascular Endothelial Growth Factor A

Cyanidin-3-glucoside (C3G) is a major anthocyanin in berries and a potential nutritional supplement for preventing retinal degeneration. However, the protective mechanism of C3G and its metabolites, protocatechuic acid (PCA) and ferulic acid (FA), remain unclear. The molecular mechanisms of C3G and its metabolites against retinal photooxidative damage in vivo are investigated.. Pigmented rabbits were orally administered C3G, PCA, and FA (0.11 mmol/kg/day) for 3 weeks. Electroretinography, histological analysis, and TUNEL assay showed that C3G and its metabolites attenuated retinal cell apoptosis. The expression of oxidative stress markers were upregulated after light exposure but attenuated by C3G and FA, which may be attributed to the elevated secretion and expression of heme oxygenase (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2). C3G, PCA, and FA attenuated the secretion or expression of inflammation-related genes; FA suppressed nuclear factor kappa B (NF-κB) activation. The treatments attenuated the light-induced changes on certain apoptotic proteins and angiogenesis-related cytokines.. C3G and FA reduced light-induced retinal oxidative stress by activating the Nrf2/HO-1 antioxidant pathway. FA attenuated the light-induced retinal inflammation by suppressing NF-κB activation. C3G and its metabolites attenuated the photooxidation-induced apoptosis and angiogenesis in the retina.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Anthocyanins; Antioxidants; Apoptosis; Coumaric Acids; Cytokines; Deoxyguanosine; Glucosides; Heme Oxygenase-1; Hydroxybenzoates; In Situ Nick-End Labeling; Light; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Rabbits; Retina; Retinal Degeneration; Signal Transduction; Tyrosine; Up-Regulation