Cyanidin-3-glucoside and its phenolic acid metabolites attenuate visible light-induced retinal degeneration in vivo via activation of Nrf2/HO-1 pathway and NF-κB suppression

• Published in: Molecular nutrition & food research 2016-07, Vol.60 (7), p.1564-1577
• Main Authors: Wang, Yong, Huo, Yazhen, Zhao, Liang, Lu, Feng, Wang, Ou, Yang, Xue, Ji, Baoping, Zhou, Feng
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes - metabolism; Animals; Anthocyanins - pharmacology; Antioxidants - pharmacology; Apoptosis - drug effects; Apoptosis - radiation effects; Coumaric Acids - pharmacology; Cyanidin-3-glucoside; Cytokines - genetics; Cytokines - metabolism; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Glucosides - pharmacology; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Hydroxybenzoates - pharmacology; In Situ Nick-End Labeling; Inflammation; Light - adverse effects; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - metabolism; Oxidative stress; Oxidative Stress - drug effects; Phenolic acid metabolites; Rabbits; Retina - drug effects; Retina - radiation effects; Retinal Degeneration - drug therapy; Retinal Degeneration - etiology; Retinoprotection; Signal Transduction; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Up-Regulation
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201501048

Scope 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. Methods and results 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. Conclusion 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. Cyanidin‐3‐glucoside (C3G) is a major anthocyanin in berries and a potential nutritional supplement for preventing retinal degeneration. Protocatechuic acid (PCA) and ferulic acid (FA) are the major human metabolites of C3G in plasma. C3G, PCA, and FA treatments protect the structure and function of photoreceptor cells from light‐induced retinal degeneration. 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, PCA, and FA attenuated the photooxidation‐induced apoptosis and angiogenesis in the retina.