Cyanidin-3-glucoside attenuates 4-hydroxynonenal- and visible light-induced retinal damage in vitro and in vivo.

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.

[1]  A. Kauppinen,et al.  SQSTM1/p62 regulates the production of IL‐8 and MCP‐1 in IL‐1&bgr;‐stimulated human retinal pigment epithelial cells , 2019, Cytokine.

[2]  K. Kaarniranta,et al.  Dietary Polyphenols in Age-Related Macular Degeneration: Protection against Oxidative Stress and Beyond , 2019, Oxidative medicine and cellular longevity.

[3]  M. Cao,et al.  Blueberry Polyphenols Ameliorate Visible Light and Lipid-Induced Injury of Retinal Pigment Epithelial Cells. , 2018, Journal of agricultural and food chemistry.

[4]  J. Jee,et al.  4‐Hydroxynonenal‐induced GPR109A (HCA2 receptor) activation elicits bipolar responses, Gαi‐mediated anti‐inflammatory effects and Gβγ‐mediated cell death , 2018, British journal of pharmacology.

[5]  B. Ji,et al.  Dietary supplementation with omega-3 polyunsaturated fatty acid-rich oils protects against visible-light-induced retinal damage in vivo. , 2018, Food & function.

[6]  Shuhei Yamada,et al.  Visualization of the distribution of anthocyanin species in mice eyeball by matrix-assisted laser desorption/ionization mass spectrometry imaging. , 2018, Rapid communications in mass spectrometry : RCM.

[7]  Z. Sui,et al.  Antioxidant and Anti-Inflammatory Effects of Blueberry Anthocyanins on High Glucose-Induced Human Retinal Capillary Endothelial Cells , 2018, Oxidative medicine and cellular longevity.

[8]  B. Burton-Freeman,et al.  The effect of dietary factors on strawberry anthocyanins oral bioavailability. , 2017, Food & function.

[9]  M. Tanito,et al.  Lipid radicals cause light-induced retinal degeneration. , 2017, Chemical communications.

[10]  W. Ling,et al.  Cyanidin-3-O-β-glucoside protects against liver fibrosis induced by alcohol via regulating energy homeostasis and AMPK/autophagy signaling pathway , 2017 .

[11]  J. Sparrow,et al.  Quercetin and cyanidin‐3‐glucoside protect against photooxidation and photodegradation of A2E in retinal pigment epithelial cells , 2017, Experimental eye research.

[12]  B. Ji,et al.  Protective effect of quercetin and chlorogenic acid, two polyphenols widely present in edible plant varieties, on visible light-induced retinal degeneration in vivo , 2017 .

[13]  R. Hogg,et al.  Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8) , 2017, Journal of Neuroinflammation.

[14]  E. Gaillard,et al.  The Anthocyanins, Oenin and Callistephin, Protect RPE Cells Against Oxidative Stress , 2017, Photochemistry and photobiology.

[15]  B. Ji,et al.  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. , 2016, Molecular nutrition & food research.

[16]  M. C. Naranjo,et al.  Postprandial dietary fatty acids exert divergent inflammatory responses in retinal-pigmented epithelium cells. , 2016, Food & function.

[17]  S. de Pascual-Teresa,et al.  A protective effect of anthocyanins and xanthophylls on UVB-induced damage in retinal pigment epithelial cells. , 2016, Food & function.

[18]  B. Ji,et al.  Retinoprotective Effects of Bilberry Anthocyanins via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms in a Visible Light-Induced Retinal Degeneration Model in Pigmented Rabbits , 2015, Molecules.

[19]  A. Kauppinen,et al.  Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation , 2015, Scientific Reports.

[20]  F. Holz,et al.  Complement Component C5a Primes Retinal Pigment Epithelial Cells for Inflammasome Activation by Lipofuscin-mediated Photooxidative Damage* , 2015, The Journal of Biological Chemistry.

[21]  B. Ji,et al.  The protective effects of berry-derived anthocyanins against visible light-induced damage in human retinal pigment epithelial cells. , 2015, Journal of the science of food and agriculture.

[22]  A. Salminen,et al.  Quercetin alleviates 4-hydroxynonenal-induced cytotoxicity and inflammation in ARPE-19 cells. , 2015, Experimental eye research.

[23]  H. Hara,et al.  Protective effects of bilberry and lingonberry extracts against blue light-emitting diode light-induced retinal photoreceptor cell damage in vitro , 2014, BMC Complementary and Alternative Medicine.

[24]  B. Yaspan,et al.  Mechanisms of age‐related macular degeneration and therapeutic opportunities , 2014, The Journal of pathology.

[25]  T. Preston,et al.  Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13)C-tracer study. , 2013, The American journal of clinical nutrition.

[26]  J. Nowak.  Oxidative stress, polyunsaturated fatty acids-derived oxidation products and bisretinoids as potential inducers of CNS diseases: focus on age-related macular degeneration , 2013, Pharmacological reports : PR.

[27]  I. Bhutto,et al.  Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. , 2012, Molecular aspects of medicine.

[28]  S. Jarrett,et al.  Consequences of oxidative stress in age-related macular degeneration. , 2012, Molecular aspects of medicine.

[29]  K. Tsubota,et al.  Biological role of lutein in the light-induced retinal degeneration. , 2012, The Journal of nutritional biochemistry.

[30]  David H. Sliney,et al.  The susceptibility of the retina to photochemical damage from visible light , 2012, Progress in Retinal and Eye Research.

[31]  R. Vatsyayan,et al.  Role of 4-hydroxynonenal in epidermal growth factor receptor-mediated signaling in retinal pigment epithelial cells. , 2011, Experimental eye research.

[32]  S. Qin,et al.  Differential roles of AMPKα1 and AMPKα2 in regulating 4-HNE-induced RPE cell death and permeability. , 2010, Experimental eye research.

[33]  D. Hicks,et al.  The retinal pigment epithelium in health and disease. , 2010, Current molecular medicine.

[34]  J. Tuo,et al.  The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice. , 2010, Experimental eye research.

[35]  J. Kopitz,et al.  Effects of lipid peroxidation products on lipofuscinogenesis and autophagy in human retinal pigment epithelial cells. , 2010, Experimental eye research.

[36]  D. K. Vaughan,et al.  Retinal light damage: Mechanisms and protection , 2010, Progress in Retinal and Eye Research.

[37]  A. Kampik,et al.  Subtoxic oxidative stress induces senescence in retinal pigment epithelial cells via TGF-beta release. , 2009, Investigative Ophthalmology and Visual Science.

[38]  M. Bartoli,et al.  Vascular endothelial growth factor in eye disease , 2008, Progress in Retinal and Eye Research.

[39]  J. Blumberg,et al.  Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs. , 2008, Journal of agricultural and food chemistry.

[40]  M. Tanito,et al.  Protein modifications by 4-hydroxynonenal and 4-hydroxyhexenal in light-exposed rat retina. , 2005, Investigative ophthalmology & visual science.

[41]  Olaf Strauss,et al.  The retinal pigment epithelium in visual function. , 2005, Physiological reviews.

[42]  M. Boulton,et al.  RPE lipofuscin and its role in retinal pathobiology. , 2005, Experimental eye research.

[43]  K. Nakanishi,et al.  Anthocyanins Protect Against A2E Photooxidation and Membrane Permeabilization in Retinal Pigment Epithelial Cells¶ , 2005, Photochemistry and photobiology.

[44]  J. Kopitz,et al.  Proteins modified by malondialdehyde, 4-hydroxynonenal, or advanced glycation end products in lipofuscin of human retinal pigment epithelium. , 2003, Investigative ophthalmology & visual science.

[45]  M. Hirayama,et al.  Stimulatory effect of cyanidin 3-glycosides on the regeneration of rhodopsin. , 2003, Journal of agricultural and food chemistry.

[46]  S. Srivastava,et al.  Metabolism of lipid peroxidation product, 4-hydroxynonenal (HNE) in rat erythrocytes: role of aldose reductase. , 2000, Free radical biology & medicine.

[47]  K. Kaarniranta,et al.  Plant flavonol quercetin and isoflavone biochanin A differentially induce protection against oxidative stress and inflammation in ARPE-19 cells , 2011 .

[48]  H. Esterbauer,et al.  Chemistry and pathophysiology of oxidation of LDL. , 1996, Reviews of physiology, biochemistry and pharmacology.