An increase in oxidative stress plays a key role in neurotoxicity induction and cell death, which leads to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Cyanidin-3-glucoside (C3G) is a common anthocyanin and shows antioxidant activity in neuronal cells. Silent information regulator 2-related protein 1 (Sirt1) regulates antioxidant and anti-inflammatory effects. However, the effects of C3G on Sirt1 in neuronal cells remain unclear. This study evaluated the effect of C3G on Sirt1 expression and activity in human neuroblastoma (SH-SY5Y) cells. In the study, C3G increased the expression of Sirt1 and Sirt1 activity in SH-SY5Y cells. Additionally, C3G increased the expression of nuclear factor erythroid 2-related factor 2, a vital transcription factor for regulating the expression of antioxidant genes, as well as antioxidant enzymes such as superoxide dismutase and catalase. Moreover, C3G protected SH-SY5Y cells from oxidative stress. These results suggest that C3G decreased oxidative stress-induced cell injury by increasing the expression of Sirt1 and other antioxidant factors. Therefore, C3G might merit further investigation for use in attenuating the progress of neurodegenerative diseases.
Campdelacreu, J. (2014) Parkinson Disease and Alzheimer Disease: Environmental Risk Factors. Neurologia, 29, 541-549. https://doi.org/10.1016/j.nrl.2012.04.001
Sukprasansap, M., Chanvorachote, P. and Tencomnao, T. (2020) Cyanidin-3-Glucoside Activates Nrf2-Antioxidant Response Element and Protects against Glutamate-Induced Oxidative and Endoplasmic Reticulum Stress in HT22 Hippocampal Neuronal Cells. BMC Complementary Medicine and Therapies, 20, Article No. 46. https://doi.org/10.1186/s12906-020-2819-7
Tan, J., Li, Y., Hou, D.X. and Wu, S. (2019) The Effects and Mechanisms of Cyanidin-3-Glucoside and Its Phenolic Metabolites in Maintaining Intestinal Integrity. Antioxidants, 8, Article No. 479. https://doi.org/10.3390/antiox8100479
Chen, J., Sun, J., Jiang, J. and Zhou, J. (2018) Cyanidin Protects SH-SY5Y Human Neuroblastoma Cells from 1-Methyl-4-Phenylpyridinium-Induced Neurotoxicity. Pharmacology, 102, 126-132. https://doi.org/10.1159/000489853
Thummayot, S., Tocharus, C., Pinkaew, D., Viwatpinyo, K., Sringarm, K. and Tocharus, J. (2014) Neuroprotective Effect of Purple Rice Extract and Its Constituent Against Amyloid Beta-Induced Neuronal Cell Death in SK-N-SH Cells. Neurotoxicology, 45, 149-158. https://doi.org/10.1016/j.neuro.2014.10.010
Essa, M. M., Vijayan, R. K., Castellano-Gonzalez, G., Memon, M. A., Braidy, N. and Guillemin, G.J. (2012) Neuroprotective Effect of Natural Products against Alzheimer’s Disease. Neurochemical Research, 37, 1829-1842. https://doi.org/10.1007/s11064-012-0799-9
Tan, L., Yang, H.P., Pang, W., Lu, H., Hu, Y.D., Li, J., Lu, S.J., Zhang, W.Q. and Jiang, Y.G. (2014) Cyanidin-3-O-Galactoside and Blueberry Extracts Supplementation Improves Spatial Memory and Regulates Hippocampal ERK Expression in Senescence-Accelerated Mice. Biomedical and Environmental Sciences, 27, 186-196. https://doi.org/10.3967/bes2014.007
Imai, S., Armstrong, C.M., Kaeberlein, M. and Guarente, L. (2000) Transcriptional Silencing and Longevity Protein Sir2 Is an NAD-Dependent Histone Deacetylase. Nature, 403, 795-800. https://doi.org/10.1038/35001622
Chung, S., Yao, H., Caito, S., Hwang, J.W., Arunachalam, G. and Rahman, I. (2010) Regulation of SIRT1 in Cellular Functions: Role of Polyphenols. Archives of Biochemistry and Biophysics, 501, 79-90. https://doi.org/10.1016/j.abb.2010.05.003
Rahman, I., Kinnula, V.L., Gorbunova, V. and Yao, H. (2012) SIRT1 as a Therapeutic Target in Inflammaging of the Pulmonary Disease. Preventive Medicine, 54, S20-S28. https://doi.org/10.1016/j.ypmed.2011.11.014
Yao, H. and Rahman, I. (2012) Perspectives on Translational and Therapeutic Aspects of SIRT1 in Inflammaging and Senescence. Biochemical Pharmacology, 84, 1332-1339. https://doi.org/10.1016/j.bcp.2012.06.031
Yao, H., Chung, S., Hwang, J.W., Rajendrasozhan, S., Sundar, I.K., Dean, D.A., et al. (2012) SIRT1 Protects Against Emphysema via FOXO3-Mediated Reduction of Premature Senescence in Mice. Journal of Clinical Investigation, 122, 2032-2045. https://doi.org/10.1172/JCI60132
Singh, P., Hanson, P.S. and Morris, C.M. (2017) SIRT1 Ameliorates Oxidative Stress Induced Neural Cell Death and Is Down-Regulated in Parkinson’s Disease. BMC Neuroscience, 18, Article No. 46. https://doi.org/10.1186/s12868-017-0364-1
Lin, S.J., Defossez, P.A. and Guarente, L. (2000) Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae. Science, 289, 2126-2128. https://doi.org/10.1126/science.289.5487.2126
Dioum, E.M., Chen, R., Alexander, M.S., Zhang, Q., Hogg, R.T., Gerard, R.D., et al. (2009) Regulation of Hypoxia-Inducible Factor 2alpha Signaling by the Stress-Responsive Deacetylase Sirtuin 1. Science, 324, 1289-1293. https://doi.org/10.1126/science.1169956
Olmos, Y., Sánchez-Gómez, F.J., Wild, B., García-Quintans, N., Cabezudo, S., Lamas, S., et al. (2013) SirT1 Regulation of Antioxidant Genes Is Dependent on the Formation of a FoxO3a/PGC-1α Complex. Antioxidants and Redox Signaling, 19, 1507-1521. https://doi.org/10.1089/ars.2012.4713
Kume, S., Haneda, M., Kanasaki, K., Sugimoto, T., Araki, S., Isono, M., et al. (2006) Silent Information Regulator 2 (SIRT1) Attenuates Oxidative Stress-Induced Mesangial Cell Apoptosis via p53 Deacetylation. Free Radical Biology and Medicine, 40, 2175-2182. https://doi.org/10.1016/j.freeradbiomed.2006.02.014
Chua, K.F., Mostoslavsky, R., Lombard, D.B., Pang, W.W., Saito, S., Franco, S., et al. (2005) Mammalian SIRT1 Limits Replicative Life Span in Response to Chronic Genotoxic Stress. Cell Metabolism, 2, 67-76. https://doi.org/10.1016/j.cmet.2005.06.007
Magesh, S., Chen, Y. and Hu, L. (2012) Small Molecule Modulators of Keap1-Nrf2-ARE Pathway as Potential Preventive and Therapeutic Agents. Medicinal Research Reviews, 32, 687-726. https://doi.org/10.1002/med.21257
Kensler, T.W., Wakabayashi, N. and Biswal, S. (2007) Cell Survival Responses to Environmental Stresses via the Keap1-Nrf2-ARE Pathway. Annual Review of Pharmacology and Toxicology, 47, 89-116. https://doi.org/10.1146/annurev.pharmtox.46.120604.141046
Hayashi, A., Suzuki, H., Itoh, K., Yamamoto, M. and Sugiyama, Y. (2003) Transcription Factor Nrf2 Is Required for the Constitutive and Inducible Expression of Multidrug Resistance-Associated Protein 1 in Mouse Embryo Fibroblasts. Biochemical and Biophysical Research Communications, 310, 824-829. https://doi.org/10.1016/j.bbrc.2003.09.086
Kanzaki, H., Shinohara, F., Kajiya, M. and Kodama, T. (2013) The Keap1/Nrf2 Protein Axis Plays a Role in Osteoclast Differentiation by Regulating Intracellular Reactive Oxygen Species Signaling. Journal of Biological Chemistry, 288, 23009-23020. https://doi.org/10.1074/jbc.M113.478545
Dreger, H., Westphal, K., Weller, A., Baumann, G., Stangl, V., Meiners, S., et al. (2009) Nrf2-Dependent Upregulation of Antioxidative Enzymes: a Novel Pathway for Proteasome Inhibitor-Mediated Cardioprotection. Cardiovascular Research, 83, 354-361. https://doi.org/10.1093/cvr/cvp107
Parthasarathy, S., Barnett, J. and Fong, L.G. (1990) High-Density Lipoprotein Inhibits the Oxidative Modification of Low-Density Lipoprotein. Biochimica et Biophysica Acta, 1044, 275-283. https://doi.org/10.1016/0005-2760(90)90314-N
Hernandez-Baltazar, D., Zavala-Flores, L.M. and Villanueva-Olivo, A. (2017) The 6-Hydroxydopamine Model and Parkinsonian Pathophysiology: Novel Findings in an Older Model. Neurologia, 32, 533-539. https://doi.org/10.1016/j.nrl.2015.06.011
Terao, K. and Niki, E. (1986) Damage to Biological Tissues Induced by Radical Initiator 2,2’-Azobis(2-Amidinopropane) Dihydrochloride and Its Inhibition by Chain-Breaking Antioxidants. Journal of Free Radicals in Biology and Medicine, 2, 193-201. https://doi.org/10.1016/S0748-5514(86)80070-8
Hori, Y.S., Kuno, A., Hosoda, R. and Horio, Y. (2013) Regulation of FOXOs and p53 by SIRT1 Modulators under Oxidative Stress. PLoS ONE, 8, Article ID: e73875. https://doi.org/10.1371/journal.pone.0073875
Corpas, R., Revilla, S., Ursulet, S., Castro-Freire, M., Kaliman, P., Petegnief, V., et al. (2017) SIRT1 Overexpression in Mouse Hippocampus Induces Cognitive Enhancement through Proteostatic and Neurotrophic Mechanisms. Molecular Neurobiology, 54, 5604-5619. https://doi.org/10.1007/s12035-016-0087-9
Narasimhan, M., Patel, D., Vedpathak, D., Rathinam, M., Henderson, G. And Mahimainathan, L. (2012) Identification of Novel MicroRNAs in Post-Transcriptional Control of Nrf2 Expression and Redox Homeostasis in Neuronal, SH-SY5Y Cells. PLoS ONE, 7, Article ID: e51111. https://doi.org/10.1371/journal.pone.0051111
Zenkov, N.K., Menshchikova, E.B. and Tkachev, V.O. (2013 January) Keap1/Nrf2/ARE Redox-Sensitive Signaling System as a Pharmacological Target. Biochemistry. Biokhimiia, 78, 19-36. https://doi.org/10.1134/S0006297913010033
Chen, L., Li, K., Liu, Q., Quiles, J.L., Filosa, R., Kamal, M.A., et al. (2019) Protective Effects of Raspberry on the Oxidative Damage in HepG2 Cells through Keap1/Nrf2-Dependent Signaling Pathway. Food and Chemical Toxicology, 133, Article ID: 110781. https://doi.org/10.1016/j.fct.2019.110781
Kawai, Y., Garduño, L., Theodore, M., Yang, J. and Arinze, I.J. (2011) Acetylation-Deacetylation of the Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related factor 2) Regulates Its Transcriptional Activity and Nucleocytoplasmic Localization. Journal of Biological Chemistry, 286, 7629-7640. https://doi.org/10.1074/jbc.M110.208173
Kulkarni, S.R., Donepudi, A.C., Xu, J., Wei, W., Cheng, Q.C., Driscoll, M.V., et al. (2014) Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human. Antioxidants and Redox Signaling, 20, 15-30. https://doi.org/10.1089/ars.2012.5082
Mudò, G., Mäkelä, J., Di Liberto, V., Tselykh, T.V., Olivieri, M., Piepponen, P., et al. (2012) Transgenic Expression and Activation of PGC-1α Protect Dopaminergic Neurons in the MPTP Mouse Model of Parkinson’s Disease. Cellular and Molecular Life Sciences, 69, 1153-1165. https://doi.org/10.1007/s00018-011-0850-z
Tarozzi, A., Morroni, F., Merlicco, A., Bolondi, C., Teti, G., Falconi, M., et al. (2010) Neuroprotective Effects of Cyanidin 3-O-Glucopyranoside on Amyloid Beta (25-35) Oligomer-Induced Toxicity. Neuroscience Letters, 473, 72-76. https://doi.org/10.1016/j.neulet.2010.02.006
Vincent, A.M., Kato, K., McLean, L.L., Soules, M.E. and Feldman, E.L. (2009) Sensory Neurons and Schwann Cells Respond to Oxidative Stress by Increasing Antioxidant Defense Mechanisms. Antioxidants and Redox Signaling, 11, 425-438. https://doi.org/10.1089/ars.2008.2235
Kim, H.J. and Vaziri, N.D. (2010) Contribution of Impaired Nrf2-Keap1 Pathway to Oxidative Stress and Inflammation in Chronic Renal Failure. American Journal of Physiology. Renal Physiology, 298, F662-F671. https://doi.org/10.1152/ajprenal.00421.2009
Okita, Y., Kamoshida, A., Suzuki, H., Itoh, K., Motohashi, H., Igarashi, K., et al. (2013) Transforming Growth Factor-β Induces Transcription Factors MafK and Bach1 to Suppress Expression of the Heme Oxygenase-1 Gene. Journal of Biological Chemistry, 288, 20658-20667. https://doi.org/10.1074/jbc.M113.450478
Kim, G.H., Kim, J.E., Rhie, S.J. and Yoon, S. (2015) The Role of Oxidative Stress in Neurodegenerative Diseases. Experimental Neurobiology, 24, 325-340. https://doi.org/10.5607/en.2015.24.4.325