Cyanidin is an anthocyanidin extracted from a variety of fruits and vegetables. Cyanidin showed benefits against diabetes, cancer, and atherosclerosis. However, the potential neuroprotective effects of cyanidin against Parkinson’s disease (PD) have not been examined. Indicated concentrations of cyanidin (1, 3, 10, and 30 μmol/L) were incubated together with 0.5 mmol/L 1-methyl-4-phenylpyridinium (MPP+) to human neuroblastoma SH-SY5Y cells. We found cyanidin prevented MPP+-induced cell demise in a concentration-dependent manner. Cyanidin significantly reduced MPP+-induced apoptosis, this is reflected by decreased TdT-mediated dUTP nick-end labeling staining and caspase-3 expressions. Further, MPP+ increased the Bax/Bcl-2 ratio, which was partly reversed by cyanidin. We also found cyanidin attenuated the MPP+-induced mitochondrial oxidative stress as revealed by decreased MitoSOX staining. Taken together, these data for the first time indicated the -neuroprotective effects of cyanidin against MPP+-induced -SH-SY5Y cell death. These findings shed light on the potential implications of cyanidin for PD treatment.

Keywords:
Cyanidin, 1-methyl-4-phenylpyridinium, Parkinson’s disease, SH-SY5Y, Neuroprotective effects
1.
Hammond C, Bergman H, Brown P: Pathological synchronization in Parkinson’s disease: networks, models and treatments. Trends Neurosci 2007; 30: 357–364.
2.
Savitt JM, Dawson VL, Dawson TM: Diagnosis and treatment of Parkinson’s disease: molecules to medicine. J Clin Invest 2006; 116: 1744–1754.
3.
Espin JC, Soler-Rivas C, Wichers HJ, Garcia-Viguera C: Anthocyanin-based natural colorants: a new source of antiradical activity for foodstuff. J Agric Food Chem 2000; 48: 1588–1592.
4.
Sasaki R, Nishimura N, Hoshino H, Isa Y, Kadowaki M, Ichi T, et al: Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. Biochem Pharmacol 2007; 74: 1619–1627.
5.
Lee JS, Kim YR, Park JM, Kim YE, Baek NI, Hong EK: Cyanidin-3-glucoside isolated from mulberry fruits protects pancreatic β-cells against glucotoxicity-induced apoptosis. Mol Med Rep 2015; 11: 2723–2728.
6.
Chen PN, Chu SC, Chiou HL, Kuo WH, Chiang CL, Hsieh YS: Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett 2006; 235: 248–259.
7.
Cvorovic J, Tramer F, Granzotto M, Candussio L, Decorti G, Passamonti S: Oxidative stress-based cytotoxicity of delphinidin and cyanidin in colon cancer cells. Arch Biochem Biophys 2010; 501: 151–157.
8.
Li X, Xu J, Tang X, Liu Y, Yu X, Wang Z, et al: Anthocyanins inhibit trastuzumab-resistant breast cancer in vitro and in vivo. Mol Med Rep 2016; 13: 4007–4013.
9.
Oak MH, Bedoui JE, Madeira SV, Chalupsky K, Schini-Kerth VB: Delphinidin and cyanidin inhibit PDGF(AB)-induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK. Br J Pharmacol 2006; 149: 283–290.
10.
Qin L, Zhang J, Qin M: Protective effect of cyanidin 3-o-glucoside on beta-amyloid peptide-induced cognitive impairment in rats. Neurosci Lett 2013; 534: 285–288.
11.
Carvalho FB, Gutierres JM, Bohnert C, Zago AM, Abdalla FH, Vieira JM, et al: Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination. J Nutr Biochem 2015; 26: 378–390.
12.
Xie HR, Hu LS, Li GY: SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson’s disease. Chin Med J (Engl) 2010; 123: 1086–1092.
13.
Oh Y, Jeong K, Kim K, Lee YS, Jeong S, Kim SS, et al: Cyclophilin B protects SH-SY5Y human neuroblastoma cells against MPP(+)-induced neurotoxicity via JNK pathway. Biochem Biophys Res Commun 2016; 478: 1396–1402.
14.
Wang XJ, Xu JX: Salvianic acid A protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity. Neurosci Res 2005; 51: 129–138.
15.
Dauer W, Przedborski S: Parkinson’s disease: mechanisms and models. Neuron 2003; 39: 889–909.
16.
Ebrahimi A, Schluesener H: Natural polyphenols against neurodegenerative disorders: potentials and pitfalls. Ageing Res Rev 2012; 11: 329–345.
17.
Mochizuki H, Goto K, Mori H, Mizuno Y: Histochemical detection of apoptosis in Parkinson’s disease. J Neurol Sci 1996; 137: 120–123.
18.
Fall CP, Bennett JP Jr: Characterization and time course of MPP+ -induced apoptosis in human SH-SY5Y neuroblastoma cells. J Neurosci Res 1999; 55: 620–628.
19.
Abou-Sleiman PM, Muqit MM, Wood NW: Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nat Rev Neurosci 2006; 7: 207–219.
20.
Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, et al: Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 1999; 397: 441–446.
21.
Brunelle JK, Letai A: Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci 2009; 122: 437–441.
22.
Feng R, Ni HM, Wang SY, Tourkova IL, Shurin MR, Harada H, et al: Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. J Biol Chem 2007; 282: 13468–13476.
23.
Noda Y, Kaneyuki T, Mori A, Packer L: Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyanidin, and pelargonidin. J Agric Food Chem 2002; 50: 166–171.
24.
Cassarino DS, Parks JK, Parker WD Jr, Bennett JP Jr: The Parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism. Biochim Biophys Acta 1999; 1453: 49–62.
25.
Ott M, Gogvadze V, Orrenius S, Zhivotovsky B: Mitochondria, oxidative stress and cell death. Apoptosis 2007; 12: 913–922.
26.
Mukhopadhyay P, Rajesh M, Yoshihiro K, Hasko G, Pacher P: Simple quantitative detection of mitochondrial superoxide production in live cells. Biochem Biophys Res Commun 2007; 358: 203–208.
27.
Gan L, Johnson JA: Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim Biophys Acta 2017; 1842: 1208–1218.
28.
Shukitt-Hale B, Lau FC, Joseph JA: Berry fruit supplementation and the aging brain. J Agric Food Chem 2008; 56: 636–641.
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2018
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