Planta Med 2018; 84(01): 34-41
DOI: 10.1055/s-0043-114865
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Epigallocatechin-3-Gallate Protects against Homocysteine-Induced Brain Damage in Rats

Lili Wang
The Second Department of Neurology, Cangzhou City Peopleʼs Hospital, Cangzhou, China
,
Xuan Tian
The Second Department of Neurology, Cangzhou City Peopleʼs Hospital, Cangzhou, China
› Author Affiliations
Further Information

Publication History

received 28 March 2017
revised 08 June 2017

accepted 18 June 2017

Publication Date:
30 June 2017 (online)

Abstract

High levels of homocysteine are implicated in many neurovascular and neurodegeneration diseases. Epigallocatechin 3-gallate (EGCG), one of green tea polyphenols, has potential anti-oxidative and anti-inflammatory activities. However, it has not been explored whether EGCG has an effect on homocysteine-induced neuro-inflammation and neurodegeneration. In this study, we investigated the effects of EGCG on memory deficit, oxidative stress, neuro-inflammation, and neurodegeneration in hyper-homocysteinemic rats after a 2 wk homocysteine injection by vena caudalis. We found that supplementation of EGCG could rescue deficit of spatial memory induced by homocysteine. Treatment of EGCG significantly reduced the expression of malondialdehyde, glial fibrillary acidic protein, tumor necrosis factor-α, and interleukin-1β and increased glutathione level in the homocysteine-treated group. In TdT-mediated dUTP nick end labeling (TUNEL) assay and Fluoro-Jade B staining, supplementation of EGCG could attenuate the apoptotic neurons and neurodegeneration. Interestingly, EGCG significantly ameliorated homocysteine-induced cerebrovascular injury. Our data suggest that EGCG could be a promising candidate for arresting homocysteine-induced neurodegeneration and neuro-inflammation in the brain.

 
  • References

  • 1 Medina M, Urdiales JL, Amores-Sanchez MI. Roles of homocysteine in cell metabolism: old and new functions. Eur J Biochem 2001; 268: 3871-3882
  • 2 Sachdev PS. Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 1152-1161
  • 3 Pasini FL, Frigerio C, Petri S, Di Perri T. Plasma homocysteine in ischemic stroke. Stroke 1995; 26: 2374-2375
  • 4 Houston PE, Rana S, Sekhsaria S, Perlin E, Kim KS, Castro OL. Homocysteine in sickle cell disease: relationship to stroke. Am J Med 1997; 103: 192-196
  • 5 Perry IJ. Homocysteine and risk of stroke. J Cardiovasc Risk 1999; 6: 235-240
  • 6 Williams WM, Chung YW. Evidence for an age-related attenuation of cerebral microvascular antioxidant response to oxidative stress. Life Sci 2006; 79: 1638-1644
  • 7 McIlroy SP, Dynan KB, Lawson JT, Patterson CC, Passmore AP. Moderately elevated plasma homocysteine, methylenetetrahydrofolate reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland. Stroke 2002; 33: 2351-2356
  • 8 Banecka-Majkutewicz Z, Sawula W, Kadzinski L, Wegrzyn A, Banecki B. Homocysteine, heat shock proteins, genistein and vitamins in ischemic stroke – pathogenic and therapeutic implications. Acta Biochim Pol 2012; 59: 495-499
  • 9 Spence JD. Homocysteine lowering for stroke prevention: unravelling the complexity of the evidence. Int J Stroke 2016; 11: 744-747
  • 10 Perna AF, Ingrosso D, De Santo NG. Homocysteine and oxidative stress. Amino Acids 2003; 25: 409-417
  • 11 Yan SK, Chang T, Wang H, Wu L, Wang R, Meng QH. Effects of hydrogen sulfide on homocysteine-induced oxidative stress in vascular smooth muscle cells. Biochem Biophys Res Commun 2006; 351: 485-491
  • 12 Sawle P, Foresti R, Green CJ, Motterlini R. Homocysteine attenuates endothelial haem oxygenase-1 induction by nitric oxide (NO) and hypoxia. FEBS Lett 2001; 508: 403-406
  • 13 Fu WY, Dudman NP, Perry MA, Wang XL. Homocysteine attenuates hemodynamic responses to nitric oxide in vivo . Atherosclerosis 2002; 161: 169-176
  • 14 Mangiagalli A, Samuele A, Armentero MT, Bazzini E, Nappi G, Blandini F. Effects of homocysteine on apoptosis-related proteins and anti-oxidant systems in isolated human lymphocytes. Eur J Biochem 2004; 271: 1671-1676
  • 15 Choi JW, Lee MH, Fujii T, Fujii N, Moon Y. Association of the urine homocysteine creatinine ratio to proinflammatory cytokine, netural anticoagulant and NO levels in cerebrovascular disease. Ann Clin Lab Sci 2014; 44: 461-465
  • 16 Chern CL, Huang RF, Chen YH, Cheng JT, Liu TZ. Folate deficiency-induced oxidative stress and apoptosis are mediated via homocysteine-dependent overproduction of hydrogen peroxide and enhanced activation of NF-kappaB in human Hep G2 cells. Biomed Pharmacother 2001; 55: 434-442
  • 17 Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, Mattson MP. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 2000; 20: 6920-6926
  • 18 Outinen PA, Sood SK, Liaw PC, Sarge KD, Maeda N, Hirsh J, Ribau J, Podor TJ, Weitz JI, Austin RC. Characterization of the stress-inducing effects of homocysteine. Biochem J 1998; 332 (Pt 1): 213-221
  • 19 Kamat PK, Kalani A, Givvimani S, Sathnur PB, Tyagi SC, Tyagi N. Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice. Neuroscience 2013; 252: 302-319
  • 20 Singh NA, Mandal AK, Khan ZA. Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr J 2016; 15: 60
  • 21 Zhang BK, Lai YQ, Niu PP, Zhao M, Jia SJ. Epigallocatechin-3-gallate inhibits homocysteine-induced apoptosis of endothelial cells by demethylation of the DDAH2 gene. Planta Med 2013; 79: 1715-1719
  • 22 Ye Q, Ye L, Xu X, Huang B, Zhang X, Zhu Y, Chen X. Epigallocatechin-3-gallate suppresses 1-methyl-4-phenyl-pyridine-induced oxidative stress in PC12 cells via the SIRT1/PGC-1alpha signaling pathway. BMC Complement Altern Med 2012; 12: 82
  • 23 Abib RT, Peres KC, Barbosa AM, Peres TV, Bernardes A, Zimmermann LM, Quincozes-Santos A, Fiedler HD, Leal RB, Farina M, Gottfried C. Epigallocatechin-3-gallate protects rat brain mitochondria against cadmium-induced damage. Food Chem Toxicol 2011; 49: 2618-2623
  • 24 Devika PT, Stanely Mainzen Prince P. Protective effect of (−)-epigallocatechin-gallate (EGCG) on lipid peroxide metabolism in isoproterenol induced myocardial infarction in male Wistar rats: a histopathological study. Biomed Pharmacother 2008; 62: 701-708
  • 25 Yeoh BS, Aguilera Olvera R, Singh V, Xiao X, Kennett MJ, Joe B, Lambert JD, Vijay-Kumar M. Epigallocatechin-3-gallate inhibition of myeloperoxidase and its counter-regulation by dietary iron and lipocalin 2 in murine model of gut inflammation. Am J Pathol 2016; 186: 912-926
  • 26 Zhang CE, Wei W, Liu YH, Peng JH, Tian Q, Liu GP, Zhang Y, Wang JZ. Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. Am J Pathol 2009; 174: 1481-1491
  • 27 Soung H, Wang M, Tseng H, Fang H, Chang K. (−)Epigallocatechin-3-gallate decreases the stress-induced impairment of learning and memory in rats. Neurosci Lett 2015; 602: 27-32
  • 28 Gibbons T, Pence B, Petr G, Ossyra J, Mach H, Bhattacharya T, Perez S, Martin S, McCusker R, Kelley K, Rhodes J, Johnson R, Woods J. Voluntary wheel running, but not a diet containing (−)-epigallocatechin-3-gallate and β-alanine, improves learning, memory and hippocampal neurogenesis in aged mice. Behav Brain Res 2014; 272: 131-140
  • 29 Han S, Wu H, Li W, Gao P. Protective effects of genistein in homocysteine-induced endothelial cell inflammatory injury. Mol Cell Biochem 2015; 403: 43-49
  • 30 DʼErasmo E, Acca M, Pisani D, Volpe MS. Neurological state, infarct size and clinical outcome are related to early platelet count decrease in stroke. Gerontology 1993; 39: 276-279
  • 31 Lominadze D, Joshua IG, Schuschke DA. Increased erythrocyte aggregation in spontaneously hypertensive rats. Am J Hypertens 1998; 11: 784-789
  • 32 Dona M, DellʼAica I, Calabrese F, Benelli R, Morini M, Albini A, Garbisa S. Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis. J Immunol 2003; 170: 4335-4341
  • 33 Wang J, Bai X, Chen Y, Zhao Y, Liu X. Homocysteine induces apoptosis of rat hippocampal neurons by inhibiting 14-3-3epsilon expression and activating calcineurin. PLoS One 2012; 7: e48247
  • 34 Ataie A, Ataee R, Mansoury Z, Aghajanpour M. Homocysteine intracerebroventricular injection induces apoptosis in the substantia nigra cells and Parkinsonʼs disease like behavior in rats. Int J Mol Cell Med 2013; 2: 80-85
  • 35 Lehotsky J, Petras M, Kovalska M, Tothova B, Drgova A, Kaplan P. Mechanisms involved in the ischemic tolerance in brain: effect of the homocysteine. Cell Mol Neurobiol 2015; 35: 7-15
  • 36 Mandel S, Weinreb O, Amit T, Youdim MB. Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (−)-epigallocatechin-3-gallate: implications for neurodegenerative diseases. J Neurochem 2004; 88: 1555-1569
  • 37 Chai GS, Jiang X, Ni ZF, Ma ZW, Xie AJ, Cheng XS, Wang Q, Wang JZ, Liu GP. Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine. J Neurochem 2013; 124: 388-396