Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Protective effects of Populus tomentiglandulosa against cognitive impairment by regulating oxidative stress in an amyloid beta25-35-induced Alzheimer's disease mouse model

  • Kwon, Yu Ri (Department of Food Science and Nutrition, Pusan National University) ;
  • Kim, Ji-Hyun (Department of Food Science and Nutrition, Pusan National University) ;
  • Lee, Sanghyun (Department of Plant Science and Technology, Chung-Ang University) ;
  • Kim, Hyun Young (Department of Food Science, Gyeongsang National University) ;
  • Cho, Eun Ju (Department of Food Science and Nutrition, Pusan National University)
  • Received : 2021.03.24
  • Accepted : 2021.06.29
  • Published : 2022.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ). Several studies on the antioxidant activity and protective effects of Populus tomentiglandulosa (PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD. MATERIALS/METHODS: We orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ25-35-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues. RESULTS: PT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity. Furthermore, administration of PT significantly inhibited the production of lipid peroxide, NO, and ROS in the brain, liver, and kidney, suggesting that PT protected against oxidative stress. CONCLUSIONS: Our study demonstrated that administration of PT improved Aβ25-35-induced cognitive impairment by regulating oxidative stress. Therefore, we propose that PT could be used as a natural agent for AD improvement.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2019R1F1A1054676).

References

  1. Jahn H. Memory loss in Alzheimer's disease. Dialogues Clin Neurosci 2013;15:445-54. https://doi.org/10.31887/DCNS.2013.15.4/hjahn
  2. Derby CA. Trends in the public health significance, definitions of disease, and implications for prevention of Alzheimer's disease. Curr Epidemiol Rep 2020;7:68-76. https://doi.org/10.1007/s40471-020-00231-8
  3. Zhao N, Ren Y, Yamazaki Y, Qiao W, Li F, Felton LM, Mahmoudiandehkordi S, Kueider-Paisley A, Sonoustoun B, Arnold M, et al. Alzheimer's Risk Factors Age, APOE Genotype, and Sex Drive Distinct Molecular Pathways. Neuron 2020;106:727-742.e6. https://doi.org/10.1016/j.neuron.2020.02.034
  4. Oudin A. Short review: air pollution, noise and lack of greenness as risk factors for Alzheimer's disease- epidemiologic and experimental evidence. Neurochem Int 2020;134:104646. https://doi.org/10.1016/j.neuint.2019.104646
  5. Gotz J, Streffer JR, David D, Schild A, Hoerndli F, Pennanen L, Kurosinski P, Chen F. Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy. Mol Psychiatry 2004;9:664-83. https://doi.org/10.1038/sj.mp.4001508
  6. Jakob-Roetne R, Jacobsen H. Alzheimer's disease: from pathology to therapeutic approaches. Angew Chem Int Ed Engl 2009;48:3030-59. https://doi.org/10.1002/anie.200802808
  7. Dhitavat S, Rivera ER, Rogers E, Shea TB. Differential efficacy of lipophilic and cytosolic antioxidants on generation of reactive oxygen species by amyloid-β. J Alzheimers Dis 2001;3:525-9. https://doi.org/10.3233/JAD-2001-3602
  8. De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, Klein WL. Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 2007;282:11590-601. https://doi.org/10.1074/jbc.M607483200
  9. Loh KP, Huang SH, De Silva R, Tan BK, Zhu YZ. Oxidative stress: apoptosis in neuronal injury. Curr Alzheimer Res 2006;3:327-37. https://doi.org/10.2174/156720506778249515
  10. Takuma K, Baba A, Matsuda T. Astrocyte apoptosis: implications for neuroprotection. Prog Neurobiol 2004;72:111-27. https://doi.org/10.1016/j.pneurobio.2004.02.001
  11. Ellis JM. Cholinesterase inhibitors in the treatment of dementia. J Am Osteopath Assoc 2005;105:145-58.
  12. Kwak JH, Oh YS. Evaluation of Populus alba × glandulosa as raw material of particleboard. J Korean For Soc 2003;92:140-4.
  13. Choi SI, Hwang SJ, Lee OH, Kim JD. Antioxidant activity and component analysis of Populus tomentiglandulosa extract. Korean J Food Sci Technol 2020;52:119-24.
  14. Dudonne S, Poupard P, Coutiere P, Woillez M, Richard T, Merillon JM, Vitrac X. Phenolic composition and antioxidant properties of poplar bud (Populus nigra) extract: individual antioxidant contribution of phenolics and transcriptional effect on skin aging. J Agric Food Chem 2011;59:4527-36. https://doi.org/10.1021/jf104791t
  15. Lee HJ, Kim JS, Kim YK, Ryu JH. Phenolic glycosides as inhibitors of inducible nitric oxide synthase from Populus davidiana in LPS-activated RAW 264.7 murine macrophages. Pharmazie 2012;67:870-3.
  16. Debbache-Benaida N, Atmani-Kilani D, Schini-Keirth VB, Djebbli N, Atmani D. Pharmacological potential of Populus nigra extract as antioxidant, anti-inflammatory, cardiovascular and hepatoprotective agent. Asian Pac J Trop Biomed 2013;3:697-704. https://doi.org/10.1016/S2221-1691(13)60141-0
  17. Lee CH, Park JH, Ahn JH, Kim JD, Cho JH, Lee TK, Won MH. Stronger antioxidant enzyme immunoreactivity of Populus tomentiglandulosa extract than ascorbic acid in rat liver and kidney. Iran J Basic Med Sci 2019;22:963-7.
  18. Park JH, Lee TK, Ahn JH, Shin BN, Cho JH, Kim IH, Lee JC, Kim JD, Lee YJ, Kang IJ, et al. Pre-treated Populus tomentiglandulosa extract inhibits neuronal loss and alleviates gliosis in the gerbil hippocampal CA1 area induced by transient global cerebral ischemia. Anat Cell Biol 2017;50:284-92. https://doi.org/10.5115/acb.2017.50.4.284
  19. Glascock JJ, Osman EY, Coady TH, Rose FF, Shababi M, Lorson CL. Delivery of therapeutic agents through intracerebroventricular (ICV) and intravenous (IV) injection in mice. J Vis Exp 2011;56:2968.
  20. Kim JH, He MT, Kim MJ, Yang CY, Shin YS, Yokozawa T, Park CH, Cho EJ. Safflower (Carthamus tinctorius L.) seed attenuates memory impairment induced by scopolamine in mice via regulation of cholinergic dysfunction and oxidative stress. Food Funct 2019;10:3650-9. https://doi.org/10.1039/C9FO00615J
  21. Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study 'recognition memory'. Nat Protoc 2006;1:1306-11. https://doi.org/10.1038/nprot.2006.205
  22. He MT, Lee AY, Kim JH, Park CH, Shin YS, Cho EJ. Protective role of Cordyceps militaris in Aβ1-42-induced Alzheimer's disease in vivo. Food Sci Biotechnol 2018;28:865-72. https://doi.org/10.1007/s10068-018-0521-z
  23. Jang WS, Choung SY. Antiobesity effects of the ethanol extract of Laminaria japonica Areshoung in high-fat-diet-induced obese rat. Evid Based Complement Alternat Med 2013;2013:492807.
  24. Kim JH, Lee J, Lee S, Cho EJ. Quercetin and quercetin-3-β-D-glucoside improve cognitive and memory function in Alzheimer's disease mouse. Appl Biol Chem 2016;59:721-8. https://doi.org/10.1007/s13765-016-0217-0
  25. Lee AY, Choi JM, Lee J, Lee MH, Lee S, Cho EJ. Effects of vegetable oils with different fatty acid compositions on cognition and memory ability in Aβ25-35-induced Alzheimer's disease mouse model. J Med Food 2016;19:912-21. https://doi.org/10.1089/jmf.2016.3737
  26. Park CH, Lee AY, Kim JH, Seong SH, Cho EJ, Choi JS, Kim MJ, Yang S, Yokozawa T, Shin YS. Protective effects of serotonin and its derivatives, N-feruloylserotonin and N-(p-coumaroyl) serotonin, against cisplatin-induced renal damage in mice. Am J Chin Med 2019;47:369-83. https://doi.org/10.1142/s0192415x19500186
  27. Chauhan V, Chauhan A. Oxidative stress in Alzheimer's disease. Pathophysiology 2006;13:195-208. https://doi.org/10.1016/j.pathophys.2006.05.004
  28. Ovchinnikova OY, Finder VH, Vodopivec I, Nitsch RM, Glockshuber R. The Osaka FAD mutation E22Δ leads to the formation of a previously unknown type of amyloid β fibrils and modulates Aβ neurotoxicity. J Mol Biol 2011;408:780-91. https://doi.org/10.1016/j.jmb.2011.02.049
  29. Canevari L, Abramov AY, Duchen MR. Toxicity of amyloid β peptide: tales of calcium, mitochondria, and oxidative stress. Neurochem Res 2004;29:637-50. https://doi.org/10.1023/b:nere.0000014834.06405.af
  30. Agostinho P, Cunha RA, Oliveira C. Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease. Curr Pharm Des 2010;16:2766-78. https://doi.org/10.2174/138161210793176572
  31. Tarus B, Nguyen PH, Berthoumieu O, Faller P, Doig AJ, Derreumaux P. Molecular structure of the NQTrp inhibitor with the Alzheimer Aβ1-28 monomer. Eur J Med Chem 2015;91:43-50. https://doi.org/10.1016/j.ejmech.2014.07.002
  32. Lee YW, Kim DH, Jeon SJ, Park SJ, Kim JM, Jung JM, Lee HE, Bae SG, Oh HK, Son KH, et al. Neuroprotective effects of salvianolic acid B on an Aβ25-35 peptide-induced mouse model of Alzheimer's disease. Eur J Pharmacol 2013;704:70-7. https://doi.org/10.1016/j.ejphar.2013.02.015
  33. Liu RT, Zou LB, Lu QJ. Liquiritigenin inhibits Abeta(25-35)-induced neurotoxicity and secretion of Abeta(1-40) in rat hippocampal neurons. Acta Pharmacol Sin 2009;30:899-906. https://doi.org/10.1038/aps.2009.74
  34. Liu YM, Li ZY, Hu H, Xu SP, Chang Q, Liao YH, Pan RL, Liu XM. Tenuifolin, a secondary saponin from hydrolysates of polygalasaponins, counteracts the neurotoxicity induced by Aβ25-35 peptides in vitro and in vivo. Pharmacol Biochem Behav 2015;128:14-22. https://doi.org/10.1016/j.pbb.2014.11.010
  35. Mabunga DF, Park D, Ryu O, Valencia ST, Adil KJ, Kim S, Kwon KJ, Shin CY, Jeon SJ. Recapitulation of neuropsychiatric behavioral features in mice using acute low-dose MK-801 administration. Exp Neurobiol 2019;28:697-708. https://doi.org/10.5607/en.2019.28.6.697
  36. Hsieh LS, Wen JH, Miyares L, Lombroso PJ, Bordey A. Outbred CD1 mice are as suitable as inbred C57BL/6J mice in performing social tasks. Neurosci Lett 2017;637:142-7. https://doi.org/10.1016/j.neulet.2016.11.035
  37. Lee AY, Choi JM, Lee YA, Shin SH, Cho EJ. Beneficial effect of black rice (Oryza sativa L. var. japonica) extract on amyloid β-induced cognitive dysfunction in a mouse model. Exp Ther Med 2020;20:64.
  38. Cho CH, Jung YS, Kim JM, Nam TG, Lee SH, Cho HS, Song MC, Heo HJ, Kim DO. Neuroprotective effects of Actinidia eriantha cv. Bidan kiwifruit on amyloid beta-induced neuronal damages in PC-12 cells and ICR mice. J Funct Foods 2021;79:104398. https://doi.org/10.1016/j.jff.2021.104398
  39. Cacabelos R. Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics. Neuropsychiatr Dis Treat 2007;3:303-33.
  40. Dooley M, Lamb HM. Donepezil: a review of its use in Alzheimer's disease. Drugs Aging 2000;16:199-226. https://doi.org/10.2165/00002512-200016030-00005
  41. Mehta M, Adem A, Sabbagh M. New acetylcholinesterase inhibitors for Alzheimer's disease. Int J Alzheimers Dis 2012;2012:728983.
  42. Umukoro S, Adewole FA, Eduviere AT, Aderibigbe AO, Onwuchekwa C. Free radical scavenging effect of donepezil as the possible contribution to its memory enhancing activity in mice. Drug Res (Stuttg) 2014;64:236-9. https://doi.org/10.1055/s-0033-1357126
  43. Kim HG, Moon M, Choi JG, Park G, Kim AJ, Hur J, Lee KT, Oh MS. Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo. Neurotoxicology 2014;40:23-32. https://doi.org/10.1016/j.neuro.2013.10.004
  44. Choi SI, Hwang SJ, Lee OH, Kim JD. Antioxidant activity and component analysis of Populus tomentiglandulosa extract. Korean J Food Sci Technol 2020;52:119-24.
  45. He J, Xu L, Yang L, Wang X. Epigallocatechin gallate is the most effective catechin against antioxidant stress via hydrogen peroxide and radical scavenging activity. Med Sci Monit 2018;24:8198-206. https://doi.org/10.12659/msm.911175
  46. Lim HJ, Shim SB, Jee SW, Lee SH, Lim CJ, Hong JT, Sheen YY, Hwang DY. Green tea catechin leads to global improvement among Alzheimer's disease-related phenotypes in NSE/hAPP-C105 Tg mice. J Nutr Biochem 2013;24:1302-13. https://doi.org/10.1016/j.jnutbio.2012.10.005
  47. Wenk GL. Assessment of spatial memory using the T maze. Curr Protoc Neurosci 1998;4:8.5B.1.
  48. McHugh SB, Niewoehner B, Rawlins JN, Bannerman DM. Dorsal hippocampal N-methyl-D-aspartate receptors underlie spatial working memory performance during non-matching to place testing on the T-maze. Behav Brain Res 2008;186:41-7. https://doi.org/10.1016/j.bbr.2007.07.021
  49. Choi YY, Maeda T, Fujii H, Yokozawa T, Kim HY, Cho EJ, Shibamoto T. Oligonol improves memory and cognition under an amyloid β(25-35)-induced Alzheimer's mouse model. Nutr Res 2014;34:595-603. https://doi.org/10.1016/j.nutres.2014.06.008
  50. Farr SA, Roesler E, Niehoff ML, Roby DA, McKee A, Morley JE. Metformin improves learning and memory in the SAMP8 mouse model of Alzheimer's disease. J Alzheimers Dis 2019;68:1699-710. https://doi.org/10.3233/JAD-181240
  51. Deacon RM, Rawlins JN. T-maze alternation in the rodent. Nat Protoc 2006;1:7-12. https://doi.org/10.1038/nprot.2006.2
  52. Lee AY, Hwang BR, Lee MH, Lee S, Cho EJ. Perilla frutescens var. japonica and rosmarinic acid improve amyloid-β25-35 induced impairment of cognition and memory function. Nutr Res Pract 2016;10:274-81. https://doi.org/10.4162/nrp.2016.10.3.274
  53. Denninger JK, Smith BM, Kirby ED. Novel object recognition and object location behavioral testing in mice on a budget. J Vis Exp 2018:e58593.
  54. Bengoetxea X, Rodriguez-Perdigon M, Ramirez MJ. Object recognition test for studying cognitive impairments in animal models of Alzheimer's disease. Front Biosci (Schol Ed) 2015;7:10-29. https://doi.org/10.2741/421
  55. Lueptow LM. Novel object recognition test for the investigation of learning and memory in mice. J Vis Exp 2017:e55718.
  56. Lu P, Mamiya T, Lu L, Mouri A, Ikejima T, Kim HC, Zou LB, Nabeshima T. Xanthoceraside attenuates amyloid β peptide25-35-induced learning and memory impairments in mice. Psychopharmacology (Berl) 2012;219:181-90. https://doi.org/10.1007/s00213-011-2386-1
  57. Bromley-Brits K, Deng Y, Song W. Morris water maze test for learning and memory deficits in Alzheimer's disease model mice. J Vis Exp 2011;53:e2920.
  58. Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 2006;1:848-58. https://doi.org/10.1038/nprot.2006.116
  59. Tian H, Ding N, Guo M, Wang S, Wang Z, Liu H, Yang J, Li Y, Ren J, Jiang J, et al. Analysis of learning and memory ability in an Alzheimer's disease mouse model using the Morris water maze. J Vis Exp 2019:e60055.
  60. Nino SA, Morales-Martinez A, Chi-Ahumada E, Carrizales L, Salgado-Delgado R, Perez-Severiano F, Diaz-Cintra S, Jimenez-Capdeville ME, Zarazua S. Arsenic exposure contributes to the bioenergetic damage in an Alzheimer's disease model. ACS Chem Neurosci 2019;10:323-36. https://doi.org/10.1021/acschemneuro.8b00278
  61. Kwon SH, Lee HK, Kim JA, Hong SI, Kim SY, Jo TH, Park YI, Lee CK, Kim YB, Lee SY, et al. Neuroprotective effects of Eucommia ulmoides Oliv. Bark on amyloid beta(25-35)-induced learning and memory impairments in mice. Neurosci Lett 2011;487:123-7. https://doi.org/10.1016/j.neulet.2010.10.042
  62. Huang XJ, Choi YK, Im HS, Yarimaga O, Yoon E, Kim HS. Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors (Basel) 2006;6:756-82. https://doi.org/10.3390/s6070756
  63. Lee TK, Park JH, Ahn JH, Kim H, Song M, Lee JC, Kim JD, Jeon YH, Choi JH, Lee CH, et al. Pretreatment of Populus tomentiglandulosa protects hippocampal CA1 pyramidal neurons from ischemia-reperfusion injury in gerbils via increasing SODs expressions and maintaining BDNF and IGF-I expressions. Chin J Nat Med 2019;17:424-34.
  64. Park JH, Lee TK, Ahn JH, Shin BN, Cho JH, Kim IH, Lee JC, Kim JD, Lee YJ, Kang IJ, et al. Pre-treated Populus tomentiglandulosa extract inhibits neuronal loss and alleviates gliosis in the gerbil hippocampal CA1 area induced by transient global cerebral ischemia. Anat Cell Biol 2017;50:284-92. https://doi.org/10.5115/acb.2017.50.4.284
  65. Lee CH, Park JH, Ahn JH, Kim JD, Cho JH, Lee TK, Won MH. Stronger antioxidant enzyme immunoreactivity of Populus tomentiglandulosa extract than ascorbic acid in rat liver and kidney. Iran J Basic Med Sci 2019;22:963-7.
  66. Rajmohan R, Reddy PH. Amyloid-Beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer's disease neurons. J Alzheimers Dis 2017;57:975-99. https://doi.org/10.3233/JAD-160612
  67. Wang D, Noda Y, Zhou Y, Mouri A, Mizoguchi H, Nitta A, Chen W, Nabeshima T. The allosteric potentiation of nicotinic acetylcholine receptors by galantamine ameliorates the cognitive dysfunction in beta amyloid25-35 i.c.v.-injected mice: involvement of dopaminergic systems. Neuropsychopharmacology 2007;32:1261-71. https://doi.org/10.1038/sj.npp.1301256
  68. Roberts KF, Elbert DL, Kasten TP, Patterson BW, Sigurdson WC, Connors RE, Ovod V, Munsell LY, Mawuenyega KG, Miller-Thomas MM, et al. Amyloid-β efflux from the central nervous system into the plasma. Ann Neurol 2014;76:837-44. https://doi.org/10.1002/ana.24270
  69. Xiang Y, Bu XL, Liu YH, Zhu C, Shen LL, Jiao SS, Zhu XY, Giunta B, Tan J, Song WH, et al. Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer's disease. Acta Neuropathol 2015;130:487-99. https://doi.org/10.1007/s00401-015-1477-1
  70. Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress. Free Radic Biol Med 2002;32:1050-60. https://doi.org/10.1016/S0891-5849(02)00794-3
  71. Montine TJ, Neely MD, Quinn JF, Beal MF, Markesbery WR, Roberts LJ 2nd, Morrow JD. Lipid peroxidation in aging brain and Alzheimer's disease. Free Radic Biol Med 2002;33:620-6. https://doi.org/10.1016/S0891-5849(02)00807-9
  72. Gawel S, Wardas M, Niedworok E, Wardas P. Malondialdehyde (MDA) as a lipid peroxidation marker. Wiad Lek 2004;57:453-5.
  73. Choi SY, Lee J, Lee DG, Lee S, Cho EJ. Acer okamotoanum improves cognition and memory function in Aβ25-35-induced Alzheimer's mice model. Appl Biol Chem 2017;60:1-9. https://doi.org/10.1007/s13765-016-0244-x
  74. Hu J, Akama KT, Krafft GA, Chromy BA, Van Eldik LJ. Amyloid-β peptide activates cultured astrocytes: morphological alterations, cytokine induction and nitric oxide release. Brain Res 1998;785:195-206. https://doi.org/10.1016/S0006-8993(97)01318-8
  75. Law A, Gauthier S, Quirion R. Say NO to Alzheimer's disease: the putative links between nitric oxide and dementia of the Alzheimer's type. Brain Res Brain Res Rev 2001;35:73-96. https://doi.org/10.1016/S0165-0173(00)00051-5
  76. Wei T, Chen C, Hou J, Xin W, Mori A. Nitric oxide induces oxidative stress and apoptosis in neuronal cells. Biochim Biophys Acta 2000;1498:72-9. https://doi.org/10.1016/S0167-4889(00)00078-1
  77. Dubey M, Nagarkoti S, Awasthi D, Singh AK, Chandra T, Kumaravelu J, Barthwal MK, Dikshit M. Nitric oxide-mediated apoptosis of neutrophils through caspase-8 and caspase-3-dependent mechanism. Cell Death Dis 2016;7:e2348. https://doi.org/10.1038/cddis.2016.248
  78. Diaz A, De Jesus L, Mendieta L, Calvillo M, Espinosa B, Zenteno E, Guevara J, Limon ID. The amyloid-beta25-35 injection into the CA1 region of the neonatal rat hippocampus impairs the long-term memory because of an increase of nitric oxide. Neurosci Lett 2010;468:151-5. https://doi.org/10.1016/j.neulet.2009.10.087
  79. Ryu JH, Ahn H, Kim JY, Kim YK. Inhibitory activity of plant extracts on nitric oxide synthesis in LPS-activated macrophages. Phytother Res 2003;17:485-9. https://doi.org/10.1002/ptr.1180
  80. Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med 1997;23:134-47. https://doi.org/10.1016/S0891-5849(96)00629-6
  81. Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer's disease. Redox Biol 2018;14:450-64. https://doi.org/10.1016/j.redox.2017.10.014
  82. Diaz A, Trevino S, Pulido-Fernandez G, Martinez-Munoz E, Cervantes N, Espinosa B, Rojas K, Perez-Severiano F, Montes S, Rubio-Osornio M, et al. Epicatechin reduces spatial memory deficit caused by amyloid-β25-35 toxicity modifying the heat shock proteins in the CA1 region in the hippocampus of rats. Antioxidants 2019;8:113. https://doi.org/10.3390/antiox8050113
  83. Leutner S, Eckert A, Muller WE. ROS generation, lipid peroxidation and antioxidant enzyme activities in the aging brain. J Neural Transm (Vienna) 2001;108:955-67. https://doi.org/10.1007/s007020170015
  84. Wojsiat J, Zoltowska KM, Laskowska-Kaszub K, Wojda U. oxidant/antioxidant imbalance in Alzheimer's disease: therapeutic and diagnostic prospects. Oxid Med Cell Longev 2018;2018:6435861. https://doi.org/10.1155/2018/6435861
  85. Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 2007;8:101-12. https://doi.org/10.1038/nrm2101