Abstract
There is an urge to hunt for therapeutic measures against the most rampant neurodegenerative disorder, i.e., Alzheimer’s disease (AD). Recent researches have revealed that dietary antioxidants have potential to combat AD through several antioxidative mechanisms. Oxidative stress, a pathological hallmark of AD occurs mainly through increased free radical production and needs to be targeted and controlled in order to treat AD. Prevention of β-amyloid aggregation is another challenge. Aggregation of amyloid β-protein strongly contributes to the AD pathogenesis. Use of antioxidants can prove to be a hopeful approach to neuroprotection as they have tendency to reduce destructive effects of reactive oxygen species (ROS). Antioxidants keep the equilibrium between the physiological generation of ROS and their normalization. These constitute a major portion of drugs that are presently under investigation for AD pathology. Herein, we have summarized the therapeutic nature of natural antioxidants towards AD. A variety of dietary antioxidants have been chosen to discuss their basic chemical properties, potential towards ROS scavenging, and inhibition of Aβ aggregation. Role of these antioxidants in the management of neurodegenerative disorders have been reviewed on the basis of preclinical and clinical evidences. It has been proved that dietary antioxidants certainly play a crucial role in treatment of AD but strong clinical evidences are still lacking.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hroudova J, Singh N, Fisar Z. Mitochondrial dysfunctions in neurodegenerative diseases: relevance to Alzheimer’s disease. Biomed Res Int. 2014;2014:1–9.
Weiner M, Veitch DP, Aisen PS, Beckett LA, Cairns NJ. Recent publications from the Alzheimer’s disease neuroimaging initiative: reviewing progress toward improved AD clinical trials. Alzheimers Dement. 2017;13:e1–e85.
Price DL, Tanzi RE, Borchelt DR, Sisodia SS. Alzheimer’s disease: genetic studies and transgenic models. Annu Rev Genet. 1998;32:461–93.
Duan H, Jiang J, Xu J, Zhou H, Huang Z, Yu Z, Yan Z. Differences in Aβ brain networks in Alzheimer’s disease and healthy controls. Brain Res. 2017;1655:77–89.
Aguiar J, Costa R, Rocha F, Estevinho BN, Santos L. Design of microparticles containing natural antioxidants: preparation, characterization and controlled release studies. Powder Technol. 2017;313:287–92.
Choi DY, Lee YJ, Hong JT, Lee HJ. Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer’s disease. Brain Res Bull. 2012;87:144–53.
Xu P, Zhang M, Sheng R, Ma Y. Synthesis and biological evaluation of deferiprone-resveratrol hybrids as antioxidants, Aβ1–42 aggregation inhibitors and metal-chelating agents for Alzheimer’s disease. Eur J Med Chem. 2017;127:174–86.
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408:239–47.
Kenjiro O, Tsuyoshi H, Naiki H, Yamada M. Anti-amyloidogenic effects of antioxidants: implications for the prevention and therapeutics of Alzheimer’s disease. Biochim Biophys Acta. 2006;1762:575–86.
Mattson MP. Pathways towards and from Alzheimer’s disease. Nature. 2004;430:631–9.
Sies H. Strategies of antioxidant defense. Eur J Biochem. 1993;215:213–9.
Reddy PH. Mitochondrial oxidative damage in aging and Alzheimer’s disease: implications for mitochondrially targeted antioxidant therapeutics. J Biomed Biotechnol. 2006;2006:1–13.
Kostova AT, Talalay P. Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol Nutr Food Res. 2008;52:S128–38.
Mecocci P, Polidori MC, Cherubini A, et al. Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease. Arch Neurol. 2002;59:794–8.
Rinaldi P, Polidori MC, Metastasio A, et al. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging. 2003;24:915–9.
Kim DO, Lee CY. Comprehensive study on vitamin C equivalent antioxidant capacity (VCEAC) of various polyphenolics in scavenging a free radical and its structural relationship. Crit Rev Food Sci Nutr. 2004;44:253–73.
Luchsinger JA, Tang MX, Shea S, et al. Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol. 2003;60:203–8.
Evatt ML, DeLong MR, Khazai N. Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol. 2008;65:1348–52.
Yatin SM, Varadarajan S, Butterfield DA. Vitamin E prevents Alzheimer’s amyloid ß-peptide (1-42)-induced neuronal protein oxidation and reactive oxygen species production. J Alzheimer Dis. 2000;2:123–31.
Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements The Cache County Study. Arch Neurol. 2004;61:82–8.
Wang HX, Wahlin A, Basun H, et al. Vitamin B12 and folate in relation to the development of Alzheimer’s disease. Neurology. 2001;56:1188–94.
Aisen PS, Schneider LS, Sano M, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease a randomized controlled trial. JAMA. 2008;300:1774–83.
Quadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M, Lucca U. Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am J Clin Nutr. 2004;80:114–22.
Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hoffman A, Witteman JCM, Breteler MMB. Dietary intake of antioxidant and risk of Alzheimer’s disease. JAMA. 2002;287:3223–9.
Morris MC, Beckett LA, Scherr PA, et al. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord. 1998;12:121–6.
Isaac MG, Quinn R, Tabet N. Vitamin E for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst Rev. 2008;(3):CD002854. https://doi.org/10.1002/14651858.CD002854.pub2.
Douad G, Refsum H, Jager CAD, et al. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci. 2013;110:9523–8.
Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med. 1997;336:1216–122.
Oken BS, Storzbach DM, Kaye JA. Ginkgo biloba extract improves cognitive function in mild to moderate Alzheimer’s disease. Arch Neurol. 1998;55:1409–15.
Rosick ER. Ginkgo biloba has multiple effects on Alzheimer’s disease. Life Enhancement. Magazine; May 2002.
Wang BS, Wang H, Song YY, et al. Effectiveness of standardized Ginkgo biloba extract on cognitive symptoms of dementia with a six-month treatment: a bivariate random effect meta-analysis. Pharmacopsychiatry. 2010;44:86–91.
Yang Z, Li W, Huang T, Chen J, Zhang X. Meta-analysis of Ginkgo biloba extract for the treatment of Alzheimer’s disease. Neural Regener Res. 2012;6:1125–9.
Shi C, Liu J, Wu F, Yew DT. Ginkgo biloba extract in Alzheimer’s disease: from action mechanisms to medical practice. Int J Mol Sci. 2010;11:107–23.
Vellas N, Coley N, Ousset PJ, Berrt G, Dartigues JF, Dubois B, Grandjean H. Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol. 2012;11:851–9.
Singh M, Arseneault M, Sanderson T, et al. Challenges for research on polyphenols from foods in Alzheimer’s disease: bioavailability, metabolism, and cellular and molecular mechanisms. J Agric Food Chem. 2008;56:4855–73.
Choi YT, Jung CH, Lee SR, et al. The green tea polyphenol (−)-epigallocatechingallate attenuates betaamyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci. 2001;70:603–14.
Lee JW, Lee YK, Ban JO, et al. Green tea (−)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappa B pathways in mice. J Nutr. 2009;139:1987–93.
Assuncao M, Marques MJS, Carvalho F, et al. Chronic green tea consumption prevents age-related changes in rat hippocampal formation. Neurobiol Aging. 2011;32:707–17.
Mandel SA, Amit T, Weinreb O, et al. Simultaneous manipulation of multiple brain targets by green tea catechins: a potential neuroprotective strategy for Alzheimer and Parkinson diseases. CNS Neurosci Ther. 2008;14:352–65.
Levites Y, Weinre O, Maor G, et al. Green tea polyphenol (−)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J Neurochem. 2001;78:1073–82.
Jin CF, Shen SR Sr, Zhao BL. Different effects of five catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells. J Agric Food Chem. 2001;49:6033–8.
Guo Q, Zhao B, Li M, et al. Studies on protective mechanisms of four components of green tea polyphenols against lipid peroxidation in synaptosomes. Biochim Biophys Acta. 1996;1304:210–22.
Levites Y, Amit T, Mandel S, et al. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (−)-epigallocatechin-3-gallate. FASEB J. 2003;17:952–4.
Bastianetto S, Yao ZX, Papadopoulos V, et al. Neuroprotective effects of green and black teas and their catechingallate esters against beta-amyloid induced toxicity. Eur J Neurosci. 2006;23:55–64.
Kuriyama S, Hozawa A, Ohmori K, Shimazu T, et al. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project. Am J Clin Nutr. 2006;83(2):355–61.
Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT, Swanson PD. Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol. 2002;155:732–8.
Seeram NP. Berry fruits: compositional elements, biochemical activities, and the impact of their intake on human health, performance, and disease. J Agric Food Chem. 2008;56:627–9.
Subash S, Essa MM, Adawi S, Memon M, Manivasagam T, Akbar M. Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regen Res. 2014;9:1557–66.
Galli RL, Bielinski DF, Szprengiel A, et al. Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection. Neurobiol Aging. 2006;27:344–50.
Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol. 2006;545:51–64.
Papandreou MA, Dimakopoulou A, Linardaki ZI, et al. Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity. Behav Brain Res. 2009;198:352–8.
Joseph JA, Arendash G, Gordon M, et al. Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer Disease Model. Nutr Neurosci. 2003;6:153–62.
Ono K, Hasegawa K, Naiki H, et al. Anti-amyloidogenic activity of tannic acid and its activity to destabilize Alzheimer’s β-amyloid fibrils in vitro. BBA Mol Basis Dis. 2004;1690:193–202.
Mori T, Zadeh KR, Koyam N, et al. Tannic acid is a natural β-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice. J Biol Chem. 2012;287:6912–27.
Bastianetto S, Krantic S, Quirion R, et al. Polyphenols as potential inhibitors of amyloid aggregation and toxicity: possible significance to Alzheimer’s disease. J Med Chem. 2008;8:429–35.
Pudio R, Bravo L, Calixto FL. Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. J Agric Food Chem. 2000;48:3396–402.
Hamaguchi T, Ono K, Murase A, et al. Phenolic compounds prevent Alzheimer’s pathology through different effects on the amyloid-β aggregation pathway. Am J Pathol. 2009;175:2557–65.
Kim DS, Park SY, Kim JK. Curcuminoids from Curcuma longa L. (Zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from betaA(1–42) insult. Neurosci Lett. 2001;303:57–61.
Ahmed T, Gilani AH, Hosseinmardi N, et al. Curcuminoids rescue long-term potentiation impaired by amyloid peptide in rat hippocampal slices. Synapse. 2011;65:572–82.
Lim GP, Chu T, Yang F, et al. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001;21:8370–7.
Evans AM, Fornasini G. Pharmacokinetics of L carnitine. Clin Pharmacokinet. 2003;42:941–67.
Calvini M, Carta A, Benedetti N, Iannuccelli M, Caruso G. Action of acetyl-L-carnitine in neurodegeneration and Alzheimer’s disease. Aging Cell Def Mech. 1992;663:483–6.
Tagliatela G, Angelucci L, Ramacci MT, Perez KW, Jackson GR, Polo JRP. Acetyl-l-carnitine enhances the response of PC12 cells to nerve growth factor. Dev Brain Res. 1991;59:221–30.
Shenk JC, Liu J, Fischbach K, Xu K, Puchowicz M, Obrenovich ME, Gasimov E, Alvarez LM, Ames BN, LaManna JC, Aliev G. The effect of acetyl-L-carnitine and R-α-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer’s disease. J Neurol Sci. 2009;283:199–206.
Das DK, Mukherjee S, Ray D. Resveratrol and red wine, healthy heart and longevity. Heart Fail Rev. 2010;15:467–77.
Kennedy DO, Wightman EL, Reay JL, et al. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010;91:1590–7.
Moosmann B, Skutella T, Beyer K, et al. Protective activity of aromatic amines and imines against oxidative nerve cell death. Biol Chem. 2001;382:1601–12.
Virgili M, Contestabile A. Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats. Neurosci Lett. 2000;281:123–6.
Shraddha DR, Thangiah G, Gerad DG, Tom LB, Jeganathan RB. Neuroprotective effects of resveratrol in Alzheimer disease pathology. Front Aging Neurosci. 2014;6:218.
Shay KP, Moreau RF, Smith EJ, et al. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790:1149–60.
Holmquist L, Stuchbury G, Berbaum K, et al. Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Pharmacol Ther. 2007;113:154–64.
Sandra LS, Gemma C, Kate MW, Miguel AP, Atwood CS, Smith MA, Perry G. Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer’s disease. Free Radic Res. 2009;43:156–64.
Staehelin HB. Micronutrients and Alzheimer’s disease. Proc Nutr Soc. 2005;64:565–70.
Yang X, Qiang X, Li Y, Luo L, Xu R, et al. Pyridoxine-resveratrol hybrids Mannich base derivatives as novel dual inhibitors of AChE and MAO-B with antioxidant and metal-chelating properties for the treatment of Alzheimer’s disease. Biorg Chem. 2017;71:305–14.
Dgachi Y, Sokolov O, Luzet V, et al. Tetrahydropyranodiquinolin-8-amines as new, non hepatotoxic, antioxidant, and acetylcholinesterase inhibitors for Alzheimer’s disease therapy. Eur J Med Chem. 2017;126:576–58.
Acknowledgements
The authors acknowledge Department of chemistry, Pt. Ravishankar Shukla University, Raipur and Department of Chemistry, Indian Institute of Technology, Bombay.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Singh, N., Ghosh, K.K. (2019). Recent Advances in the Antioxidant Therapies for Alzheimer’s Disease: Emphasis on Natural Antioxidants. In: Singh, S., Joshi, N. (eds) Pathology, Prevention and Therapeutics of Neurodegenerative Disease. Springer, Singapore. https://doi.org/10.1007/978-981-13-0944-1_22
Download citation
DOI: https://doi.org/10.1007/978-981-13-0944-1_22
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-0943-4
Online ISBN: 978-981-13-0944-1
eBook Packages: MedicineMedicine (R0)