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Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Review Article

An Increasing Role of Polyphenols as Novel Therapeutics for Alzheimer’s: A Review

Author(s): Nasiara Karim, Haroon Khan*, Imran Khan, Ouyang Guo, Eduardo Sobarzo-Sánchez, Luca Rastrelli and Mohammad A. Kamal

Volume 16, Issue 8, 2020

Page: [1007 - 1021] Pages: 15

DOI: 10.2174/1573406415666191105154407

Price: $65

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, with approximately 29 million older people suffering from this disease worldwide. This number is expected to become triple by 2050. AD is a complex and multifactorial neurodegenerative condition, characterized by complex pathology including oxidative stress, formation of aggregates of amyloid and tau, enhanced immune responses, metal deposition and disturbances in cholinesterase enzymes. There is no effective pharmacological treatment for combating the disease to date. The ineffectiveness of current pharmacological interventions in AD has led scientists to search for more safe and effective alternative therapeutic agents. Thus, natural products have become an important avenue for drug discovery in AD research. In this regard, polyphenols are natural products that have been shown to be effective in the modulation of the type of neurodegenerative changes seen in AD, suggesting a possible therapeutic role. The present review focuses on the chemistry of polyphenols, clinical studies for evaluating polyphenols as effective alternatives in AD treatment, cellular and molecular aspects of polyphenols in improving cognitive deficits and the current challenges and futuristic approaches to use polyphenols as safe and effective therapeutic agents in AD treatment.

Keywords: Alzheimer's disease, polyphenols, flavonoids, dementia, neuroprotection cellular mechanism, neurodegenerative disorders.

Graphical Abstract
[1]
Atukeren, P.; Cengiz, M.; Yavuzer, H.; Gelisgen, R.; Altunoglu, E.; Oner, S.; Erdenen, F.; Yuceakın, D.; Derici, H.; Cakatay, U.; Uzun, H. The efficacy of donepezil administration on acetylcholinesterase activity and altered redox homeostasis in Alzheimer’s disease. Biomed. Pharmacother., 2017, 90, 786-795.
[http://dx.doi.org/10.1016/j.biopha.2017.03.101] [PMID: 28427041]
[2]
Tarawneh, R.; Holtzman, D.M. The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb. Perspect. Med., 2012, 2(5), a006148.
[http://dx.doi.org/10.1101/cshperspect.a006148] [PMID: 22553492]
[3]
Benazzi, F. Agitated depression in bipolar II disorder. World J. Biol. Psychiatry, 2005, 6(3), 198-205.
[http://dx.doi.org/10.1080/15622970510029858] [PMID: 16166029]
[4]
Blass, J.P.; Ko, L.; Wisniewski, H.M. Pathology of Alzheimer’s disease. Psychiatr. Clin. North Am., 1991, 14(2), 397-420.
[http://dx.doi.org/10.1016/S0193-953X(18)30315-0] [PMID: 2062726]
[5]
Rauf, A.; Hadda, T.B.; Uddin, G.; Cerón-Carrasco, J.P.; Peña-García, J.; Pérez-Sánchez, H.; Khan, H.; Bawazeer, S.; Patel, S.; Mubarak, M.S.; Abu-Izneid, T.; Mabkhot, Y.N. Sedative-hypnotic-like effect and molecular docking of di-naphthodiospyrol from Diospyros lotus in an animal model. Biomed. Pharmacother., 2017, 88, 109-113.
[http://dx.doi.org/10.1016/j.biopha.2017.01.043] [PMID: 28103503]
[6]
Bakhtiari, M.; Panahi, Y.; Ameli, J.; Darvishi, B. Protective effects of flavonoids against Alzheimer’s disease-related neural dysfunctions. Biomed. Pharmacother., 2017, 93(Suppl. C), 218-229.
[http://dx.doi.org/10.1016/j.biopha.2017.06.010] [PMID: 28641164]
[7]
Chonpathompikunlert, P.; Wattanathorn, J.; Muchimapura, S. Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer’s disease. Food Chem. Toxicol., 2010, 48(3), 798-802.
[http://dx.doi.org/10.1016/j.fct.2009.12.009] [PMID: 20034530]
[8]
Muhammad, N.; Saeed, M.; Khan, H.; Adhikari, A.; Muhammad, K. Muscle relaxant and sedative-hypnotic activity of extract of Viola betonicifolia in animal models supported by its isolated compound, 4-hydroxy coumarin. J. Chem., 2013, 2013, 1-6.
[9]
Nabavi, S.F.; Khan, H.; D’Onofrio, G.; Šamec, D.; Shirooie, S.; Dehpour, A.R. Apigenin as neuroprotective agent: Of mice and men. Pharmacol. Res., 2018, 128, 359-365.
[http://dx.doi.org/10.1016/j.phrs.2017.10.008] [PMID: 29055745]
[10]
Zetterberg, H.; Blennow, K.; Hanse, E. Amyloid beta and APP as biomarkers for Alzheimer’s disease. Exp. Gerontol., 2010, 45(1), 23-29.
[http://dx.doi.org/10.1016/j.exger.2009.08.002] [PMID: 19698775]
[11]
Heston, L.L. Down’s syndrome and Alzheimer’s dementia: defining an association. Psychiatr. Dev., 1984, 2(4), 287-294.
[PMID: 6241313]
[12]
Verdile, G.; Gandy, S.E.; Martins, R.N. The role of presenilin and its interacting proteins in the biogenesis of Alzheimer’s beta amyloid. Neurochem. Res., 2007, 32(4-5), 609-623.
[http://dx.doi.org/10.1007/s11064-006-9131-x] [PMID: 16944319]
[13]
Resende, R.; Ferreiro, E.; Pereira, C.; Resende de Oliveira, C. Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1-42: involvement of endoplasmic reticulum calcium release in oligomer-induced cell death. Neuroscience, 2008, 155(3), 725-737.
[http://dx.doi.org/10.1016/j.neuroscience.2008.06.036] [PMID: 18621106]
[14]
Radi, E.; Formichi, P.; Battisti, C.; Federico, A. Apoptosis and oxidative stress in neurodegenerative diseases. J. Alzheimers Dis., 2014, 42(Suppl. 3), S125-S152.
[http://dx.doi.org/10.3233/JAD-132738] [PMID: 25056458]
[15]
Lovestone, S. Fleshing out the amyloid cascade hypothesis: the molecular biology of Alzheimer’s disease. Dialogues Clin. Neurosci., 2000, 2(2), 101-110.
[PMID: 22033981]
[16]
Singh, S.K.; Srivastav, S.; Yadav, A.K.; Srikrishna, S.; Perry, G. Overview of Alzheimer’s disease and some therapeutic approaches targeting Aβ by using several synthetic and herbal compounds. Oxid. Med. Cell. Longev., 2016, 2016, 7361613.
[http://dx.doi.org/10.1155/2016/7361613] [PMID: 27034741]
[17]
Harry, G.J.; Kraft, A.D. Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment. Expert Opin. Drug Metab. Toxicol., 2008, 4(10), 1265-1277.
[http://dx.doi.org/10.1517/17425255.4.10.1265] [PMID: 18798697]
[18]
Maynard, C.J.; Bush, A.I.; Masters, C.L.; Cappai, R.; Li, Q.X. Metals and amyloid-beta in Alzheimer’s disease. Int. J. Exp. Pathol., 2005, 86(3), 147-159.
[http://dx.doi.org/10.1111/j.0959-9673.2005.00434.x] [PMID: 15910549]
[19]
Pérez-Jiménez, J.; Neveu, V.; Vos, F.; Scalbert, A. Systematic analysis of the content of 502 polyphenols in 452 foods and beverages: an application of the phenol-explorer database. J. Agric. Food Chem., 2010, 58(8), 4959-4969.
[http://dx.doi.org/10.1021/jf100128b] [PMID: 20302342]
[20]
Ignat, I.; Volf, I.; Popa, V.I. A critical review of methods for characterisation of polyphenolic compounds in fruits and vegetables. Food Chem., 2011, 126(4), 1821-1835.
[http://dx.doi.org/10.1016/j.foodchem.2010.12.026] [PMID: 25213963]
[21]
Heo, H.J.; Kim, D.O.; Shin, S.C.; Kim, M.J.; Kim, B.G.; Shin, D.H. Effect of antioxidant flavanone, naringenin, from Citrus junoson neuroprotection. J. Agric. Food Chem., 2004a, 52(6), 1520-1525.
[http://dx.doi.org/10.1021/jf035079g] [PMID: 15030205]
[22]
Hwang, S.L.; Yen, G.C. Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells. J. Agric. Food Chem., 2008, 56(3), 859-864.
[http://dx.doi.org/10.1021/jf072826r] [PMID: 18189359]
[23]
Candiracci, M.; Piatti, E.; Dominguez-Barragán, M.; García-Antrás, D.; Morgado, B.; Ruano, D.; Gutiérrez, J.F.; Parrado, J.; Castaño, A. Anti-inflammatory activity of a honey flavonoid extract on lipopolysaccharide-activated N13 microglial cells. J. Agric. Food Chem., 2012, 60(50), 12304-12311.
[http://dx.doi.org/10.1021/jf302468h] [PMID: 23176387]
[24]
Murillo, E.; Britton, G.B.; Durant, A.A. Antioxidant activity and polyphenol content in cultivated and wild edible fruits grown in Panama. J. Pharm. Bioallied Sci., 2012, 4(4), 313-317.
[http://dx.doi.org/10.4103/0975-7406.103261] [PMID: 23248565]
[25]
Tangney, C.C.; Rasmussen, H.E. Polyphenols, inflammation, and cardiovascular disease. Curr. Atheroscler. Rep., 2013, 15(5), 324.
[http://dx.doi.org/10.1007/s11883-013-0324-x] [PMID: 23512608]
[26]
Bravo, L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr. Rev., 1998, 56(11), 317-333.
[http://dx.doi.org/10.1111/j.1753-4887.1998.tb01670.x] [PMID: 9838798]
[27]
Manach, C.; Scalbert, A.; Morand, C. RÃmÃsy, C.; JimÃnez, L. Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr., 2004, 79, 727-747.
[28]
Youdim, K.A.; Shukitt-Hale, B.; Joseph, J.A. Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic. Biol. Med., 2004, 37(11), 1683-1693.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.08.002] [PMID: 15528027]
[29]
Beecher, G.R. Overview of dietary flavonoids: nomenclature, occurrence and intake. J. Nutr., 2003, 133(10), 3248S-3254S.
[http://dx.doi.org/10.1093/jn/133.10.3248S] [PMID: 14519822]
[30]
Harborne, J.; Mabry, T.J.; Mabry, H. The Flavonoids; Academic Press: New York, 1975.
[http://dx.doi.org/10.1007/978-1-4899-2909-9]
[31]
Lamartiniere, C.A. Protection against breast cancer with genistein: a component of soy. Am. J. Clin. Nutr., 2000, 71(6)(Suppl.), 1705S-1707S.
[http://dx.doi.org/10.1093/ajcn/71.6.1705S] [PMID: 10837323]
[32]
Ohno, T.; Kato, N.; Ishii, C.; Shimizu, M.; Ito, Y.; Tomono, S.; Kawazu, S. Genistein augments cyclic adenosine 3‘5’-monophosphate(cAMP) accumulation and insulin release in MIN6 cells. Endocr. Res., 1993, 19(4), 273-285.
[http://dx.doi.org/10.1080/07435809309026682] [PMID: 7508378]
[33]
Berhow, M.; Tisserat, B.; Kanes, K.; Vandercook, C. Survey of phenolic compounds produced in citrus Technical Bulletin 1856. U.S. Department of Agriculture, Agricultural Research Service, Peoria IL, 1998.
[34]
Vauzour, D.; Vafeiadou, K.; Rodriguez-Mateos, A.; Rendeiro, C.; Spencer, J.P. The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr., 2008, 3(3-4), 115-126.
[http://dx.doi.org/10.1007/s12263-008-0091-4] [PMID: 18937002]
[35]
Dodd, G.F. The acute effects of flavonoid-rich blueberries on cognitive function in healthy younger and older adults. Doctoral; University of Reading, 2012.
[36]
Whyte, A.R.; Schafer, G.; Williams, C.M. Cognitive effects following acute wild blueberry supplementation in 7- to 10-year-old children. Eur. J. Nutr., 2016, 55(6), 2151-2162.
[http://dx.doi.org/10.1007/s00394-015-1029-4] [PMID: 26437830]
[37]
Watson, A.W.; Haskell-Ramsay, C.F.; Kennedy, D.O.; Cooney, J.M.; Trower, T.; Scheepens, A. Acute supplementation with blackcurrant extracts modulates cognitive functioning and inhibits monoamine oxidase-B in healthy young adults. J. Funct. Foods, 2015, 17, 524-539.
[http://dx.doi.org/10.1016/j.jff.2015.06.005]
[38]
Caldwell, K.; Charlton, K.E.; Roodenrys, S.; Jenner, A. Anthocyaninrich cherry juice does not improve acute cognitive performance on RAVLT. Nutr. Neurosci., 2016, 19(9), 423-424.
[39]
Lamport, D.J.; Pal, D.; Macready, A.L.; Barbosa-Boucas, S.; Fletcher, J.M.; Williams, C.M.; Spencer, J.P.; Butler, L.T. The effects of flavanone-rich citrus juice on cognitive function and cerebral blood flow: an acute, randomised, placebo-controlled cross-over trial in healthy, young adults. Br. J. Nutr., 2016, 116(12), 2160-2168.
[http://dx.doi.org/10.1017/S000711451600430X] [PMID: 28091350]
[40]
Mandel, S.A.; Amit, T.; Kalfon, L.; Reznichenko, L.; Weinreb, O.; Youdim, M.B. Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: special reference to epigallocatechin gallate (EGCG). J. Alzheimers Dis., 2008, 15(2), 211-222.
[http://dx.doi.org/10.3233/JAD-2008-15207] [PMID: 18953110]
[41]
Schroeter, H.; Bahia, P.; Spencer, J.P.; Sheppard, O.; Rattray, M.; Cadenas, E.; Rice-Evans, C.; Williams, R.J. (-)Epicatechin stimulates ERK-dependent cyclic AMP response element activity and up-regulates GluR2 in cortical neurons. J. Neurochem., 2007, 101(6), 1596-1606.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04434.x] [PMID: 17298385]
[42]
Bliss, T.V.; Collingridge, G.L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 1993, 361(6407), 31-39.
[http://dx.doi.org/10.1038/361031a0] [PMID: 8421494]
[43]
Khan, H.; Saeed, M.; Muhammad, N.; Khan, F.; Ibrar, M.; Hassan, S.; Shah, W.A. Report: Comprehensive nutrients analysis of rhizomes of Polygonatum verticillatum. Pak. J. Pharm. Sci., 2012, 25(4), 871-875.
[PMID: 23010008]
[44]
Spagnuolo, C.; Moccia, S.; Russo, G.L. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur. J. Med. Chem., 2018, 153, 105-115.
[PMID: 28923363]
[45]
Vauzour, D. Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxid. Med. Cell. Longev., 2012, 2012, 914273.
[http://dx.doi.org/10.1155/2012/914273] [PMID: 22701758]
[46]
Impey, S.; Smith, D.M.; Obrietan, K.; Donahue, R.; Wade, C.; Storm, D.R. Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat. Neurosci., 1998, 1(7), 595-601.
[http://dx.doi.org/10.1038/2830] [PMID: 10196567]
[47]
Spencer, J.P.E.; Vauzour, D.; Rendeiro, C. Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. Arch. Biochem. Biophys., 2009, 492(1-2), 1-9.
[http://dx.doi.org/10.1016/j.abb.2009.10.003] [PMID: 19822127]
[48]
Alonso, M.; Bekinschtein, P.; Cammarota, M.; Vianna, M.R.; Izquierdo, I.; Medina, J.H. Endogenous BDNF is required for long-term memory formation in the rat parietal cortex. Learn. Mem., 2005, 12(5), 504-510.
[http://dx.doi.org/10.1101/lm.27305] [PMID: 16204202]
[49]
Mansuri, M.L.; Parihar, P.; Solanki, I.; Parihar, M.S. Flavonoids in modulation of cell survival signalling pathways. Genes Nutr., 2014, 9(3), 400.
[http://dx.doi.org/10.1007/s12263-014-0400-z] [PMID: 24682883]
[50]
Yin, Y.; Edelman, G.M.; Vanderklish, P.W. The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes. Proc. Natl. Acad. Sci. USA, 2002, 99(4), 2368-2373.
[http://dx.doi.org/10.1073/pnas.042693699] [PMID: 11842217]
[51]
Waltereit, R.; Dammermann, B.; Wulff, P.; Scafidi, J.; Staubli, U.; Kauselmann, G.; Bundman, M.; Kuhl, D. Arg3.1/Arc mRNA induction by Ca2+ and cAMP requires protein kinase A and mitogen-activated protein kinase/extracellular regulated kinase activation. J. Neurosci., 2001, 21(15), 5484-5493.
[http://dx.doi.org/10.1523/JNEUROSCI.21-15-05484.2001] [PMID: 11466419]
[52]
Vafeiadou, K.; Vauzour, D.; Spencer, J.P. Neuroinflammation and its modulation by flavonoids. Endocr. Metab. Immune Disord. Drug Targets, 2007, 7(3), 211-224.
[http://dx.doi.org/10.2174/187153007781662521] [PMID: 17897048]
[53]
Szekely, C.A.; Thorne, J.E.; Zandi, P.P.; Ek, M.; Messias, E.; Breitner, J.C.; Goodman, S.N. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer’s disease: a systematic review. Neuroepidemiology, 2004, 23(4), 159-169.
[http://dx.doi.org/10.1159/000078501] [PMID: 15279021]
[54]
Cuevas, A.; Saavedra, N.; Salazar, L.A.; Abdalla, D.S. Modulation of immune function by polyphenols: possible contribution of epigenetic factors. Nutrients, 2013, 5(7), 2314-2332.
[http://dx.doi.org/10.3390/nu5072314] [PMID: 23812304]
[55]
González-Gallego, J.; García-Mediavilla, M.V.; Sánchez-Campos, S.; Tuñón, M.J. Fruit polyphenols, immunity and inflammation. Br. J. Nutr., 2010, 104(Suppl. 3), S15-S27.
[http://dx.doi.org/10.1017/S0007114510003910] [PMID: 20955647]
[56]
Panahi, Y.; Darvishi, B.; Ghanei, M.; Jowzi, N.; Beiraghdar, F.; Varnamkhasti, B.S. Molecular mechanisms of curcumins suppressing effects on tumorigenesis, angiogenesis and metastasis, focusing on NF-κB pathway. Cytokine Growth Factor Rev., 2016, 28, 21-29.
[http://dx.doi.org/10.1016/j.cytogfr.2015.12.004] [PMID: 26774676]
[57]
Gage, F.H. Mammalian neural stem cells. Science, 2000, 287(5457), 1433-1438.
[http://dx.doi.org/10.1126/science.287.5457.1433] [PMID: 10688783]
[58]
van Praag, H.; Lucero, M.J.; Yeo, G.W.; Stecker, K.; Heivand, N.; Zhao, C.; Yip, E.; Afanador, M.; Schroeter, H.; Hammerstone, J.; Gage, F.H. Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J. Neurosci., 2007, 27(22), 5869-5878.
[http://dx.doi.org/10.1523/JNEUROSCI.0914-07.2007] [PMID: 17537957]
[59]
Ding, X.; Ouyang, M-A.; Liu, X.; Wang, R-Z. Acetylcholinesterase inhibitory activities of flavonoids from the leaves of ginkgo biloba against brown planthopper. J. Chem., 2013, 2013, 4.
[http://dx.doi.org/10.1155/2013/645086]
[60]
Cui, Y.M.; Ao, M.Z.; Li, W.; Yu, L.J. Effect of glabridin from Glycyrrhiza glabra on learning and memory in mice. Planta Med., 2008, 74(4), 377-380.
[http://dx.doi.org/10.1055/s-2008-1034319] [PMID: 18484526]
[61]
He, X.L.; Zhou, W.Q.; Bi, M.G.; Du, G.H. Neuroprotective effects of icariin on memory impairment and neurochemical deficits in senescence-accelerated mouse prone 8 (SAMP8) mice. Brain Res., 2010, 1334, 73-83.
[http://dx.doi.org/10.1016/j.brainres.2010.03.084] [PMID: 20380820]
[62]
Kumar, A.; Prakash, A.; Dogra, S. Naringin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress induced by D-galactose in mice. Food Chem. Toxicol., 2010b, 48(2), 626-632.
[http://dx.doi.org/10.1016/j.fct.2009.11.043] [PMID: 19941926]
[63]
Balez, R.; Steiner, N.; Engel, M.; Muñoz, S.S.; Lum, J.S.; Wu, Y.; Wang, D.; Vallotton, P.; Sachdev, P.; O’Connor, M.; Sidhu, K.; Münch, G.; Ooi, L. Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Sci. Rep., 2016, 6, 31450.
[http://dx.doi.org/10.1038/srep31450] [PMID: 27514990]
[64]
Priprem, A.; Watanatorn, J.; Sutthiparinyanont, S.; Phachonpai, W.; Muchimapura, S. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomedicine (Lond.), 2008, 4(1), 70-78.
[http://dx.doi.org/10.1016/j.nano.2007.12.001] [PMID: 18249157]
[65]
Kanter, M.; Unsal, C.; Aktas, C.; Erboga, M. Neuroprotective effect of quercetin against oxidative damage and neuronal apoptosis caused by cadmium in hippocampus. Toxicol. Ind. Health, 2016, 32(3), 541-550.
[http://dx.doi.org/10.1177/0748233713504810] [PMID: 24193051]
[66]
García-Mediavilla, V.; Crespo, I.; Collado, P.S.; Esteller, A.; Sánchez-Campos, S.; Tuñón, M.J.; González-Gallego, J. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur. J. Pharmacol., 2007, 557(2-3), 221-229.
[http://dx.doi.org/10.1016/j.ejphar.2006.11.014] [PMID: 17184768]
[67]
Sabogal-Guáqueta, A.M.; Muñoz-Manco, J.I.; Ramírez-Pineda, J.R.; Lamprea-Rodriguez, M.; Osorio, E.; Cardona-Gómez, G.P. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology, 2015, 93, 134-145.
[http://dx.doi.org/10.1016/j.neuropharm.2015.01.027] [PMID: 25666032]
[68]
Kim, J.H.; Lee, J.; Lee, S.; Cho, E.J. Quercetin and quercetin-3-β-d-glucoside improve cognitive and memory function in Alzheimer’s disease mouse. Appl. Biol. Chem., 2016, 59(5), 721-728.
[http://dx.doi.org/10.1007/s13765-016-0217-0]
[69]
Garg, A.; Garg, S.; Zaneveld, L.J.; Singla, A.K. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother. Res., 2001, 15(8), 655-669.
[http://dx.doi.org/10.1002/ptr.1074] [PMID: 11746857]
[70]
Huang, S.M.; Tsai, S.Y.; Lin, J.A.; Wu, C.H.; Yen, G.C. Cytoprotective effects of hesperetin and hesperidin against amyloid β-induced impairment of glucose transport through downregulation of neuronal autophagy. Mol. Nutr. Food Res., 2012, 56(4), 601-609.
[http://dx.doi.org/10.1002/mnfr.201100682] [PMID: 22383310]
[71]
Mandel, S.; Youdim, M.B. Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic. Biol. Med., 2004, 37(3), 304-317.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.04.012] [PMID: 15223064]
[72]
Rainey-Smith, S.; Schroetke, L.W.; Bahia, P.; Fahmi, A.; Skilton, R.; Spencer, J.P.; Rice-Evans, C.; Rattray, M.; Williams, R.J. Neuroprotective effects of hesperetin in mouse primary neurones are independent of CREB activation. Neurosci. Lett., 2008, 438(1), 29-33.
[http://dx.doi.org/10.1016/j.neulet.2008.04.056] [PMID: 18467030]
[73]
Matias, I.; Diniz, L.P.; Buosi, A.; Neves, G.; Stipursky, J.; Gomes, F.C.A. Flavonoid hesperidin induces synapse formation and improves memory performance through the astrocytic TGF-β1. Front. Aging Neurosci., 2017, 9(184), 184.
[http://dx.doi.org/10.3389/fnagi.2017.00184] [PMID: 28659786]
[74]
Lee, H.; Bae, J.H.; Lee, S.R. Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils. J. Neurosci. Res., 2004, 77(6), 892-900.
[http://dx.doi.org/10.1002/jnr.20193] [PMID: 15334607]
[75]
Wang, J.Y. Nucleo-cytoplasmic communication in apoptotic response to genotoxic and inflammatory stress. Cell Res., 2005, 15(1), 43-48.
[http://dx.doi.org/10.1038/sj.cr.7290263] [PMID: 15686626]
[76]
Levites, Y.; Amit, T.; Mandel, S.; Youdim, M.B. 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(8), 952-954.
[http://dx.doi.org/10.1096/fj.02-0881fje] [PMID: 12670874]
[77]
Chang, C-C.; Li, H.H.; Chang, Y.T.; Ho, Y.J.; Hsieh, L.J.; Chiu, P.Y.; Cheng, Y.S.; Lin, C.L.; Lai, T.J. Aβ exacerbates α-synuclein-induced neurotoxicity through impaired insulin signaling in α-synuclein-overexpressed human SK-N-MC neuronal cells. CNS Neurosci. Ther., 2018, 24(1), 47-57.
[http://dx.doi.org/10.1111/cns.12772] [PMID: 29092095]
[78]
Cheng-Chung Wei, J.; Huang, H.C.; Chen, W.J.; Huang, C.N.; Peng, C.H.; Lin, C.L. Epigallocatechin gallate attenuates amyloid β-induced inflammation and neurotoxicity in EOC 13.31 microglia. Eur. J. Pharmacol., 2016, 770, 16-24.
[http://dx.doi.org/10.1016/j.ejphar.2015.11.048] [PMID: 26643169]
[79]
Chesser, A.S.; Ganeshan, V.; Yang, J.; Johnson, G.V. Epigallocatechin-3-gallate enhances clearance of phosphorylated tau in primary neurons. Nutr. Neurosci., 2016, 19(1), 21-31.
[http://dx.doi.org/10.1179/1476830515Y.0000000038] [PMID: 26207957]
[80]
Pandurangan, A.K.; Dharmalingam, P.; Ananda Sadagopan, S.K.; Ganapasam, S. Effect of luteolin on the levels of glycoproteins during azoxymethane-induced colon carcinogenesis in mice. Asian Pac. J. Cancer Prev., 2012, 13(4), 1569-1573.
[http://dx.doi.org/10.7314/APJCP.2012.13.4.1569] [PMID: 22799368]
[81]
Rezai-Zadeh, K.; Ehrhart, J.; Bai, Y.; Sanberg, P.R.; Bickford, P.; Tan, J.; Shytle, R.D. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J. Neuroinflammation, 2008, 5, 41.
[http://dx.doi.org/10.1186/1742-2094-5-41] [PMID: 18817573]
[82]
Yu, T.X.; Zhang, P.; Guan, Y.; Wang, M.; Zhen, M.Q. Protective effects of luteolin against cognitive impairment induced by infusion of Aβ peptide in rats. Int. J. Clin. Exp. Pathol., 2015, 8(6), 6740-6747.
[PMID: 26261557]
[83]
Wu, W.; Li, D.; Zong, Y.; Zhu, H.; Pan, D.; Xu, T.; Wang, T.; Wang, T. Luteolin inhibits inflammatory responses via p38/MK2/TTP-mediated mRNA stability. Molecules, 2013, 18(7), 8083-8094.
[http://dx.doi.org/10.3390/molecules18078083] [PMID: 23839113]
[84]
Guo, D.J.; Li, F.; Yu, P.H.; Chan, S.W. Neuroprotective effects of luteolin against apoptosis induced by 6-hydroxydopamine on rat pheochromocytoma PC12 cells. Pharm. Biol., 2013, 51(2), 190-196.
[http://dx.doi.org/10.3109/13880209.2012.716852] [PMID: 23035972]
[85]
Caltagirone, C.; Cisari, C.; Schievano, C.; Di Paola, R.; Cordaro, M.; Bruschetta, G.; Esposito, E.; Cuzzocrea, S. Stroke Study Group. Co-ultramicronized palmitoylethanolamide/luteolin in the treatment of cerebral ischemia: from rodent to man. Transl. Stroke Res., 2016, 7(1), 54-69.
[http://dx.doi.org/10.1007/s12975-015-0440-8] [PMID: 26706245]
[86]
Zhou, F.; Chen, S.; Xiong, J.; Li, Y.; Qu, L. Luteolin reduces zinc-induced tau phosphorylation at Ser262/356 in an ROS-dependent manner in SH-SY5Y cells. Biol. Trace Elem. Res., 2012, 149(2), 273-279.
[http://dx.doi.org/10.1007/s12011-012-9411-z] [PMID: 22528780]
[87]
Xu, S.Z.; Zhong, W.; Ghavideldarestani, M.; Saurabh, R.; Lindow, S.W.; Atkin, S.L. Multiple mechanisms of soy isoflavones against oxidative stress-induced endothelium injury. Free Radic. Biol. Med., 2009, 47(2), 167-175.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.04.021] [PMID: 19393315]
[88]
Nones, J.; Costa, A.P.; Leal, R.B.; Gomes, F.C.; Trentin, A.G. The flavonoids hesperidin and rutin promote neural crest cell survival. Cell Tissue Res., 2012, 350(2), 305-315.
[http://dx.doi.org/10.1007/s00441-012-1472-y] [PMID: 22855262]
[89]
Wang, R.; Sun, Y.; Huang, H.; Wang, L.; Chen, J.; Shen, W. Rutin, A Natural Flavonoid Protects PC12 Cells Against Sodium Nitroprusside-Induced Neurotoxicity Through Activating PI3K/Akt/mTOR and ERK1/2 Pathway. Neurochem. Res., 2015, 40(9), 1945-1953.
[http://dx.doi.org/10.1007/s11064-015-1690-2] [PMID: 26255195]
[90]
Simonyi, A.; Chen, Z.; Jiang, J.; Zong, Y.; Chuang, D.Y.; Gu, Z.; Lu, C.H.; Fritsche, K.L.; Greenlief, C.M.; Rottinghaus, G.E.; Thomas, A.L.; Lubahn, D.B.; Sun, G.Y. Inhibition of microglial activation by elderberry extracts and its phenolic components. Life Sci., 2015, 128, 30-38.
[http://dx.doi.org/10.1016/j.lfs.2015.01.037] [PMID: 25744406]
[91]
Rezai-Zadeh, K.; Ehrhart, J.; Bai, Y.; Sanberg, P.R.; Bickford, P.; Tan, J.; Shytle, R.D. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J. Neuroinflammation, 2008, 5, 41.
[http://dx.doi.org/10.1186/1742-2094-5-41] [PMID: 18817573]
[92]
Choi, J.Y.; Lee, J.M.; Lee, D.G.; Cho, S.; Yoon, Y.H.; Cho, E.J.; Lee, S. The n-butanol fraction and rutin from tartary buckwheat improve cognition and memory in an in vivo model of amyloid-β-induced Alzheimer’s disease. J. Med. Food, 2015, 18(6), 631-641.
[http://dx.doi.org/10.1089/jmf.2014.3292] [PMID: 25785882]
[93]
Nazir, N.; Karim, N.; Abdel-Halim, H.; Khan, I.; Wadood, S.F.; Nisar, M. Phytochemical analysis, molecular docking and antiamnesic effects of methanolic extract of Silybum marianum (L.) Gaertn seeds in scopolamine induced memory impairment in mice. J. Ethnopharmacol., 2018, 210(Suppl. C), 198-208.
[http://dx.doi.org/10.1016/j.jep.2017.08.026] [PMID: 28842342]
[94]
Rendeiro, C.; Vauzour, D.; Rattray, M.; Waffo-Téguo, P.; Mérillon, J.M.; Butler, L.T.; Williams, C.M.; Spencer, J.P. Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor. PLoS One, 2013, 8(5), e63535.
[http://dx.doi.org/10.1371/journal.pone.0063535] [PMID: 23723987]
[95]
Vepsäläinen, S.; Koivisto, H.; Pekkarinen, E.; Mäkinen, P.; Dobson, G.; McDougall, G.J.; Stewart, D.; Haapasalo, A.; Karjalainen, R.O.; Tanila, H.; Hiltunen, M. Anthocyanin-enriched bilberry and blackcurrant extracts modulate amyloid precursor protein processing and alleviate behavioral abnormalities in the APP/PS1 mouse model of Alzheimer’s disease. J. Nutr. Biochem., 2013, 24(1), 360-370.
[http://dx.doi.org/10.1016/j.jnutbio.2012.07.006] [PMID: 22995388]
[96]
Farooqui, T.; Farooqui, A. Neuroprotective Effects of Phytochemicals in Neurological Disorders; Wiley-Blackwell, 2017.
[http://dx.doi.org/10.1002/9781119155195]
[97]
Gutierres, J.M.; Carvalho, F.B.; Schetinger, M.R.C.; Agostinho, P.; Marisco, P.C.; Vieira, J.M.; Rosa, M.M.; Bohnert, C.; Rubin, M.A.; Morsch, V.M.; Spanevello, R.; Mazzanti, C.M. Neuroprotective effect of anthocyanins on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia in rats. Int. J. Dev. Neurosci., 2014, 33(Suppl. C), 88-97.
[http://dx.doi.org/10.1016/j.ijdevneu.2013.12.006] [PMID: 24374256]
[98]
Kelsey, N.; Hulick, W.; Winter, A.; Ross, E.; Linseman, D. Neuroprotective effects of anthocyanins on apoptosis induced by mitochondrial oxidative stress. Nutr. Neurosci., 2011, 14(6), 249-259.
[http://dx.doi.org/10.1179/1476830511Y.0000000020] [PMID: 22053756]
[99]
Pereira, R.M.; Andrades, N.E.; Paulino, N.; Sawaya, A.C.; Eberlin, M.N.; Marcucci, M.C.; Favero, G.M.; Novak, E.M.; Bydlowski, S.P. Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity. Molecules, 2007, 12(7), 1352-1366.
[http://dx.doi.org/10.3390/12071352] [PMID: 17909491]
[100]
Golechha, M.; Chaudhry, U.; Bhatia, J.; Saluja, D.; Arya, D.S. Naringin protects against kainic acid-induced status epilepticus in rats: evidence for an antioxidant, anti-inflammatory and neuroprotective intervention. Biol. Pharm. Bull., 2011, 34(3), 360-365.
[http://dx.doi.org/10.1248/bpb.34.360] [PMID: 21372385]
[101]
Kumar, P.; Kumar, A. Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington’s like symptoms in rats: possible role of nitric oxide. Behav. Brain Res., 2010c, 206(1), 38-46.
[http://dx.doi.org/10.1016/j.bbr.2009.08.028] [PMID: 19716383]
[102]
Kumar, A.; Dogra, S.; Prakash, A. Protective effect of naringin, a citrus flavonoid, against colchicine-induced cognitive dysfunction and oxidative damage in rats. J. Med. Food, 2010a, 13(4), 976-984.
[http://dx.doi.org/10.1089/jmf.2009.1251] [PMID: 20673063]
[103]
Wang, D.; Gao, K.; Li, X.; Shen, X.; Zhang, X.; Ma, C.; Qin, C.; Zhang, L. Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficits in a mouse model of Alzheimer’s disease. Pharmacol. Biochem. Behav., 2012, 102(1), 13-20.
[http://dx.doi.org/10.1016/j.pbb.2012.03.013] [PMID: 22741174]
[104]
Heo, H.J.; Kim, M.J.; Lee, J.M.; Choi, S.J.; Cho, H.Y.; Hong, B.; Kim, H.K.; Kim, E.; Shin, D.H. Naringenin from Citrus junos has an inhibitory effect on acetylcholinesterase and a mitigating effect on amnesia. Dement. Geriatr. Cogn. Disord., 2004b, 17(3), 151-157.
[http://dx.doi.org/10.1159/000076349] [PMID: 14739537]
[105]
Leem, E.; Nam, J.H.; Jeon, M.T.; Shin, W.H.; Won, S.Y.; Park, S.J.; Choi, M.S.; Jin, B.K.; Jung, U.J.; Kim, S.R. Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson’s disease. J. Nutr. Biochem., 2014, 25(7), 801-806.
[http://dx.doi.org/10.1016/j.jnutbio.2014.03.006] [PMID: 24797334]
[106]
Kim, H.J.; Song, J.Y.; Park, H.J.; Park, H.K.; Yun, D.H.; Chung, J.H. Naringin Protects against Rotenone-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells. Korean J. Physiol. Pharmacol., 2009, 13(4), 281-285.
[http://dx.doi.org/10.4196/kjpp.2009.13.4.281] [PMID: 19885011]
[107]
Sachdeva, A.K.; Chopra, K. Naringin mitigate okadaic acid-induced cognitive impairment in an experimental paradigm of Alzheimer’s disease. J. Funct. Foods, 2015, 19, 110-125.
[http://dx.doi.org/10.1016/j.jff.2015.08.024]
[108]
Chen, S.F.; Hsu, C.W.; Huang, W.H.; Wang, J.Y. Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury. Br. J. Pharmacol., 2008, 155(8), 1279-1296.
[http://dx.doi.org/10.1038/bjp.2008.345] [PMID: 18776918]
[109]
Lebeau, A.; Esclaire, F.; Rostène, W.; Pélaprat, D. Baicalein protects cortical neurons from beta-amyloid (25-35) induced toxicity. Neuroreport, 2001, 12(10), 2199-2202.
[http://dx.doi.org/10.1097/00001756-200107200-00031] [PMID: 11447334]
[110]
Lee, H-H.; Yang, L-L.; Wang, C-C.; Hu, S-Y.; Chang, S-F.; Lee, Y-H. Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate- and glucose deprivation-induced neuronal death. Brain Res., 2003, 986(1-2), 103-113.
[http://dx.doi.org/10.1016/S0006-8993(03)03197-4] [PMID: 12965234]
[111]
Kren, V.; Walterová, D. Silybin and silymarin--new effects and applications. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2005, 149(1), 29-41.
[http://dx.doi.org/10.5507/bp.2005.002] [PMID: 16170386]
[112]
Trouillas, P.; Marsal, P.; Svobodová, A.; Vostálová, J.; Gazák, R.; Hrbác, J.; Sedmera, P.; Kren, V.; Lazzaroni, R.; Duroux, J.L.; Walterová, D. Mechanism of the antioxidant action of silybin and 2,3-dehydrosilybin flavonolignans: a joint experimental and theoretical study. J. Phys. Chem. A, 2008, 112(5), 1054-1063.
[http://dx.doi.org/10.1021/jp075814h] [PMID: 18193843]
[113]
Lu, P.; Mamiya, T.; Lu, L.L.; Mouri, A.; Zou, L.; Nagai, T.; Hiramatsu, M.; Ikejima, T.; Nabeshima, T. Silibinin prevents amyloid beta peptide-induced memory impairment and oxidative stress in mice. Br. J. Pharmacol., 2009, 157(7), 1270-1277.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00295.x] [PMID: 19552690]
[114]
Kim, J.K.; Choi, S.J.; Cho, H.Y.; Hwang, H.J.; Kim, Y.J.; Lim, S.T.; Kim, C.J.; Kim, H.K.; Peterson, S.; Shin, D.H. Protective effects of kaempferol (3,4′,5,7-tetrahydroxyflavone) against amyloid β peptide (Abeta)-induced neurotoxicity in ICR mice. Biosci. Biotechnol. Biochem., 2010, 74(2), 397-401.
[http://dx.doi.org/10.1271/bbb.90585] [PMID: 20139605]
[115]
Lei, Y.; Chen, J.; Zhang, W.; Fu, W.; Wu, G.; Wei, H.; Wang, Q.; Ruan, J. In vivo investigation on the potential of galangin, kaempferol and myricetin for protection of D-galactose-induced cognitive impairment. Food Chem., 2012, 135(4), 2702-2707.
[http://dx.doi.org/10.1016/j.foodchem.2012.07.043] [PMID: 22980861]
[116]
Wang, L.; Andersson, S.; Warner, M.; Gustafsson, J.A. Morphological abnormalities in the brains of estrogen receptor beta knockout mice. Proc. Natl. Acad. Sci. USA, 2001, 98(5), 2792-2796.
[http://dx.doi.org/10.1073/pnas.041617498] [PMID: 11226319]
[117]
Menze, E.T.; Esmat, A.; Tadros, M.G.; Abdel-Naim, A.B.; Khalifa, A.E. Genistein improves 3-NPA-induced memory impairment in ovariectomized rats: impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties. PLoS One, 2015, 10(2), e0117223.
[http://dx.doi.org/10.1371/journal.pone.0117223] [PMID: 25675218]
[118]
Bagheri, M.; Joghataei, M.T.; Mohseni, S.; Roghani, M. Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer’s disease. Neurobiol. Learn. Mem., 2011, 95(3), 270-276.
[http://dx.doi.org/10.1016/j.nlm.2010.12.001] [PMID: 21144907]
[119]
Heo, J.H.; Lee, S.T.; Chu, K.; Oh, M.J.; Park, H.J.; Shim, J.Y.; Kim, M. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer’s disease. Eur. J. Neurol., 2008, 15(8), 865-868.
[http://dx.doi.org/10.1111/j.1468-1331.2008.02157.x] [PMID: 18684311]
[120]
Hou, Y.C.; Chao, P.D.; Chen, S.Y. Honokiol and magnolol increased hippocampal acetylcholine release in freely-moving rats. Am. J. Chin. Med., 2000, 28(3-4), 379-384.
[http://dx.doi.org/10.1142/S0192415X00000441] [PMID: 11154051]
[121]
Lo, Y.C.; Teng, C.M.; Chen, C.F.; Chen, C.C.; Hong, C.Y. Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation. Biochem. Pharmacol., 1994, 47(3), 549-553.
[http://dx.doi.org/10.1016/0006-2952(94)90187-2] [PMID: 8117323]
[122]
Wang, J.P.; Hsu, M.F.; Raung, S.L.; Chen, C.C.; Kuo, J.S.; Teng, C.M. Anti-inflammatory and analgesic effects of magnolol. Naunyn Schmiedebergs Arch. Pharmacol., 1992, 346(6), 707-712.
[http://dx.doi.org/10.1007/BF00168746] [PMID: 1336574]
[123]
Caterina, M.J.; Schumacher, M.A.; Tominaga, M.; Rosen, T.A.; Levine, J.D.; Julius, D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 1997, 389(6653), 816-824.
[http://dx.doi.org/10.1038/39807] [PMID: 9349813]
[124]
Kauer, J.A.; Gibson, H.E. Hot flash: TRPV channels in the brain. Trends Neurosci., 2009, 32(4), 215-224.
[http://dx.doi.org/10.1016/j.tins.2008.12.006] [PMID: 19285736]
[125]
Jiang, X.; Jia, L.W.; Li, X.H.; Cheng, X.S.; Xie, J.Z.; Ma, Z.W.; Xu, W.J.; Liu, Y.; Yao, Y.; Du, L.L.; Zhou, X.W. Capsaicin ameliorates stress-induced Alzheimer’s disease-like pathological and cognitive impairments in rats. J. Alzheimers Dis., 2013, 35(1), 91-105.
[http://dx.doi.org/10.3233/JAD-121837] [PMID: 23340038]
[126]
Witte, A.V.; Kerti, L.; Margulies, D.S.; Flöel, A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J. Neurosci., 2014, 34(23), 7862-7870.
[http://dx.doi.org/10.1523/JNEUROSCI.0385-14.2014] [PMID: 24899709]

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