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Central Nervous System Agents in Medicinal Chemistry

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ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

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Mini-Review Article

Resveratrol: Protective Agent Against Alzheimer’s Disease

Author(s): Iqra Subhan and Yasir Hasan Siddique*

Volume 24, Issue 3, 2024

Published on: 11 March, 2024

Page: [249 - 263] Pages: 15

DOI: 10.2174/0118715249287167240222081517

Price: $65

Abstract

Resveratrol is a biologically active natural phenolic plant product. It has several properties which make them useful to treat the disease. In this review, we have highlighted the neuroprotective effects of resveratrol. Several available animal models have been proven to help understand the disease pathway and mechanism of action by resveratrol. In this review, we have highlighted the neuroprotective activity of resveratrol in AD, which effectively counter the neurodegenerative disease by decreasing the formation of plaques.

Resveratrol is a natural plant product that is easily available, cost-effective, and possesses neuroprotective activity, which is useful for treating neurodegenerative diseases. Resveratrol presents a promising avenue for AD treatment due to its diverse neuroprotective mechanisms. Given the ongoing global challenge in treating AD, researchers have increasingly focused on exploring the therapeutic potential of resveratrol.

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[1]
Bhat, K.P.L.; Kosmeder, J.W., II; Pezzuto, J.M. Biological effects of resveratrol. Antioxid. Redox Signal., 2001, 3(6), 1041-1064.
[http://dx.doi.org/10.1089/152308601317203567] [PMID: 11813979]
[2]
Baur, J.A.; Sinclair, D.A. Therapeutic potential of resveratrol: The in vivo evidence. Nat. Rev. Drug Discov., 2006, 5(6), 493-506.
[http://dx.doi.org/10.1038/nrd2060] [PMID: 16732220]
[3]
King, R.E.; Bomser, J.A.; Min, D.B. Bioactivity of resveratrol. Compr. Rev. Food Sci. Food Saf., 2006, 5(3), 65-70.
[http://dx.doi.org/10.1111/j.1541-4337.2006.00001.x]
[4]
Sun, A.Y.; Wang, Q.; Simonyi, A.; Sun, G.Y. Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol. Neurobiol., 2010, 41(2-3), 375-383.
[http://dx.doi.org/10.1007/s12035-010-8111-y] [PMID: 20306310]
[5]
Tellone, E.; Galtieri, A.; Russo, A.; Giardina, B.; Ficarra, S. Resveratrol: A focus on several neurodegenerative diseases. Oxid. Med. Cell. Longev., 2015, 2015, 1-14.
[http://dx.doi.org/10.1155/2015/392169] [PMID: 26180587]
[6]
González, R.H.I.; Tututi, A.M.; Soto, G.V. Resveratrol: A natural compound with pharmacological potential in neurodegenerative diseases. CNS Neurosci. Ther., 2008, 14(3), 234-247.
[http://dx.doi.org/10.1111/j.1755-5949.2008.00045.x] [PMID: 18684235]
[7]
Pallàs, M.; Casadesús, G.; Smith, M.; Montes, C.A.; Pelegri, C.; Vilaplana, J.; Camins, A. Resveratrol and neurodegenerative diseases: Activation of SIRT1 as the potential pathway towards neuroprotection. Curr. Neurovasc. Res., 2009, 6(1), 70-81.
[http://dx.doi.org/10.2174/156720209787466019] [PMID: 19355928]
[8]
Komorowska, J.; Wątroba, M.; Szukiewicz, D. Review of beneficial effects of resveratrol in neurodegenerative diseases such as Alzheimer’s disease. Adv. Med. Sci., 2020, 65(2), 415-423.
[http://dx.doi.org/10.1016/j.advms.2020.08.002] [PMID: 32871321]
[9]
Huang, J.; Huang, N.; Xu, S.; Luo, Y.; Li, Y.; Jin, H.; Yu, C.; Shi, J.; Jin, F. Signaling mechanisms underlying inhibition of neuroinflammation by resveratrol in neurodegenerative diseases. J. Nutr. Biochem., 2021, 88, 108552.
[http://dx.doi.org/10.1016/j.jnutbio.2020.108552] [PMID: 33220405]
[10]
Ali, F.; Rahul; Jyoti, S.; Naz, F.; Ashafaq, M.; Shahid, M.; Siddique, Y.H. Therapeutic potential of luteolin in transgenic Drosophila model of Alzheimer’s disease. Neurosci. Lett., 2019, 692, 90-99.
[http://dx.doi.org/10.1016/j.neulet.2018.10.053] [PMID: 30420334]
[11]
Siddique, Y.H.; Rahul; Ara, G.; Afzal, M.; Varshney, H.; Gaur, K.; Subhan, I.; Mantasha, I.; Shahid, M. Beneficial effects of apigenin on the transgenic Drosophila model of Alzheimer’s disease. Chem. Biol. Interact., 2022, 366, 110120.
[http://dx.doi.org/10.1016/j.cbi.2022.110120] [PMID: 36027948]
[12]
Kim, M.; Jung, J.; Jeong, N.Y.; Chung, H.J. The natural plant flavonoid apigenin is a strong antioxidant that effectively delays peripheral neurodegenerative processes. Anat. Sci. Int., 2019, 94(4), 285-294.
[http://dx.doi.org/10.1007/s12565-019-00486-2] [PMID: 30949912]
[13]
Siddique, Y.H.; Naz, F.; Jyoti, S. Effect of curcumin on lifespan, activity pattern, oxidative stress, and apoptosis in the brains of transgenic Drosophila model of Parkinson’s disease. BioMed Res. Int., 2014, 2014, 1-6.
[http://dx.doi.org/10.1155/2014/606928] [PMID: 24860828]
[14]
Bayazid, A.B.; Lim, B.O. Quercetin is an active agent in berries against neurodegenerative diseases progression through modulation of Nrf2/HO1. Nutrients, 2022, 14(23), 5132.
[http://dx.doi.org/10.3390/nu14235132] [PMID: 36501161]
[15]
Naz, F.; Jyoti, S.; Siddique, Y.H. Effect of kaempferol on the transgenic Drosophila model of Parkinson’s disease. Sci. Rep., 2020, 10(1), 1-14.
[PMID: 31913322]
[16]
Siddique, Y.H.; Naz, F.; Jyoti, S.; Ali, F.; Rahul Effect of genistein on the transgenic Drosophila model of Parkinson’s Disease. J. Diet. Suppl., 2019, 16(5), 550-563.
[http://dx.doi.org/10.1080/19390211.2018.1472706] [PMID: 29969325]
[17]
Nejabati, H.R.; Roshangar, L. Kaempferol as a potential neuroprotector in Alzheimer’s disease. J. Food Biochem., 2022, 46(12), e14375.
[http://dx.doi.org/10.1111/jfbc.14375] [PMID: 35929364]
[18]
Hasan Siddique, Y.; Rahul; Varshney, H.; Mantasha, I.; Shahid, M. Effect of luteolin on the transgenic Drosophila model of Huntington’s disease. Comput. Toxicol., 2021, 17, 100148.
[http://dx.doi.org/10.1016/j.comtox.2020.100148]
[19]
Siddique, Y.H.; Naz, F.; Jyoti, S.; Ali, F.; Fatima, A.; Rahul; Khanam, S. Protective effect of geraniol on the transgenic Drosophila model of parkinson’s disease. Environ. Toxicol. Pharmacol., 2016, 43, 225-231.
[http://dx.doi.org/10.1016/j.etap.2016.03.018] [PMID: 27026137]
[20]
Gerszon, J.; Rodacka, A.; Puchała, M. Antioxidant properties of resveratrol and its protective effects in neurodegenerative diseases. Adv. Cell Biol., 2014, 4(2), 97-117.
[http://dx.doi.org/10.2478/acb-2014-0006]
[21]
Foti Cuzzola, V.; Ciurleo, R.; Giacoppo, S.; Marino, S.; Bramanti, P. Role of resveratrol and its analogues in the treatment of neurodegenerative diseases: focus on recent discoveries. CNS Neurol. Disord. Drug Targets, 2011, 10(7), 849-862.
[http://dx.doi.org/10.2174/187152711798072310] [PMID: 21999735]
[22]
Timmers, S.; Auwerx, J.; Schrauwen, P. The journey of resveratrol from yeast to human. Aging, 2012, 4(3), 146-158.
[http://dx.doi.org/10.18632/aging.100445] [PMID: 22436213]
[23]
Burns, J.; Yokota, T.; Ashihara, H.; Lean, M.E.J.; Crozier, A.; Agric, J. Plant foods and herbal sources of resveratrol. J. Agric. Food Chem., 2002, 50(11), 3337-3340.
[http://dx.doi.org/10.1021/jf0112973] [PMID: 12010007]
[24]
Ponzo, V.; Soldati, L.; Bo, S. Resveratrol: A supplementation for men or for mice? J. Transl. Med., 2014, 12(1), 158.
[http://dx.doi.org/10.1186/1479-5876-12-158] [PMID: 24893845]
[25]
Berman, A.Y.; Motechin, R.A.; Wiesenfeld, M.Y.; Holz, M.K. The therapeutic potential of resveratrol: A review of clinical trials. NPJ Precis. Oncol., 2017, 1(1), 35.
[http://dx.doi.org/10.1038/s41698-017-0038-6] [PMID: 28989978]
[26]
Amri, A.; Chaumeil, J.C.; Sfar, S.; Charrueau, C. Administration of resveratrol: What formulation solutions to bioavailability limitations? J. Control. Release, 2012, 158(2), 182-193.
[http://dx.doi.org/10.1016/j.jconrel.2011.09.083] [PMID: 21978644]
[27]
Walle, T. Bioavailability of resveratrol. Ann. N. Y. Acad. Sci., 2011, 1215(1), 9-15.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05842.x] [PMID: 21261636]
[28]
Giacomini, E.; Rupiani, S.; Guidotti, L.; Recanatini, M.; Roberti, M. The use of stilbene scaffold in medicinal chemistry and multi-target drug design. Curr Med Chem, 2016, 23, 2439e2489.
[http://dx.doi.org/10.2174/0929867323666160517121629]
[29]
Wang, P.; Sang, S. Metabolism and pharmacokinetics of resveratrol and pterostilbene. Biofactors, 2018, 44(1), 16-25.
[http://dx.doi.org/10.1002/biof.1410] [PMID: 29315886]
[30]
Yu, C.; Shin, Y.G.; Chow, A.; Li, Y.; Kosmeder, J.W.; Lee, Y.S.; Hirschelman, W.H.; Pezzuto, J.M.; Mehta, R.G.; van Breemen, R.B. Human, rat, and mouse metabolism of resveratrol. Pharm. Res., 2002, 19(12), 1907-1914.
[http://dx.doi.org/10.1023/A:1021414129280] [PMID: 12523673]
[31]
Calabrese, E.J.; Mattson, M.P.; Calabrese, V. Resveratrol commonly displays hormesis: Occurrence and biomedical significance. Hum. Exp. Toxicol., 2010, 29(12), 980-1015.
[http://dx.doi.org/10.1177/0960327110383625] [PMID: 21115559]
[32]
Zhao, H.F.; Li, N.; Wang, Q.; Cheng, X.J.; Li, X.M.; Liu, T.T. Resveratrol decreases the insoluble Aβ1–42 level in hippocampus and protects the integrity of the blood–brain barrier in AD rats. Neuroscience, 2015, 310, 641-649.
[http://dx.doi.org/10.1016/j.neuroscience.2015.10.006] [PMID: 26454022]
[33]
Ahmed, T.; Javed, S.; Javed, S.; Tariq, A.; Šamec, D.; Tejada, S.; Nabavi, S.F.; Braidy, N.; Nabavi, S.M. Resveratrol and Alzheimer’s disease: Mechanistic insights. Mol. Neurobiol., 2017, 54(4), 2622-2635.
[http://dx.doi.org/10.1007/s12035-016-9839-9] [PMID: 26993301]
[34]
Richard, T.; Pawlus, A.D.; Iglésias, M.L.; Pedrot, E.; Teguo, W.P.; Mérillon, J.M.; Monti, J.P. Neuroprotective properties of resveratrol and derivatives. Ann. N. Y. Acad. Sci., 2011, 1215(1), 103-108.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05865.x] [PMID: 21261647]
[35]
Karuppagounder, S.S.; Pinto, J.T.; Xu, H.; Chen, H.L.; Beal, M.F.; Gibson, G.E. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem. Int., 2009, 54(2), 111-118.
[http://dx.doi.org/10.1016/j.neuint.2008.10.008] [PMID: 19041676]
[36]
Zhang, Y.; Li, Y.; Wang, Y.; Wang, G.; Mao, L.; Zhang, D.; Wang, J. Effects of resveratrol on learning and memory in rats with vascular dementia. Mol. Med. Rep., 2019, 20(5), 4587-4593.
[http://dx.doi.org/10.3892/mmr.2019.10723] [PMID: 31702039]
[37]
Camins, A.; Pelegri, C.; Vilaplana, J.; Cristofol, R.; Sanfeliu, C.; Pallàs, M. 22 sirtuin and resveratrol. In: Micronutrients and Brain Health; Superior Council of Scientific Investigations, 2009; p. 329.
[38]
Galiniak, S.; Aebisher, D.; Aebisher, B.D. Health benefits of resveratrol administration. Acta Biochim. Pol., 2019, 66(1), 13-21.
[PMID: 30816367]
[39]
Franciosoa, A.; Mastromarino, P.; Masci, A.; d’Erme, M.; Mosca, L. Chemistry, stability and bioavailability of resveratrol. Med. Chem., 2014, 10(3), 237-245.
[http://dx.doi.org/10.2174/15734064113096660053] [PMID: 24329932]
[40]
Frémont, L. Biological effects of resveratrol. Life Sci., 2000, 66(8), 663-673.
[http://dx.doi.org/10.1016/S0024-3205(99)00410-5] [PMID: 10680575]
[41]
Gresele, P.; Cerletti, C.; Guglielmini, G.; Pignatelli, P.; de Gaetano, G.; Violi, F. Effects of resveratrol and other wine polyphenols on vascular function: An update. J. Nutr. Biochem., 2011, 22(3), 201-211.
[http://dx.doi.org/10.1016/j.jnutbio.2010.07.004] [PMID: 21111592]
[42]
Gambini, J.; Inglés, M.; Olaso, G.; Grueso, L.R.; Costa, B.V.; Mallench, G.L.; Bargues, M.C.; Abdelaziz, K.M.; Cabrera, G.M.C.; Vina, J.; Borras, C. Properties of resveratrol: In vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. In: Oxid. Med. Cell. Longev; , 2015; 2015, p. 837042.
[43]
Li, F.; Gong, Q.; Dong, H.; Shi, J. Resveratrol, a neuroprotective supplement for Alzheimer’s disease. Curr. Pharm. Des., 2012, 18(1), 27-33.
[http://dx.doi.org/10.2174/138161212798919075] [PMID: 22211686]
[44]
Kou, X.; Chen, N. Resveratrol as a natural autophagy regulator for prevention and treatment of Alzheimer’s disease. Nutrients, 2017, 9(9), 927.
[http://dx.doi.org/10.3390/nu9090927] [PMID: 28837083]
[45]
Jin, F.; Wu, Q.; Lu, Y.F.; Gong, Q.H.; Shi, J.S. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur. J. Pharmacol., 2008, 600(1-3), 78-82.
[http://dx.doi.org/10.1016/j.ejphar.2008.10.005] [PMID: 18940189]
[46]
Rege, S.D.; Geetha, T.; Griffin, G.D.; Broderick, T.L.; Babu, J.R. Neuroprotective effects of resveratrol in Alzheimer disease pathology. Front. Aging Neurosci., 2014, 6, 218.
[http://dx.doi.org/10.3389/fnagi.2014.00218] [PMID: 25309423]
[47]
Griñán-Ferré, C.; Bellver-Sanchis, A.; Izquierdo, V.; Corpas, R.; Roig-Soriano, J.; Chillón, M.; Lacueva, A.C.; Somogyvári, M.; Sőti, C.; Sanfeliu, C.; Pallàs, M. The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer’s disease pathology: From antioxidant to epigenetic therapy. Ageing Res. Rev., 2021, 67, 101271.
[http://dx.doi.org/10.1016/j.arr.2021.101271] [PMID: 33571701]
[48]
Albani, D.; Polito, L.; Signorini, A.; Forloni, G. Neuroprotective properties of resveratrol in different neurodegenerative disorders. Biofactors, 2010, 36(5), 370-376.
[http://dx.doi.org/10.1002/biof.118] [PMID: 20848560]
[49]
Yuan, S.F.; Yi, X.; Johnston, T.G.; Alper, H.S. De novo resveratrol production through modular engineering of an Escherichia coli–Saccharomyces cerevisiae co-culture. Microb. Cell Fact., 2020, 19(1), 143.
[http://dx.doi.org/10.1186/s12934-020-01401-5] [PMID: 32664999]
[50]
Gomes, B.A.Q.; Silva, J.P.B.; Romeiro, C.F.R.; dos Santos, S.M.; Rodrigues, C.A.; Gonçalves, P.R.; Sakai, J.T.; Mendes, P.F.S.; Varela, E.L.P.; Monteiro, M.C. Neuroprotective mechanisms of resveratrol in Alzheimer’s disease: Role of SIRT1. Oxid. Med. Cell. Longev., 2018, 2018, 1-15.
[http://dx.doi.org/10.1155/2018/8152373] [PMID: 30510627]
[51]
Siddique, Y.H.; Naz, F.; Rahul, .; Varshney, H. Comparative study of rivastigmine and galantamine on the transgenic Drosophila model of Alzheimer’s disease. Current Research in Pharmacology and Drug Discovery, 2022, 3, 100120.
[http://dx.doi.org/10.1016/j.crphar.2022.100120] [PMID: 35992376]
[52]
Varshney, H.; Siddique, Y.H. Role of natural plant products against Alzheimer’s disease. CNS Neurol. Disord. Drug Targets, 2021, 20(10), 904-941.
[53]
Rahman, M.H.; Akter, R.; Bhattacharya, T.; Daim, A.M.M.; Alkahtani, S.; Arafah, M.W.; Al-Johani, N.S.; Alhoshani, N.M.; Alkeraishan, N.; Alhenaky, A.; Abd-Elkader, O.H.; El-Seedi, H.R.; Kaushik, D.; Mittal, V. Resveratrol and neuroprotection: impact and its therapeutic potential in Alzheimer’s disease. Front. Pharmacol., 2020, 11, 619024.
[http://dx.doi.org/10.3389/fphar.2020.619024] [PMID: 33456444]
[54]
Ballard, C.; Gauthier, S.; Corbett, A.; Brayne, C.; Aarsland, D.; Jones, E. Alzheimer’s disease. Lancet, 2011, 377(9770), 1019-1031.
[http://dx.doi.org/10.1016/S0140-6736(10)61349-9] [PMID: 21371747]
[55]
Scheltens, P.; De Strooper, B.; Kivipelto, M.; Holstege, H.; Chételat, G.; Teunissen, C.E.; Cummings, J.; van der Flier, W.M. Alzheimer’s disease. Lancet, 2021, 397(10284), 1577-1590.
[http://dx.doi.org/10.1016/S0140-6736(20)32205-4] [PMID: 33667416]
[56]
Siddique, Y.H.; Naz, F.; Rahul; Rashid, M.; Tajuddin Effect of majun baladur on life span, climbing ability, oxidative stress and dopaminergic neurons in the transgenic Drosophila model of Parkinson’s disease. Heliyon, 2019, 5(4), e01483.
[http://dx.doi.org/10.1016/j.heliyon.2019.e01483] [PMID: 31011645]
[57]
Bagyinszky, E.; Youn, Y.C.; An, S.; Kim, S. The genetics of Alzheimer’s disease. Clin. Interv. Aging, 2014, 9, 535-551.
[http://dx.doi.org/10.2147/CIA.S51571] [PMID: 24729694]
[58]
Pasinetti, G.M.; Wang, J.; Marambaud, P.; Ferruzzi, M.; Gregor, P.; Knable, L.A.; Ho, L. Neuroprotective and metabolic effects of resveratrol: Therapeutic implications for Huntington’s disease and other neurodegenerative disorders. Exp. Neurol., 2011, 232(1), 1-6.
[http://dx.doi.org/10.1016/j.expneurol.2011.08.014] [PMID: 21907197]
[59]
Ma, X.; Sun, Z.; Han, X.; Li, S.; Jiang, X.; Chen, S.; Zhang, J.; Lu, H. Neuroprotective effect of resveratrol via activation of Sirt1 signaling in a rat model of combined diabetes and Alzheimer’s disease. Front. Neurosci., 2020, 13, 1400.
[http://dx.doi.org/10.3389/fnins.2019.01400] [PMID: 32038127]
[60]
Rosa, P.M.; Martins, L.A.M.; Souza, D.O.; Santos, Q.A. Glioprotective effect of resveratrol: An emerging therapeutic role for oligodendroglial cells. Mol. Neurobiol., 2018, 55(4), 2967-2978.
[http://dx.doi.org/10.1007/s12035-017-0510-x] [PMID: 28456938]
[61]
Bondi, M.W.; Edmonds, E.C.; Salmon, D.P. Alzheimer’s disease: Past, present, and future. J. Int. Neuropsychol. Soc., 2017, 23(9-10), 818-831.
[http://dx.doi.org/10.1017/S135561771700100X] [PMID: 29198280]
[62]
Brion, J.P. Neurofibrillary tangles and Alzheimer’s disease. Eur. Neurol., 1998, 40(3), 130-140.
[http://dx.doi.org/10.1159/000007969] [PMID: 9748670]
[63]
Heneka, M.; Obanion, M. Inflammatory processes in Alzheimer’s disease. J. Neuroimmunol., 2007, 184(1-2), 69-91.
[http://dx.doi.org/10.1016/j.jneuroim.2006.11.017] [PMID: 17222916]
[64]
Finder, V.H. Alzheimer’s disease: A general introduction and pathomechanism. J. Alzheimers Dis., 2010, 22(S3), S5-S19.
[http://dx.doi.org/10.3233/JAD-2010-100975] [PMID: 20858960]
[65]
De-Paula, V.J.; Radanovic, M.; Diniz, B.S.; Forlenza, O.V. Alzheimer’s disease. Subcell. Biochem., 2012, 65, 329-352.
[http://dx.doi.org/10.1007/978-94-007-5416-4_14] [PMID: 23225010]
[66]
Bolós, M.; Perea, J.R.; Avila, J. Alzheimer’s disease as an inflammatory disease. Biomol. Concepts, 2017, 8(1), 37-43.
[http://dx.doi.org/10.1515/bmc-2016-0029] [PMID: 28231054]
[67]
DiSabato, D.J.; Quan, N.; Godbout, J.P. Neuroinflammation: the devil is in the details. J. Neurochem., 2016, 139(S2), 136-153.
[http://dx.doi.org/10.1111/jnc.13607] [PMID: 26990767]
[68]
Karpińska, A.; Gromadzka, G. Oxidative stress and natural antioxidant mechanisms: The role in neurodegeneration. From molecular mechanisms to therapeutic strategies. Postepy Hig. Med. Dosw., 2013, 67, 43-53.
[http://dx.doi.org/10.5604/17322693.1029530] [PMID: 23475482]
[69]
Huang, W.J.; Zhang, X.; Chen, W.W. Role of oxidative stress in Alzheimer’s disease. Biomed. Rep., 2016, 4(5), 519-522.
[http://dx.doi.org/10.3892/br.2016.630] [PMID: 27123241]
[70]
Förstl, H.; Kurz, A. Clinical features of Alzheimer’s disease. Eur. Arch. Psychiatry Clin. Neurosci., 1999, 249(6), 288-290.
[http://dx.doi.org/10.1007/s004060050101] [PMID: 10653284]
[71]
Sawda, C.; Moussa, C.; Turner, R.S. Resveratrol for Alzheimer’s disease. Ann. N. Y. Acad. Sci., 2017, 1403(1), 142-149.
[http://dx.doi.org/10.1111/nyas.13431] [PMID: 28815614]
[72]
Turner, R.S.; Thomas, R.G.; Craft, S.; van Dyck, C.H.; Mintzer, J.; Reynolds, B.A.; Brewer, J.B.; Rissman, R.A.; Raman, R.; Aisen, P.S.; Mintzer, J.; Reynolds, B.A.; Karlawish, J.; Galasko, D.; Heidebrink, J.; Aggarwal, N.; Radford, G.N.; Sano, M.; Petersen, R.; Bell, K.; Doody, R.; Smith, A.; Bernick, C.; Porteinsson, A.; Tariot, P.; Mulnard, R.; Lerner, A.; Schneider, L.; Burns, J.; Raskind, M.; Ferris, S.; Jicha, G.; Quiceno, M.; Obisesan, T.; Rosenberg, P.; Weintraub, D.; Kieburtz, K.; Miller, B.; Kryscio, R.; Alexopoulis, G. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology, 2015, 85(16), 1383-1391.
[http://dx.doi.org/10.1212/WNL.0000000000002035] [PMID: 26362286]
[73]
Zhao, Y.N.; Li, W.F.; Li, F.; Zhang, Z.; Dai, Y.D.; Xu, A.L.; Qi, C.; Gao, J.M.; Gao, J. Resveratrol improves learning and memory in normally aged mice through microRNA-CREB pathway. Biochem. Biophys. Res. Commun., 2013, 435(4), 597-602.
[http://dx.doi.org/10.1016/j.bbrc.2013.05.025] [PMID: 23685142]
[74]
Lagos-Quintana, M.; Rauhut, R.; Yalcin, A.; Meyer, J.; Lendeckel, W.; Tuschl, T. Identification of tissue-specific microRNAs from mouse. Curr. Biol., 2002, 12(9), 735-739.
[http://dx.doi.org/10.1016/S0960-9822(02)00809-6] [PMID: 12007417]
[75]
Rajasethupathy, P.; Fiumara, F.; Sheridan, R.; Betel, D.; Puthanveettil, S.V.; Russo, J.J.; Sander, C.; Tuschl, T.; Kandel, E. Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB. Neuron, 2009, 63(6), 803-817.
[http://dx.doi.org/10.1016/j.neuron.2009.05.029] [PMID: 19778509]
[76]
Chen, Z.J.; Yang, Y.F.; Zhang, Y.T.; Yang, D.H. Dietary total prenylflavonoids from the fruits of Psoralea corylifolia L. prevents age-related cognitive deficits and down-regulates Alzheimer’s markers in SAMP8 mice. Molecules, 2018, 23(1), 196.
[77]
Kumar, R.; Nigam, L.; Singh, A.P.; Singh, K.; Subbarao, N.; Dey, S. Design, synthesis of allosteric peptide activator for human SIRT1 and its biological evaluation in cellular model of Alzheimer’s disease. Eur. J. Med. Chem., 2017, 127, 909-916.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.001] [PMID: 27836195]
[78]
Marwarha, G.; Raza, S.; Meiers, C.; Ghribi, O. Leptin attenuates BACE1 expression and amyloid-β genesis via the activation of SIRT1 signaling pathway. Biochim. Biophys. Acta Mol. Basis Dis., 2014, 1842(9), 1587-1595.
[http://dx.doi.org/10.1016/j.bbadis.2014.05.015] [PMID: 24874077]
[79]
Koo, J.H.; Kang, E.B.; Oh, Y.S.; Yang, D.S.; Cho, J.Y. Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer’s disease. Exp. Neurol., 2017, 288, 142-152.
[http://dx.doi.org/10.1016/j.expneurol.2016.11.014] [PMID: 27889467]
[80]
Huang, T.C.; Lu, K.T.; Wo, Y.Y.P.; Wu, Y.J.; Yang, Y.L. Resveratrol protects rats from Aβ-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation. PLoS One, 2011, 6(12), e29102.
[http://dx.doi.org/10.1371/journal.pone.0029102] [PMID: 22220203]
[81]
Chen, J.; Zhou, Y.; Mueller-Steiner, S.; Chen, L.F.; Kwon, H.; Yi, S.; Mucke, L.; Gan, L. SIRT1 protects against microglia-dependent amyloid-β toxicity through inhibiting NF-kappaB signaling. J. Biol. Chem., 2005, 280(48), 40364-40374.
[http://dx.doi.org/10.1074/jbc.M509329200] [PMID: 16183991]
[82]
Anekonda, T.S. Resveratrol—A boon for treating Alzheimer’s disease? Brain Res. Brain Res. Rev., 2006, 52(2), 316-326.
[http://dx.doi.org/10.1016/j.brainresrev.2006.04.004] [PMID: 16766037]
[83]
Kumar, A.; Naidu, P.S.; Seghal, N.; Padi, S.S.V. Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. Pharmacology, 2007, 79(1), 17-26.
[http://dx.doi.org/10.1159/000097511] [PMID: 17135773]
[84]
Gan, L.; Han, Y.; Bastianetto, S.; Dumont, Y.; Unterman, T.G.; Quirion, R. FoxO-dependent and -independent mechanisms mediate SirT1 effects on IGFBP-1 gene expression. Biochem. Biophys. Res. Commun., 2005, 337(4), 1092-1096.
[http://dx.doi.org/10.1016/j.bbrc.2005.09.169] [PMID: 16236254]
[85]
Guix, F.X.; Uribesalgo, I.; Coma, M.; Muñoz, F.J. The physiology and pathophysiology of nitric oxide in the brain. Prog. Neurobiol., 2005, 76(2), 126-152.
[http://dx.doi.org/10.1016/j.pneurobio.2005.06.001] [PMID: 16115721]
[86]
Wallerath, T.; Li, H.; Ambrust, G.U.; Schwarz, P.M.; Förstermann, U. A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide, 2005, 12(2), 97-104.
[http://dx.doi.org/10.1016/j.niox.2004.12.004] [PMID: 15740983]
[87]
Wang, J.; Fivecoat, H.; Ho, L.; Pan, Y.; Ling, E.; Pasinetti, G.M. The role of Sirt1: At the crossroad between promotion of longevity and protection against Alzheimer’s disease neuropathology. Biochim. Biophys. Acta. Proteins Proteomics, 2010, 1804(8), 1690-1694.
[http://dx.doi.org/10.1016/j.bbapap.2009.11.015] [PMID: 19945548]
[88]
Hardy, J.; Bogdanovic, N.; Winblad, B.; Portelius, E.; Andreasen, N.; Minguez, C.A.; Zetterberg, H. Pathways to Alzheimer’s disease. J. Intern. Med., 2014, 275(3), 296-303.
[http://dx.doi.org/10.1111/joim.12192] [PMID: 24749173]
[89]
Jahn, H. Memory loss in Alzheimer’s disease. Dialogues Clin. Neurosci., 2022, 15(4), 445-454.
[PMID: 24459411]
[90]
Carrizzo, A.; Puca, A.; Damato, A.; Marino, M.; Franco, E.; Pompeo, F.; Traficante, A.; Civitillo, F.; Santini, L.; Trimarco, V.; Vecchione, C. Resveratrol improves vascular function in patients with hypertension and dyslipidemia by modulating NO metabolism. Hypertension, 2013, 62(2), 359-366.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.01009] [PMID: 23753407]
[91]
Guerreiro, R.; Hardy, J. Genetics of Alzheimer’s disease. Neurotherapeutics, 2014, 11(4), 732-737.
[http://dx.doi.org/10.1007/s13311-014-0295-9] [PMID: 25113539]
[92]
Kim, Y.H.; Kim, Y.S.; Kang, S.S.; Cho, G.J.; Choi, W.S. Resveratrol inhibits neuronal apoptosis and elevated Ca2+/calmodulin-dependent protein kinase II activity in diabetic mouse retina. Diabetes, 2010, 59(7), 1825-1835.
[http://dx.doi.org/10.2337/db09-1431] [PMID: 20424226]
[93]
Rege, S.; Geetha, T.; Broderick, T.; Babu, J. Resveratrol protects β amyloid-induced oxidative damage and memory associated proteins in H19-7 hippocampal neuronal cells. Curr. Alzheimer Res., 2015, 12(2), 147-156.
[http://dx.doi.org/10.2174/1567205012666150204130009] [PMID: 25654502]
[94]
Price, D.L. New perspectives on Alzheimer’s disease. Annu. Rev. Neurosci., 1986, 9(1), 489-512.
[http://dx.doi.org/10.1146/annurev.ne.09.030186.002421] [PMID: 3518588]
[95]
Tomàs, C.M.; Senserrich, J.; Planas, A.M.; Alquézar, C.; Pallàs, M.; Requero, M.Á.; Suñol, C.; Kaliman, P.; Sanfeliu, C. Role of resveratrol and selenium on oxidative stress and expression of antioxidant and anti-aging genes in immortalized lymphocytes from Alzheimer’s disease patients. Nutrients, 2019, 11(8), 1764.
[http://dx.doi.org/10.3390/nu11081764] [PMID: 31370365]
[96]
Wang, X.; Ma, S.; Yang, B.; Huang, T.; Meng, N.; Xu, L.; Xing, Q.; Zhang, Y.; Zhang, K.; Li, Q.; Zhang, T.; Wu, J.; Yang, G.L.; Guan, F.; Wang, J. Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease. Behav. Brain Res., 2018, 339, 297-304.
[http://dx.doi.org/10.1016/j.bbr.2017.10.032] [PMID: 29102593]
[97]
Qi, Y.; Shang, L.; Liao, Z.; Su, H.; Jing, H.; Wu, B.; Bi, K.; Jia, Y. Intracerebroventricular injection of resveratrol ameliorated Aβ-induced learning and cognitive decline in mice. Metab. Brain Dis., 2019, 34(1), 257-266.
[http://dx.doi.org/10.1007/s11011-018-0348-6] [PMID: 30460524]
[98]
Cruz, N.A.R.; Ayala, R.Y.R.; Velasco, O.C.; Brambila, E.; Sosa, A.R.; Fernández, P.S.; Medina, M.J.C.; Alonso, A.P. Effect of chronic administration of resveratrol on cognitive performance during aging process in rats. Oxid. Med. Cell. Longev., 2017, 2017, 1-8.
[http://dx.doi.org/10.1155/2017/8510761] [PMID: 29163756]
[99]
Porquet, D.; Griñán-Ferré, C.; Ferrer, I.; Camins, A.; Sanfeliu, C.; del Valle, J.; Pallàs, M. Neuroprotective role of trans-resveratrol in a murine model of familial Alzheimer’s disease. J. Alzheimers Dis., 2014, 42(4), 1209-1220.
[http://dx.doi.org/10.3233/JAD-140444] [PMID: 25024312]
[100]
Gu, J.; Li, Z.; Chen, H.; Xu, X.; Li, Y.; Gui, Y. Neuroprotective effect of trans-resveratrol in mild to moderate Alzheimer disease: A randomized, double-blind trial. Neurol. Ther., 2021, 10(2), 905-917.
[http://dx.doi.org/10.1007/s40120-021-00271-2] [PMID: 34402024]
[101]
Song, L.; Chen, L.; Zhang, X.; Li, J.; Le, W. Resveratrol ameliorates motor neuron degeneration and improves survival in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. BioMed Res. Int., 2014, 2014, 1-10.
[http://dx.doi.org/10.1155/2014/483501] [PMID: 25057490]
[102]
Zhu, C.W.; Grossman, H.; Neugroschl, J.; Parker, S.; Burden, A.; Luo, X.; Sano, M. A randomized, double‐blind, placebo‐controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer’s disease: A pilot study. Alzheimers Dement., 2018, 4(1), 609-616.
[http://dx.doi.org/10.1016/j.trci.2018.09.009] [PMID: 30480082]
[103]
Tosatti, J.A.G.; Fontes, A.F.S.; Caramelli, P.; Gomes, K.B. Effects of resveratrol supplementation on the cognitive function of patients with Alzheimer’s disease: A systematic review of randomized controlled trials. Drugs Aging, 2022, 39(4), 285-295.
[http://dx.doi.org/10.1007/s40266-022-00923-4] [PMID: 35187615]
[104]
Broderick, T.L.; Rasool, S.; Li, R.; Zhang, Y.; Anderson, M.; Al-Nakkash, L.; Plochocki, J.H.; Geetha, T.; Babu, J.R. Neuroprotective effects of chronic resveratrol treatment and exercise training in the 3xTg-AD mouse model of Alzheimer’s disease. Int. J. Mol. Sci., 2020, 21(19), 7337.
[http://dx.doi.org/10.3390/ijms21197337] [PMID: 33020412]
[105]
Lin, Y.T.; Wu, Y.C.; Sun, G.C.; Ho, C.Y.; Wong, T.Y.; Lin, C.H.; Chen, H.H.; Yeh, T.C.; Li, C.J.; Tseng, C.J.; Cheng, P.W. Effect of resveratrol on reactive oxygen species-induced cognitive impairment in rats with angiotensin II-induced early alzheimer’s disease †. J. Clin. Med., 2018, 7(10), 329.
[http://dx.doi.org/10.3390/jcm7100329] [PMID: 30301188]
[106]
Yazir, Y.; Utkan, T.; Gacar, N.; Aricioglu, F. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress. Physiol. Behav., 2015, 138, 297-304.
[http://dx.doi.org/10.1016/j.physbeh.2014.10.010] [PMID: 25455865]
[107]
Sarroca, S.; Gatius, A.; Farré, R.E.; Vilchez, D.; Pallàs, M.; Ferré, G.C.; Sanfeliu, C.; Corpas, R. Resveratrol confers neuroprotection against high-fat diet in a mouse model of Alzheimer’s disease via modulation of proteolytic mechanisms. J. Nutr. Biochem., 2021, 89, 108569.
[http://dx.doi.org/10.1016/j.jnutbio.2020.108569] [PMID: 33321185]
[108]
Rachna, G.; Lalit, K.G.; Pramod, K.M.; Swapan, K.B. Effect of resveratrol on scopolamine-induced cognitive impairment in mice. Pharmacol. Rep., 2012, 64(2), 438-444.
[http://dx.doi.org/10.1016/S1734-1140(12)70785-5] [PMID: 22661196]
[109]
Wang, G.; Chen, L.; Pan, X.; Chen, J.; Wang, L.; Wang, W.; Cheng, R.; Wu, F.; Feng, X.; Yu, Y.; Zhang, H.T.; O’Donnell, J.M.; Xu, Y. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling. Oncotarget, 2016, 7(14), 17380-17392.
[http://dx.doi.org/10.18632/oncotarget.8041] [PMID: 26980711]
[110]
Zhang, J.; Feng, X.; Wu, J.; Xu, H.; Li, G.; Zhu, D.; Yue, Q.; Liu, H.; Zhang, Y.; Sun, D.; Wang, H.; Sun, J. Neuroprotective effects of resveratrol on damages of mouse cortical neurons induced by β‐amyloid through activation of SIRT1/Akt1 pathway. Biofactors, 2014, 40(2), 258-267.
[http://dx.doi.org/10.1002/biof.1149] [PMID: 24132831]
[111]
Tabrizian, K.; Shahraki, J.; Bazzi, M.; Rezaee, R.; Jahantigh, H.; Hashemzaei, M. Neuro‐protective effects of resveratrol on carbon monoxide‐induced toxicity in male rats. Phytother. Res., 2017, 31(9), 1310-1315.
[http://dx.doi.org/10.1002/ptr.5855] [PMID: 28635041]
[112]
Zaky, A.; Bassiouny, A.; Farghaly, M.; El-Sabaa, B.M. A combination of resveratrol and curcumin is effective against aluminum chloride-induced neuroinflammation in rats. J. Alzheimers Dis., 2017, 60(s1), S221-S235.
[http://dx.doi.org/10.3233/JAD-161115] [PMID: 28222524]
[113]
Bastianetto, S.; Ménard, C.; Quirion, R. Neuroprotective action of resveratrol. Biochim. Biophys. Acta Mol. Basis Dis., 2015, 1852(6), 1195-1201.
[http://dx.doi.org/10.1016/j.bbadis.2014.09.011] [PMID: 25281824]
[114]
Santos, Q.A.; Gottfried, C. Resveratrol modulates astroglial functions: Neuroprotective hypothesis. Ann. N. Y. Acad. Sci., 2011, 1215(1), 72-78.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05857.x] [PMID: 21261643]
[115]
Kizmazoglu, C.; Aydin, H.E.; Sevin, I.E.; Kalemci, O.; Yüceer, N.; Atasoy, M.A. Neuroprotective effect of resveratrol on acute brain ischemia reperfusion injury by measuring annexin V, p53, Bcl-2 levels in rats. J. Korean Neurosurg. Soc., 2015, 58(6), 508-512.
[http://dx.doi.org/10.3340/jkns.2015.58.6.508] [PMID: 26819684]
[116]
Han, Y.S.; Zheng, W.H.; Bastianetto, S.; Chabot, J.G.; Quirion, R. Neuroprotective effects of resveratrol against β ‐amyloid‐induced neurotoxicity in rat hippocampal neurons: Involvement of protein kinase C. Br. J. Pharmacol., 2004, 141(6), 997-1005.
[http://dx.doi.org/10.1038/sj.bjp.0705688] [PMID: 15028639]
[117]
Karalis, F.; Soubasi, V.; Georgiou, T.; Nakas, C.T.; Simeonidou, C.; Tziampiri, G.O.; Spandou, E. Resveratrol ameliorates hypoxia/ischemia-induced behavioral deficits and brain injury in the neonatal rat brain. Brain Res., 2011, 1425, 98-110.
[http://dx.doi.org/10.1016/j.brainres.2011.09.044] [PMID: 22018692]
[118]
Lin, C.H.; Nicol, C.J.B.; Cheng, Y.C.; Yen, C.; Wang, Y.S.; Chiang, M.C. Neuroprotective effects of resveratrol against oxygen glucose deprivation induced mitochondrial dysfunction by activation of AMPK in SH-SY5Y cells with 3D gelatin scaffold. Brain Res., 2020, 1726, 146492.
[http://dx.doi.org/10.1016/j.brainres.2019.146492] [PMID: 31586626]
[119]
Li, H.; Wang, J.; Wang, P.; Rao, Y.; Chen, L. Resveratrol reverses the synaptic plasticity deficits in a chronic cerebral hypoperfusion rat model. J. Stroke Cerebrovasc. Dis., 2016, 25(1), 122-128.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.09.004] [PMID: 26456198]
[120]
Gocmez, S.S.; Gacar, N.; Utkan, T.; Gacar, G.; Scarpace, P.J.; Tumer, N. Protective effects of resveratrol on aging-induced cognitive impairment in rats. Neurobiol. Learn. Mem., 2016, 131, 131-136.
[http://dx.doi.org/10.1016/j.nlm.2016.03.022] [PMID: 27040098]
[121]
He, X.; Li, Z.; Rizak, J.D.; Wu, S.; Wang, Z.; He, R.; Su, M.; Qin, D.; Wang, J.; Hu, X. Resveratrol attenuates formaldehyde induced hyperphosphorylation of tau protein and cytotoxicity in N2a cells. Front. Neurosci., 2017, 10, 598.
[http://dx.doi.org/10.3389/fnins.2016.00598] [PMID: 28197064]
[122]
Kim, D.W.; Kim, Y.M.; Kang, S.D.; Han, Y.M.; Pae, H.O. Effects of resveratrol and trans-3, 5, 4′-trimethoxystilbene on glutamate-induced cytotoxicity, heme oxygenase-1, and sirtuin 1 in HT22 neuronal cells. Biomol. Ther., 2012, 20(3), 306-312.
[http://dx.doi.org/10.4062/biomolther.2012.20.3.306] [PMID: 24130928]
[123]
Frozza, R.L.; Bernardi, A.; Hoppe, J.B.; Meneghetti, A.B.; Matté, A.; Battastini, A.M.O.; Pohlmann, A.R.; Guterres, S.S.; Salbego, C. Neuroprotective effects of resveratrol against Aβ administration in rats are improved by lipid-core nanocapsules. Mol. Neurobiol., 2013, 47(3), 1066-1080.
[http://dx.doi.org/10.1007/s12035-013-8401-2] [PMID: 23315270]
[124]
Savaskan, E.; Olivieri, G.; Meier, F.; Seifritz, E.; Justice, W.A.; Spahn, M.F. Red wine ingredient resveratrol protects from β-amyloid neurotoxicity. Gerontology, 2003, 49(6), 380-383.
[http://dx.doi.org/10.1159/000073766] [PMID: 14624067]
[125]
Feng, Y.; Wang, X.; Yang, S.; Wang, Y.; Zhang, X.; Du, X.; Sun, X.; Zhao, M.; Huang, L.; Liu, R. Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation. Neurotoxicology, 2009, 30(6), 986-995.
[http://dx.doi.org/10.1016/j.neuro.2009.08.013] [PMID: 19744518]
[126]
Yu, K.C.; Kwan, P.; Cheung, S.K.K.; Ho, A.; Baum, L. Effects of resveratrol and morin on insoluble tau in tau transgenic mice. Transl. Neurosci., 2018, 9(1), 54-60.
[http://dx.doi.org/10.1515/tnsci-2018-0010] [PMID: 30479844]
[127]
Santos, L.M.; Rodrigues, D.; Alemi, M.; Silva, S.C.; Ribeiro, C.A.; Cardoso, I. Resveratrol administration increases Transthyretin protein levels ameliorating AD features- importance of transthyretin tetrameric stability. Mol. Med., 2016, 22(1), 597-607.
[http://dx.doi.org/10.2119/molmed.2016.00124] [PMID: 27385446]

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