Is resveratrol a prospective therapeutic strategy in the co-association of glucose metabolism disorders and neurodegenerative diseases?

References

• Duthey B. Alzheimer disease and other dementias. Alzheimer disease and other dementias a public health approach to innovation. 2013: 1–14.
   Google Scholar
• Sanabria-Castro A, Alvarado Echeverría I, Monge-Bonilla C. Molecular pathogenesis of Alzheimer’s disease : an update. Ann Neurosci. 2017;24:46–54.
   PubMed Web of Science ®Google Scholar
• Gómez-Isla T, Hollister R, Wes H, Growdon JH, Petersen RC, Hyman BT. Neuronal loss correlates with neurofibrillary tangles in Alzheimer. Ann Neurol. 1997;41(1):17–24.
   PubMed Web of Science ®Google Scholar
• Standaert DG, Lee VM, Greenberg BD, Lowery DE, Trojanowskit JQ. Molecular features of hypothalamic plaques in Alzheimer ‘s disease. Am J Pathol. 1991;139(3):681–91.
   PubMed Web of Science ®Google Scholar
• German D, White C, Sparkman D. Alzheimer’s disease: neurofibrillary tangles in nuclei that project to the cerebral cortex. Neuroscience. 1987;21(2):305–12.
   PubMed Web of Science ®Google Scholar
• Braak H, Braak E, Bohl J. Staging of Alzheimer-related cortical destruction. Eur Neurol. 1993;33(6):403–8.
   PubMed Web of Science ®Google Scholar
• Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002;10(1):24–35. http://doi.org/10.1097/00019442-200201000-00004.
   PubMed Web of Science ®Google Scholar
• Mattson M, Barger S, Cheng B, Liederburg I, Smith-Swintosky V, Rydel R. Beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer’s disease. TINS. 1993;16(10):260–3.
   Web of Science ®Google Scholar
• Markesbery WR. Oxidative stress hypothesis in Alzheimer’s disease. Free Radical Biol Med. 1997;23(1):134–47.
   PubMed Web of Science ®Google Scholar
• Su JH, Deng G, Cotman CW. Transneuronal degeneration in the spread of Alzheimer’s disease pathology: immunohistochemical evidence for the transmission of Tau hyperphosphorylation. Neurobiol Dis. 1997;4:365–75.
   PubMed Web of Science ®Google Scholar
• Stadelmann C, Deckwerth TL, Srinivasan A, Bancher C, Jellinger K, Lassmann H. Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer’s disease. Evidence for apoptotic cell death. Am J Pathol. 1999;155(5):1459–66.
   PubMed Web of Science ®Google Scholar
• De FF, Wu D, Lambert MP, Fernandez SJ, Velasco PT, Lacor PN, et al. Alzheimer’s disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers. Neurobiol Aging. 2008;29:1334–47.
   PubMed Web of Science ®Google Scholar
• Forlenza O V, Diniz BS, Gattaz WF. Diagnosis and biomarkers of predementia in Alzheimer’s disease. BMC Med. 2010;8(89):1–14.
   PubMedGoogle Scholar
• Michaud T, Dejun S, Siahpush M, Murman D. The risk of incident mild cognitive impairment and progression to dementia considering mild cognitive impairment subtypes. Dementia Cogn Dis. 2017;7:15–29.
   Web of Science ®Google Scholar
• Ward A, Tardiff S, Dye C, Arrighi HM. Rate of conversion from prodromal Alzheimer’s disease to Alzheimer’s dementia: a systematic review of the literature. Dement Geriatr Cogn Disord. 2013;3:320–32.
   Google Scholar
• Kornhuber J, Wiltfang J, Vos SJB, Verhey F, Fro L, Nobili F, et al. Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage. Brain. 2015;138:1327–38.
   PubMed Web of Science ®Google Scholar
• Huey ED, Manly JJ, Tang M, Brickman AM, Manoochehri M, Mez J, et al. Course and etiology of dysexecutive MCI in a community sample. Alzhemer’s & Dementia. 2013;9(6):632–9.
   PubMed Web of Science ®Google Scholar
• Janson J, Laedtke T, Parisi JE, Brien PO, Petersen RC, Butler PC. Increased risk of type 2 diabetes in Alzheimer disease. Diabetes. 2004;53:474–81.
   PubMed Web of Science ®Google Scholar
• De P-fE, Goldacre R, Pakpoor J, Bch BM, Noyce AJ. Association between diabetes and subsequent Parkinson disease. Neurology. 2018;91(2):e139–42.
   PubMed Web of Science ®Google Scholar
• Degen C, Toro P, Schönknecht P, Sattler C, Schröder J. Diabetes mellitus type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer’s disease. Psychiatry Res. 2016;240:42–6. http://doi.org/10.1016/j.psychres.2016.04.009.
   PubMed Web of Science ®Google Scholar
• DeFronzo R. The triumvirate: p-cell, muscle, liver A collusion responsible for NIDDM. Diabetes. 1988;37:667–87.
   PubMed Web of Science ®Google Scholar
• Butler A, Janson J, Bonner-Weir S, Ritzel R, Rizza R, Butler P. β-Cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003;52:102–10.
   PubMed Web of Science ®Google Scholar
• Ramos-rodriguez JJ, Ortiz O, Jimenez-palomares M, Kay KR, Berrocoso E, Murillo-carretero MI, et al. Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice. Psychoneuroendocrinology. 2013;38(11):2462–75.
   PubMed Web of Science ®Google Scholar
• Liu Z, Patil IY, Jiang T, Sancheti H, Walsh JP. High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity. PLoS One. 2015;10(5):1–16.
   Web of Science ®Google Scholar
• Gao Y, Xiao Y, Miao R, Zhao J, Cui M, Huang G, et al. The prevalence of mild cognitive impairment with type 2 diabetes mellitus among elderly people in China: a cross-sectional study. Arch Gerontol Geriatr. 2016;62:138–42.
   PubMed Web of Science ®Google Scholar
• Biessels GJ, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol. 2018;14(10):591–604.
   PubMed Web of Science ®Google Scholar
• Malik G, Robertson N. Treatments in Alzheimer’s disease. J Neurol. 2017;264(2):416–8.
   PubMed Web of Science ®Google Scholar
• Li J, Deng J, Sheng W, Zuo Z. Metformin attenuates Alzheimer’s disease-like neuropathology in obese, leptin-resistant mice. Pharmacol Biochem Behav. 2012;101(4):564–74.
   PubMed Web of Science ®Google Scholar
• Ou Z, Kong X, Sun X, He X, Zhang L, Gong Z, et al. Metformin treatment prevents amyloid plaque deposition and memory impairment in APP/PS1 mice. Brain Behav Immun. 2017;69:351–63.
   PubMed Web of Science ®Google Scholar
• Ditacchio KA, Heinemann SF, Dziewczapolski G. Metformin treatment alters memory function in a mouse model of Alzheimer’s disease. Journal of Alzheimer’s Disease. 2015;44:43–8.
   PubMed Web of Science ®Google Scholar
• Rocha-Ginzález HI, Ambriz-Tututi M, Granados-soto V. Resveratrol: a natural compound with pharmacological potential in neurodegenerative diseases. CNS Neurosci Ther. 2008;14:234–47.
   PubMed Web of Science ®Google Scholar
• Albani D, Polito L, Signorini A, Forloni G. Neuroprotective properties of resveratrol in different neurodegenerative disorders. Biofactors. 2010;36(5):370–6.
   PubMed Web of Science ®Google Scholar
• Sun AY, Wang Q, Simony A, Sun GY. Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol Neurobiol. 2011;41(2–3):375–83.
   Web of Science ®Google Scholar
• Mecocci P, Tinarelli C, Schulz RJ, Polidori MC. Nutraceuticals in cognitive impairment and Alzheimer’s disease. Front Pharmacol. 2014;5:1–11.
   PubMed Web of Science ®Google Scholar
• Krikorian R, Nash TA, Shidler MD, Shukitt-hale B, Joseph JA. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103:730–4.
   PubMed Web of Science ®Google Scholar
• Brasnyó P, Molnár G, Mohás M, Markó L, Laczy B, Cseh J, et al. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011;106:383–9.
   PubMed Web of Science ®Google Scholar
• Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflam. 2017;14(1):1–10.
   PubMedGoogle Scholar
• Kim YA, Kim G-Y, Park K-Y, Chi YH. Resveratrol inhibits nitric oxide and prostaglandin E2 production by lipopolysaccharide-activated C6 microglia. J Med Food. 2007;10(2):218–24.
   PubMed Web of Science ®Google Scholar
• Spanier G, Xu H, Xia N, Deng S, Wojnowski L, Forstermann U, et al. Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol. 2009;60(Suppl 4):111–6.
   PubMed Web of Science ®Google Scholar
• Féry F. Role of hepatic glucose production and glucose uptake in the pathogenesis of fasting hyperglycemia in type 2 diabetes: normalization of glucose kinetics by short-term fasting. J Clin Endocrinol Metab. 1994;78(3):536–42.
   PubMed Web of Science ®Google Scholar
• Weyer C, Bogardus C, Mott D, Pratley R. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999;104(6):787–94.
   PubMed Web of Science ®Google Scholar
• Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, De La Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reductions in acetylcholine. J Alzheimer’s Dis. 2005;8(3):247–68.
   PubMed Web of Science ®Google Scholar
• de la Monte S, Wands J. Alzheimer’s disease Is type 3 diabetes—evidence reviewed. J Diabetes Sci Technol. 2008;6(2):1101–13.
   Google Scholar
• Withers DJ, White M. The insulin signaling system – a common link in the pathogenesis of type 2 diabetes. Endocrinology. 2000;141(6):1917–21.
   PubMed Web of Science ®Google Scholar
• Geijselaers SLC, Sep SJS, Stehouwer CDA, Biessels GJ. Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review. The Lancet: Diabetes & Endocrinol. 2015;3(1):75–89.
   PubMed Web of Science ®Google Scholar
• Rawlings AM, Sharrett AR, Mosley TH, Ballew SH, Deal JA, Selvin E. Glucose peaks and the risk of dementia and 20-year cognitive decline. Diabetes Care. 2017;40(7):879–86.
   PubMed Web of Science ®Google Scholar
• Greenwood CE, Kaplan RJ, Hebblethwaite S, Jenkins DJA. Carbohydrate-induced memory impairment in adults with type 2 diabetes. Diabetes Care. 2003;26(7):1961–6.
   PubMed Web of Science ®Google Scholar
• Ke YD, Delerue F, Gladbach A, Götz J, Ittner LM. Experimental diabetes mellitus exacerbates Tau pathology in a transgenic mouse model of Alzheimer’s disease. PLoS One. 2009;4(11):1–7.
   Web of Science ®Google Scholar
• Macauley SL, Sutphen CL, David M, Invest JC, Macauley SL, Stanley M, et al. Hyperglycemia modulates extracellular amyloid- β concentrations and neuronal activity in vivo. J Clin Invest. 2015;125(6):2463–7.
   PubMed Web of Science ®Google Scholar
• Lee CC, Huang CC, Sen HK. Insulin promotes dendritic spine and synapse formation by the PI3 K/Akt/mTOR and Rac1 signaling pathways. Neuropharmacology. 2011;61(4):867–79.
   PubMed Web of Science ®Google Scholar
• Costello DA, Claret M, Al-Qassab H, Plattner F, Irvine EE, Choudhury AI, et al. Brain deletion of insulin receptor substrate 2 disrupts hippocampal synaptic plasticity and metaplasticity. PLoS One. 2012;7(2):30–4.
   Web of Science ®Google Scholar
• Li X, Du L, Cheng X, Jiang X, Zhang Y, Lv B, et al. Glycation exacerbates the neuronal toxicity of B-amyloid. Cell Death Dis. 2013;4(6):1–9.
   Google Scholar
• Cole AR, Astell A, Green C, Sutherland C. Molecular connexions between dementia and diabetes. Neurosci Biobehav Rev. 2007;31(7):1046–63.
   PubMed Web of Science ®Google Scholar
• Shepherd PR, Withers DJ, Siddle K. Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem J. 1998;333(3):471–90.
   PubMedGoogle Scholar
• Patel S, Doble BW, MacAulay K, Sinclair EM, Drucker DJ, Woodgett JR. Tissue-specific role of glycogen synthase kinase 3β in glucose homeostasis and insulin action. Mol Cell Biol. 2008;28(20):6314–28.
   PubMed Web of Science ®Google Scholar
• De La Monte SM, Tong M, Schiano I, Didsbury J. Improved brain insulin/IGF signaling and reduced neuroinflammation with T3D-959 in an experimental model of sporadic Alzheimer’s disease. J Alzheimer’s Dis. 2017;55(2):849–64.
   PubMed Web of Science ®Google Scholar
• Desai GS, Zheng C, Geetha T, Mathews ST, White BD, Huggins KW, et al. The pancreas-brain axis: insight into disrupted mechanisms associating type 2 diabetes and Alzheimer’s disease. J Alzheimer’s Dis. 2014;42(2):347–56.
   PubMed Web of Science ®Google Scholar
• Phiel CJ, Wilson CA, Lee VMY, Klein PS. GSK-3α regulates production of Alzheimer’s disease amyloid-β peptides. Nature. 2003;423(6938):435–9.
   PubMed Web of Science ®Google Scholar
• Valente T, Gella A, Fernàndez-Busquets X, Unzeta M, Durany N. Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer’s disease and diabetes mellitus. Neurobiol Dis. 2010;37(1):67–76.
   PubMed Web of Science ®Google Scholar
• Guo C, Zhang S, Li J, Ding C, Yang Z, Chai R, et al. Chronic hyperglycemia induced via the heterozygous knockout of Pdx1 worsens neuropathological lesion in an Alzheimer mouse model. Sci Rep. 2016;6(1):1–14.
   PubMed Web of Science ®Google Scholar
• Umegaki H, Iimuro S, Shinozaki T, Araki A, Sakurai T, Iijima K, et al. Risk factors associated with cognitive decline in the elderly with type 2 diabetes: pooled logistic analysis of a 6-year observation in the Japanese elderly diabetes intervention trial. Geriat Gerontol Int. 2012;12(suppl.1):110–6.
   PubMedGoogle Scholar
• Mushtaq G, Khan JA, Kumosani TA, Kamal MA. Alzheimer’s disease and type 2 diabetes via chronic inflammatory mechanisms. Saudi J Biol Sci. 2015;22(1):4–13.
   PubMed Web of Science ®Google Scholar
• Gorska-Ciebiada M, Saryusz-Wolska M, Borkowska A, Ciebiada M, Adiponectin LJ. Leptin and IL-1 β in elderly diabetic patients with mild cognitive impairment. Metab Brain Dis. 2016;31:257–66.
   PubMed Web of Science ®Google Scholar
• Tansey MG, Mccoy MK, Frank-cannon TC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol. 2007;208:1–25.
   PubMed Web of Science ®Google Scholar
• Rad SK, Arya A, Karimian H, Madhavan P, Rizwan F, Koshy S, et al. Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer’s disease. Drug Des Devel Ther. 2018;12:3999–4021.
   PubMed Web of Science ®Google Scholar
• Bassani TB, Turnes JM, Moura ELR, Bonato JM, Cóppola-segovia V, Zanata SM, et al. Effects of curcumin on short-term spatial and recognition memory, adult neurogenesis and neuroinflammation in a streptozotocin-induced rat model of dementia of Alzheimer’s type. Behav Brain Res. 2017;335:41–54.
   PubMed Web of Science ®Google Scholar
• Taepavarapruk P, Song C. Reductions of acetylcholine release and nerve growth factor expression are correlated with memory impairment induced by interleukin-1β administrations: effects of omega-3 fatty acid EPA treatment. J Neurochem. 2010;112(4):1054–64.
   PubMed Web of Science ®Google Scholar
• Gorska-Ciebiada M, Saryusz-Wolska M, Borkowska A, Ciebiada M, Loba J, Abete P. Serum levels of inflammatory markers in depressed elderly patients with diabetes and mild cognitive impairment. PLoS One. 2015;10(3):1–17.
   Web of Science ®Google Scholar
• Chaney MO, Stine WB, Kokjohn TA, Kuo Y, Esh C, Rahman A, et al. RAGE and amyloid beta interactions: atomic force microscopy and molecular modeling. Biochim Biophys Acta. 2005;1741:199–205.
   PubMed Web of Science ®Google Scholar
• Hsieh H, Chi P, Lin C, Yang C-C, Yang C-M. Up-regulation of ROS-dependent matrix metalloproteinase-9 from high-glucose-challenged astrocytes contributes to the neuronal apoptosis. Mol Neurobiol. 2014;50:520–33.
   PubMed Web of Science ®Google Scholar
• Hsieh C, Liu C, Lee C, Yu L, Wang J. Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self- degradation. Sci Rep. 2019;9(1):1–16.
   PubMedGoogle Scholar
• Jing Y, Chen K, Yang S, Kuo P, Chen J. Resveratrol ameliorates vasculopathy in STZ-induced diabetic rats: role of AGE – RAGE signalling. Diabetes Metab Res Rev. 2010;26(2):212–22.
   PubMedGoogle Scholar
• Zhao H, Li N, Wang Q, Cheng X, Li X, Liu T. Resveratrol decreases the insoluble Aβ1–42 level in hippocampus and protects the integrity of the blood–brain barrier in AD rats. Neuroscience. 2015;310:641–9.
   PubMed Web of Science ®Google Scholar
• Banks WA. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des. 2005;11:973–84.
   PubMed Web of Science ®Google Scholar
• Deane R, Zlokovic B. Role of the blood-brain barrier in the pathogenesis of alzheimers disease. Curr Alzheimer Res. 2007;4(2):191–7.
   PubMed Web of Science ®Google Scholar
• Matrone C, Djelloul M, Taglialatela G, Perrone L. Inflammatory risk factors and pathologies promoting Alzheimer’s disease progression: Is RAGE the key? Histol Histopathol. 2015;30(2):125–39.
   PubMed Web of Science ®Google Scholar
• Yin F, Sancheti H, Patil I, Cadenas E. Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radical Biol Med. 2016;100:108–22.
   PubMed Web of Science ®Google Scholar
• Ma X, Sun Z, Han X, Li S, Jiang X, Chen S, et al. 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):1–11.
   Google Scholar
• Hui Y, Chengyong T, Cheng L, Haixia H, Yuanda Z, Weihua Y. Resveratrol attenuates the cytotoxicity induced by amyloid-β1–42 in PC12 cells by upregulating heme oxygenase-1 via the PI3 K / Akt / Nrf2 pathway. Neurochem Res. 2018;43(2):297–305.
   PubMed Web of Science ®Google Scholar
• Patel MI, Gupta A, Dey CS. Potentiation of neuronal insulin signaling and glucose uptake by resveratrol: the involvement of AMPK. Pharmacol Rep. 2011;63(5):1162–8.
   PubMed Web of Science ®Google Scholar
• Liu M, Yuan C, He J, Tan T, Wu S, Fu H, et al. Resveratrol protects PC12 cells from high glucose-induced neurotoxicity Via PI3 K/Akt/FoxO3a pathway. Cell Mol Neurobiol. 2015;35:513–22.
   PubMed Web of Science ®Google Scholar
• Pallàs M, Casadesús G, Smith MA, Coto-montes A, Pelegri C, Vilaplana J, et al. Resveratrol and neurodegenerative diseases : activation of SIRT1 as the potential pathway towards neuroprotection. Curr Neurovasc Res. 2009;6:70–81.
   PubMed Web of Science ®Google Scholar
• Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in neurons. PNAS. 2007;104(17):7217–22.
   PubMed Web of Science ®Google Scholar
• Carafa V, Rotili D, Forgione M, Cuomo F, Serretiello E, Hailu GS, et al. Sirtuin functions and modulation: from chemistry to the clinic. Clin Epigenetics. 2016;8(61):1–21.
   PubMedGoogle Scholar
• Vassilopoulos A, Fritz KS, Petersen DR, Gius D. The human sirtuin family: evolutionary divergences and functions. Hum Genomics. 2011;5(5):485–96.
   PubMedGoogle Scholar
• Albani D, Polito L, Batelli S, De Mauro S, Fracasso C, Martelli G, et al. The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by alpha-synuclein or amyloid-beta (1-42) peptide. J Neurochem. 2009;110:1445–56.
   PubMed Web of Science ®Google Scholar
• Pan Y, Zhang H, Yuan J, Yu Y, Wang J, Pan Y, et al. Resveratrol exerts entioxidant effects by activating Sirt2 to deacetylate Prx1. Biochemistry. 2017;56(48):6325–8.
   PubMed Web of Science ®Google Scholar
• Bagul PK, Katare PB, Bugga P, Dinda AK, Banerjee S. SIRT-3 modulation by resveratrol improves mitochondrial oxidative phosphorylation in diabetic heart through deacetylation of TFMA. Cells. 2018;7(235):1–13.
   Google Scholar
• Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catorite H, et al. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet. 2005;37(4):349–51.
   PubMed Web of Science ®Google Scholar
• Braidy N, Guillemin G, Grant R. Resveratrol increases intracellular NAD+ levels through up regulation of the adenylyltransferase. Nature Precedings. 2014;1(1):2010.
   Google Scholar
• Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010;285(11):8340–51.
   PubMed Web of Science ®Google Scholar
• Um J, Park S, Kang H, Yang S, Foretz M, Mcburney MW, et al. AMP-activated protein kinase – deficient mice are resistant to the metabolic effects of resveratrol. Diabetes. 2010;59(3):554–63.
   PubMed Web of Science ®Google Scholar
• Hardie DG, Carling D. The AMP-activated protein kinase fuel gauge of the mammalian cell? Eur J Biochem. 1997;246(2):259–73.
   PubMedGoogle Scholar
• Liang J, Shao SH, Xu Z, Hennessy B, Ding Z, Larrea M, et al. The energy sensing LKB1 – AMPK pathway regulates p27 kip1 phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol. 2007;9(2):218–24.
   PubMed Web of Science ®Google Scholar
• Vingtdeux V, Giliberto L, Zhao H, Chandakkar P, Wu Q, Simon JE, et al. AMP-activated protein kinase signaling activation by resveratrol modulates amyloid- β peptide metabolism. J Biol Chem. 2010;285(12):9100–13.
   PubMed Web of Science ®Google Scholar
• Wu Y, Li X, Zhu J, Xie W, Le W, Fan Z, et al. Resveratrol- activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease. NeuroSignals. 2011;19(3):163–74.
   PubMedGoogle Scholar
• Li Z, Han X. Resveratrol alleviates early brain injury following subarachnoid hemorrhage : possible involvement of AMPK/ SIRT1/autophagy signaling pathway. Biol Chem. 2011;399(11):1339–50.
   Google Scholar
• Gu X, Cai Z, Cai M, Liu K, Liu D, Zhang Q, et al. AMPK/SIRT1/p38 MAPK signaling pathway regulates alcohol − induced neurodegeneration by resveratrol. Mol Med Rep. 2018;17:5402–8.
   PubMed Web of Science ®Google Scholar
• Price NL, Gomes AP, Ling AJY, Duarte F V, Martin-montalvo A, North BJ, et al. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 2012;15(5):675–90.
   PubMed Web of Science ®Google Scholar
• Lan F, Weikel KA, Cacicedo JM, Ido Y. Resveratrol-induced AMP-activated protein kinase activation is cell-type dependent: lessons from basic research for clinical application. Nutrients. 2017;9(7):751.
   PubMed Web of Science ®Google Scholar
• Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three akts. Genes Dev. 1999;13(22):2905–27.
   PubMed Web of Science ®Google Scholar
• Sekulić A, Hudson CC, Homme JL, Yin P, Otterness DM, Karnitz LM, et al. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res. 2000;60(13):3504–13.
   PubMed Web of Science ®Google Scholar
• Heras-sandoval D, Pérez-rojas JM, Hernández-damián J, Pedraza-chaverri J. The role of PI3 K / AKT / mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 2014;26:2694–701.
   PubMed Web of Science ®Google Scholar
• Shati AA, Alfaifi MY. Trans -resveratrol inhibits tau phosphorylation in the brains of control and cadmium chloride-treated rats by activating PP2A and PI3 K/Akt induced-inhibition of GSK3β. Neurochem Res. 2019;44(2):357–73.
   PubMed Web of Science ®Google Scholar
• Hou Y, Wang K, Wan W, Cheng Y, Pu X, Ye X. Resveratrol provides neuroprotection by regulating the JAK2/STAT3/PI3 K/AKT/mTOR pathway after stroke in rats. Genes Dis. 2018;5(3):245–55.
   PubMed Web of Science ®Google Scholar
• Lofrumento DD, Saponaro C, Cianciulli A, DeNuccio F, Mitolo V, Nicolardi G, et al. MPTP-Induced Neuroinflammation increases the expression of Pro-inflammatory cytokines and their receptors in mouse brain. Neuroimmunomodulation. 2011;18:79–88.
   PubMed Web of Science ®Google Scholar
• Lofrumento DD, Nicolardi G, Cianciulli A, De NF, La PV, Carofiglio V, et al. Neuroprotective effects of resveratrol in an MPTP mouse model of Parkinson’s-like disease: possible role of SOCS-1 in reducing pro-inflammatory responses. Innate Immun. 2011;18(2):1–12.
   Google Scholar
• Capiralla H, Vingtdeux V, Zhao H, Sankowski R, Al-Abed Y, Marambaud P, et al. Resveratrol mitigates lipopolysaccharide- and Aβ-mediated microglial inflammation by inhibiting the TLR4/NF-κB/STAT signaling cascade. J Neurochem. 2013;120(3):461–72.
   Web of Science ®Google Scholar
• Imler TJ, Petro TM. Decreased severity of experimental autoimmune encephalomyelitis during resveratrol administration is associated with increased IL-17 + IL-10 + T cells, CD4− IFN- γ + cells, and decreased macrophage IL-6 expression. Int Immunopharmacol. 2009;9(1):134–43.
   PubMed Web of Science ®Google Scholar
• Das S, Das DK. Anti-Inflammatory responses of resveratrol. Inflamm Allergy-Drug Targets. 2007;6:168–73.
   PubMedGoogle Scholar
• Wiedemann J, Rashid K, Langmann T. Biochemical and Biophysical Research Communications resveratrol induces dynamic changes to the microglia transcriptome, inhibiting inflammatory pathways and protecting against microglia- mediated photoreceptor apoptosis. Biochem Biophys Res Commun. 2018;501(1):239–45.
   PubMed Web of Science ®Google Scholar
• Jin F, Wu Q, Lu Y, Gong Q, Shi J. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur J Pharmacol. 2008;600(1–3):78–82.
   PubMed Web of Science ®Google Scholar
• Zhao H, Wang Q, Cheng X, Li X, Li N, Liu T, et al. Inhibitive effect of resveratrol on the inflammation in cultured astrocytes and microglia induced by Aβ1-42. Neuroscience. 2018;379:390–404.
   PubMed Web of Science ®Google Scholar
• Coutinho DDS, Pacheco MT, Frozza RL, Bernardi A. Anti-Inflammatory effects of resveratrol: mechanistic insights. Int J Mol Sci. 2018;19(1812):1–25.
   Google Scholar
• Shi L, Zhang Z, Li L, Hölscher C. A novel dual GLP-1/GIP receptor agonist alleviates cognitive decline by re-sensitizing insulin signaling in the Alzheimer icv. STZ rat model. Behav Brain Res. 2017;327:65–74.
   PubMed Web of Science ®Google Scholar
• Yu Y, Li X, Blanchard J, Li Y, Iqbal K, Liu F, et al. Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice. J Neural Transm. 2015;122(4):593–606.
   PubMed Web of Science ®Google Scholar
• Adzovic L, Lynn AE, Angelo HMD, Crockett AM, Kaercher RM, Royer SE, et al. Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains. J Neuroinflammation. 2015;12(63):1–10.
   Google Scholar
• Gejl M, Gjedde A, Egefjord L, Møller A, Hansen SB, Vang K, et al. In Alzheimer’s disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism : randomized, clinical trial. Front Aging Neurosci. 2016;8:1–10.
   PubMed Web of Science ®Google Scholar
• Weinstein G, Davis-plourde KL, Conner S, Himali JJ, Beiser AS, Lee A, et al. Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer’s disease: Pooled analysis from 5 cohorts. PLoS One. 2019;14(2):1–18.
   Web of Science ®Google Scholar
• Khazaei M, Karimi J, Sheikh N, Goodarzi MT. Effects of resveratrol on receptor for advanced glycation End products (RAGE) expression and oxidative stress in the liver of rats with type 2 diabetes. Phytother Res. 2016;30:66–71.
   PubMed Web of Science ®Google Scholar
• Tian Z, Wang J, Xu M, Wang Y, Zhang M, Zhou Y. Resveratrol improves cognitive impairment by regulating apoptosis and synaptic plasticity in streptozotocin-induced diabetic rats. Cell Physiol Biochem. 2016;40(6):1670–7.
   PubMedGoogle Scholar
• Jing Y, Chen K, Kuo P, Pao C, Chen J-K. Neurodegeneration in streptozotocin- induced diabetic rats is attenuated by treatment with resveratrol. Neuroendocrinology. 2013;98(2):116–27.
   PubMed Web of Science ®Google Scholar
• Tian X, Liu Y, Ren G, Yin L, Liang X, Geng T, et al. Resveratrol limits diabetes-associated cognitive decline in rats by preventing oxidative stress and inflammation and modulating hippocampal structural synaptic plasticity. Brain Res. 2016;1650:1–9.
   PubMed Web of Science ®Google Scholar
• Bernier M, Wahl D, Ali A, Allard J, Faulkner S, Sanghvi M, et al. Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high - fat/sucrose diet. Aging. 2016;8(5):899–914.
   PubMedGoogle Scholar
• Kodali M, Parihar VK, Hattiangady B, Mishra V, Shuai B, Shetty AK. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation. Sci Rep. 2015;5:8075.
   PubMed Web of Science ®Google Scholar
• Porquet D, Casadesús G, Bayod S, Vicente A, Canudas AM, Vilaplana J, et al. Dietary resveratrol prevents Alzheimer’s markers and increases life span in SAMP8. Age (Omaha). 2013;35:1851–65.
   PubMedGoogle Scholar
• Gocmez SS, Gacar N, Utkan T, Gacar G, Scarpace PJ, Tumer N. Protective effects of resveratrol on aging-induced cognitive impairment in rats. Neurobiol Learn Mem. 2016;131:131–6.
   PubMed Web of Science ®Google Scholar
• Rege SD, Geetha T, Broderick TL, Babu JR. Resveratrol Protects β amyloid-induced oxidative damage and memory associated proteins in H19-7 hippocampal neuronal cells. Curr Alzheimer Res. 2015;12:147–56.
   PubMed Web of Science ®Google Scholar
• Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012;32(7):537–41.
   PubMed Web of Science ®Google Scholar
• Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, Hawkins M, et al. Pilot study of resveratrol in older adults With impaired glucose tolerance. J Gerontol: Series A. 2012 Dec;67(12):1307–12.
   PubMed Web of Science ®Google Scholar
• Movahed A, Nabipour I, Lieben Louis X, Thandapilly SJ, Yu L, Kalantarhormozi M, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evidence-Based Complemen Altern Med. 2013;2013:1–11.
   Web of Science ®Google Scholar
• Turner RS, Thomas RG, Craft S, Van DC, Mintzer J, Reynolds BA, et al. A randomized double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85(16):1383–91.
   PubMed Web of Science ®Google Scholar
• Köbe T, Witte AV, Schnelle A, Tesky VA, Pantel J, Schuchardt J, et al. Impact of resveratrol on glucose control, hippocampal structure and connectivity, and memory performance in patients with mild cognitive impairment. Front Neurosci. 2017;11:1–11.
   PubMed Web of Science ®Google Scholar
• Wong RHX, Nealon RS, Scholey A, Howe PRC. Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus. nutrition. Metabol Cardiovas Dis. 2016;26:393–9.
   PubMed Web of Science ®Google Scholar
• Soleas GJ, Diamandis EP, Goldberg DM. Wine as a biological fluid: history, production, and role in disease prevention. J Clin Lab Anal. 1997;11:287–313.
   PubMed Web of Science ®Google Scholar
• Subramanian L, Youssef S, Bhattacharya S, Kenealey J, Polans AS, Ginkel Pv. Resveratrol: challenges in translation to the clinic – a critical discussion. Clin Cancer Res. 2010;16(24):5942–8.
   PubMed Web of Science ®Google Scholar
• Visioli F. The resveratrol fiasco. Pharmacol Res. 2014;90:87.
   PubMed Web of Science ®Google Scholar
• Park EJ, Pezzuto JM. The pharmacology of resveratrol in animals and humans. Biochimica et Biophysica Acta - Molecular Basis of Disease. 2015;1852(6):1071–113.
   PubMed Web of Science ®Google Scholar
• Walle T. Bioavailability of resveratrol. Ann N Y Acad Sci. 2011 Jan;1215(1):9–15.
   PubMed Web of Science ®Google Scholar
• Rotches-Ribalta M, Andres-Lacueva C, Estruch R, Escribano E, Urpi-Sarda M. Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets. Pharmacol Res. 2012 Nov;66(5):375–82.
   PubMed Web of Science ®Google Scholar
• Amri A, Chaumeil JC, Sfar S, Charrueau C. Administration of resveratrol: what formulation solutions to bioavailability limitations? J Controlled Release. 2012 Mar;158(2):182–93.
   PubMed Web of Science ®Google Scholar
• Shaito A, Posadino AM, Younes N, Hasan H, Halabi S, Alhababi D, et al. Potential adverse effects of resveratrol: a literature review. Int J Mol Sci. 2020;21(6):1–26.
   Web of Science ®Google Scholar
• Murata M, Takahashi A, Saito I, Kawanishi S. Site-specific DNA methylation and apoptosis: induction by diabetogenic streptozotocin. Biochem Pharmacol. 1999;57(8):881–7.
   PubMed Web of Science ®Google Scholar
• Wang YW, Sun GD, Sun J, Liu SJ, Wang J, Xu XH, et al. Spontaneous type 2 diabetic rodent models. J Diabetes Res. 2013;2013, Article ID 401723. https://doi.org/10.1155/2013/401723.
   Google Scholar
• Skovsø S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. J Diabetes Investig. 2014;5(4):349–58.
   PubMed Web of Science ®Google Scholar
• Harada N, Zhao J, Kurihara H, Nakagata N, Okajima K. Resveratrol improves cognitive function in mice by increasing production of insulin-like growth factor-I in the hippocampus. J Nutr Biochem. 2011;22(12):1150–9.
   PubMed Web of Science ®Google Scholar
• Chi T-C, Chen W-P, Chi T-L, Kuo T-F, Lee S-S, Cheng J-T, et al. Phosphatidylinositol-3-kinase is involved in the antihyperglycemic effect induced by resveratrol in streptozotocin-induced diabetic rats. Life Sci. 2007 Apr;80(18):1713–20.
   PubMed Web of Science ®Google Scholar
• Chang C-C, Chang C-Y, Wu Y-T, Huang J-P, Yen T-H, Hung L-M. Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase. J Biomed Sci. 2011;18(1):47.
   PubMed Web of Science ®Google Scholar
• Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, Corrêa M, et al. Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2009;610(1–3):42–8.
   PubMed Web of Science ®Google Scholar
• Zhao H, Niu Q, Li X, Liu T, Xu Y, Han H, et al. Long-term resveratrol consumption protects ovariectomized rats chronically treated with d-galactose from developing memory decline without effects on the uterus. Brain Res. 2012 Jul;1467:67–80.
   PubMed Web of Science ®Google Scholar
• Wang YJ, Thomas P, Zhong JH, Bi FF, Kosaraju S, Pollard A, et al. Consumption of grape seed extract prevents amyloid-β deposition and attenuates inflammation in brain of an Alzheimer’s disease mouse. Neurotox Res. 2009;15(1):3–14.
   PubMed Web of Science ®Google Scholar
• Sharma M, Gupta Y. Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sci. 2002 Oct;71(21):2489–98.
   PubMed Web of Science ®Google Scholar
• Jeon BT, Jeong EA, Shin HJ, Lee Y, Lee DH, Kim HJ, et al. Resveratrol attenuates obesity-associated peripheral and central inflammation and improves memory deficit in mice Fed a high-Fat diet. Diabetes. 2012 Jun 1;61(6):1444–54.
   PubMed Web of Science ®Google Scholar
• Wang J, Ho L, Zhao Z, Seror I, Humala N, Dickstein DL, et al. Moderate consumption of Cabernet sauvignon attenuates Aβ neuropathology in a mouse model of Alzheimer’s disease. FASEB J. 2006 Nov;20(13):2313–20.
   PubMed Web of Science ®Google Scholar
• Oomen CA, Farkas E, Roman V, van der Beek EM, Luiten PGM, Meerlo P. Resveratrol preserves cerebrovascular density and cognitive function in aging mice. Front Aging Neurosci. 2009;1:1–9.
   PubMed Web of Science ®Google Scholar
• Kumar A, Naidu PS, Seghal N, Padi SSV. Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. Pharmacology. 2007;79(1):17–26.
   PubMed Web of Science ®Google Scholar