Generic placeholder image

Current Nutrition & Food Science

Author(s): Farbod Hatami, Tahereh Farkhondeh, Alia Mohaqeq, Niloufar Valizadeh, Michael Aschner, Effat Alemzadeh* and Saeed Samarghandian*

DOI: 10.2174/0115734013278925240507044009

DownloadDownload PDF Flyer Cite As
Quercetin's Neuroprotective Role: Activating Nrf2 Signaling Pathways

  • * (Excluding Mailing and Handling)

Abstract

With the global elderly population projected to double by 2050, there is an increasing need to address the risk factors associated with neurodegenerative diseases. This article focuses on exploring the potential neuroprotective effects of quercetin mediated through the Nrf2 signaling pathway. Quercetin, a flavonoid pigment known for its antioxidant properties, can directly interact with Keap1, leading to the dissociation of Nrf2 from the Keap1-Nrf2 complex. Consequently, Nrf2 is released and translocates to the nucleus, initiating the transcription of antioxidant enzymes, such as heme oxygenase-1, NAD(P) H: quinone oxidoreductase 1, and glutathione S-transferase. The exploration of quercetin as an Nrf2 activator holds significant therapeutic implications for neurodegenerative disorders. Human studies demonstrate the efficacy of quercetin in neurodegenerative diseases, while animal studies highlight the protective effects of the Nrf2 signaling pathway. Additionally, Nrf2 regulates proinflammatory cytokines. This study aims to investigate the potential neuroprotective effects of quercetin mediated through the Nrf2 signaling pathway. By targeting oxidative stress, neuroinflammation, and improving mitochondrial function, quercetin shows promise as a candidate for preventing or slowing the progression of neurodegenerative diseases.

[1]
Rauf A, Imran M, Khan IA, et al. Anticancer potential of quercetin: A comprehensive review. Phytother Res 2018; 32(11): 2109-30.
[http://dx.doi.org/10.1002/ptr.6155] [PMID: 30039547]
[2]
Boots AW, Haenen GR, Bast A. Health effects of quercetin: From antioxidant to nutraceutical. Eur J Pharmacol 2008; 585(2-3): 325-37.
[PMID: 18417116]
[3]
Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules 2019; 24(6): 1123.
[PMID: 30901869]
[4]
Alemzadeh E, Karamian M, Abedi F, Hanafi-Bojd MY. Topical treatment of cutaneous leishmaniasis lesions using quercetin/ Artemisia-capped silver nanoparticles ointment: Modulation of inflammatory response. Acta Trop 2022; 228: 106325.
[PMID: 35093324]
[5]
Ebrahimzadeh A. Topically applied luteolin/quercetin-capped silver nanoparticle ointment as antileishmanial composite: Acceleration wound healing in BALB/c mice. Adv Mater Sci Eng 2023; 2023: 1-11.
[6]
Kohandel Z, Farkhondeh T, Aschner M, Pourbagher-Shahri AM, Samarghandian S. Anti-inflammatory action of astaxanthin and its use in the treatment of various diseases. Pharmacotherapy 2022; 1(145): 112179.
[7]
Samarghandian S, Hadjzadeh MA, Afshari JT, Hosseini M. Antiproliferative activity and induction of apoptotic by ethanolic extract of Alpinia galanga rhizhome in human breast carcinoma cell line. BMC Comp Alt Med 2014; 14: 1-9.
[PMID: 18284912]
[8]
Ashrafizadeh M, Ahmadi Z, Farkhondeh T, Samarghandian S. Resveratrol targeting the Wnt signaling pathway: A focus on therapeutic activities. J Cell Physiol 2020; 235(5): 4135-4145. Epub 2019 Oct 21.
[http://dx.doi.org/10.1002/jcp.29327] [PMID: 31637721]
[9]
Samarghandian S, Borji A, Tabasi SH. Effects of Cichorium intybus linn on blood glucose, lipid constituents and selected oxidative stress parameters in streptozotocin-induced diabetic rats. Cardiovasc Hematol Disord Drug Targets 2013; 13(3): 231-6.
[http://dx.doi.org/10.2174/1871529x13666131129103139]
[10]
Ashrafizadeh M, Fekri HS, Ahmadi Z, Farkhondeh T, Samarghandian S. Therapeutic and biological activities of berberine: The involvement of Nrf2 signaling pathway. J Cell Biochem 2020; 121(2): 1575-1585.
[http://dx.doi.org/10.1002/jcb.29392] [PMID: 31609017]
[11]
El-Horany HE, El-Latif RN, ElBatsh MM, Emam MN. Ameliorative effect of quercetin on neurochemical and behavioral deficits in rotenone rat model of Parkinson’s disease: Modulating autophagy (quercetin on experimental Parkinson’s disease). J Biochem Mol Toxicol 2016; 30(7): 360-9.
[PMID: 27252111]
[12]
Elumalai P, Lakshmi S. Role of quercetin benefits in neurodegeneration. Adv Neurobiol 2016; 12: 229-45.
[13]
Costa LG. Mechanisms of neuroprotection by quercetin: Counteracting oxidative stress and more. Oxid Med Cell Longev 2016; 2016: 2986796.
[http://dx.doi.org/10.1155/2016/2986796]
[14]
Ashrafizadeh M, Zarrabi A, Orouei S. et al. MicroRNA-mediated autophagy regulation in cancer therapy: the role in chemoresistance/chemosensitivity. Eur J Pharmacol 2021; 5(892): 173660
[15]
Linseman DA. Targeting oxidative stress for neuroprotection. Antioxid Redox Signal 2009; 11(3): 421-4.
[http://dx.doi.org/10.1089/ars.2008.2236] [PMID: 18715147]
[16]
Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci USA 1994; 91(21): 9926-30.
[http://dx.doi.org/10.1073/pnas.91.21.9926] [PMID: 7937919]
[17]
Johnson JA, Johnson DA, Kraft AD, et al. The Nrf2-ARE pathway: An indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 2008; 1147(1): 61-9.
[http://dx.doi.org/10.1196/annals.1427.036] [PMID: 19076431]
[18]
Lee JM, Calkins MJ, Chan K, Kan YW, Johnson JA. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 2003; 278(14): 12029-38.
[http://dx.doi.org/10.1074/jbc.M211558200] [PMID: 12556532]
[19]
Shih AY, Johnson DA, Wong G, et al. Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci 2003; 23(8): 3394-406.
[http://dx.doi.org/10.1523/JNEUROSCI.23-08-03394.2003] [PMID: 12716947]
[20]
Gan L, Johnson JA. Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim Biophys Acta Mol Basis Dis 2014; 1842(8): 1208-18.
[http://dx.doi.org/10.1016/j.bbadis.2013.12.011] [PMID: 24382478]
[21]
Shih AY, Imbeault S, Barakauskas V, et al. Induction of the Nrf2-driven antioxidant response confers neuroprotection during mitochondrial stress in vivo. J Biol Chem 2005; 280(24): 22925-36.
[http://dx.doi.org/10.1074/jbc.M414635200] [PMID: 15840590]
[22]
Liang L, Gao C, Luo M, et al. Dihydroquercetin (DHQ) induced HO-1 and NQO1 expression against oxidative stress through the Nrf2-dependent antioxidant pathway. J Agric Food Chem 2013; 61(11): 2755-61.
[http://dx.doi.org/10.1021/jf304768p] [PMID: 23419114]
[23]
Nouhi F, Tusi SK, Abdi A, Khodagholi F. Dietary supplementation with tBHQ, an Nrf2 stabilizer molecule, confers neuroprotection against apoptosis in amyloid β-injected rat. Neurochem Res 2011; 36(5): 870-8.
[http://dx.doi.org/10.1007/s11064-011-0417-2] [PMID: 21293924]
[24]
Arredondo F, Echeverry C, Abin-Carriquiry JA, et al. After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult. Free Radic Biol Med 2010; 49(5): 738-47.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.05.020] [PMID: 20554019]
[25]
Granado-Serrano AB, Martín MA, Bravo L, Goya L, Ramos S. Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38. Chem Biol Interact 2012; 195(2): 154-64.
[http://dx.doi.org/10.1016/j.cbi.2011.12.005] [PMID: 22197970]
[26]
Saw CLL, Guo Y, Yang AY, et al. The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: Involvement of the Nrf2-ARE signaling pathway. Food Chem Toxicol 2014; 72: 303-11.
[http://dx.doi.org/10.1016/j.fct.2014.07.038] [PMID: 25111660]
[27]
Vickers NJ. Animal communication: When I’m calling you, will you answer too? Curr Biol 2017; 27(14): R713-5.
[PMID: 28743020]
[28]
Sharma VK, Singh TG. Insulin resistance and bioenergetic manifestations: Targets and approaches in Alzheimer’s disease. Life Sci 2020; 262: 118401.
[PMID: 32926928]
[29]
Sharma VK, Mehta V, Singh TG. Alzheimer’s disorder: Epigenetic connection and associated risk factors. Curr Neuropharmacol 2020; 18(8): 740-53.
[http://dx.doi.org/10.2174/1570159X18666200128125641] [PMID: 31989902]
[30]
Sharma VK, Singh TG. Navigating Alzheimer’s disease via chronic stress: The role of glucocorticoids. Curr Drug Targets 2020; 21(5): 433-44.
[PMID: 31625472]
[31]
Kim WS, Kågedal K, Halliday GM. Alpha-synuclein biology in Lewy body diseases. Alzheimers Res Ther 2014; 6(5): 73.
[PMID: 25580161]
[32]
Thapa K, Khan H, Sharma U, Grewal AK, Singh TG. Poly (ADP-ribose) polymerase-1 as a promising drug target for neurodegenerative diseases. Life Sci 2021; 267: 118975.
[http://dx.doi.org/10.1016/j.lfs.2020.118975] [PMID: 33387580]
[33]
Kanaan NM, Manfredsson FP. Loss of functional alpha-synuclein: A toxic event in Parkinson’s disease? J Parkinsons Dis 2012; 2(4): 249-67.
[PMID: 23938255]
[34]
De Vos KJ, Grierson AJ, Ackerley S, Miller CC. Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci 2008; 31: 151-73.
[PMID: 18558852]
[35]
Purves D. Circuits within the basal ganglia system. Neuroscience. (2nd ed.), Sunderland, Massachusetts: Sinauer Associates 2001.
[36]
Crossman AR. Functional anatomy of movement disorders. J Anat 2000; 196(Pt 4): 519-25.
[PMID: 10923984]
[37]
Iriti M, Vitalini S, Fico G, Faoro F. Neuroprotective herbs and foods from different traditional medicines and diets. Molecules 2010; 15(5): 3517-55.
[PMID: 20657497]
[38]
Goldenberg MM. Medical management of Parkinson’s disease. P&T 2008; 33(10): 590-606.
[PMID: 19750042]
[39]
Dinkova-Kostova AT, Kostov RV, Kazantsev AG. The role of Nrf2 signaling in counteracting neurodegenerative diseases. FEBS J 2018; 285(19): 3576-90.
[PMID: 29323772]
[40]
Esteras N, Dinkova-Kostova AT, Abramov AY. Nrf2 activation in the treatment of neurodegenerative diseases: A focus on its role in mitochondrial bioenergetics and function. Biol Chem 2016; 397(5): 383-400.
[PMID: 26812787]
[41]
Kobayashi EH, Suzuki T, Funayama R, et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun 2016; 7(1): 11624.
[PMID: 27211851]
[42]
Liu R, Yang J, Li Y, Xie J, Wang J. Heme oxygenase-1: The roles of both good and evil in neurodegenerative diseases. J Neurochem 2023; 167(3): 347-61.
[PMID: 37746863]
[43]
Paladino S, Conte A, Caggiano R, Pierantoni GM, Faraonio R. Nrf2 pathway in age-related neurological disorders: Insights into MicroRNAs. Cell Physiol Biochem 2018; 47(5): 1951-76.
[PMID: 29969760]
[44]
Lu MC, Ji JA, Jiang ZY, You QD. The Keap1–Nrf2–ARE pathway as a potential preventive and therapeutic target: An update. Med Res Rev 2016; 36(5): 924-63.
[http://dx.doi.org/10.1002/med.21396] [PMID: 27192495]
[45]
Si Z, Wang X. The neuroprotective and neurodegeneration effects of heme oxygenase-1 in Alzheimer’s disease. J Alzheimers Dis 2020; 78(4): 1259-72.
[http://dx.doi.org/10.3233/JAD-200720] [PMID: 33016915]
[46]
Jazwa A, Cuadrado A. Targeting heme oxygenase-1 for neuroprotection and neuroinflammation in neurodegenerative diseases. Curr Drug Targets 2010; 11(12): 1517-31.
[http://dx.doi.org/10.2174/1389450111009011517] [PMID: 20704549]
[47]
Wu YH, Hsieh HL. Roles of heme oxygenase-1 in neuroinflammation and brain disorders. Antioxidants 2022; 11(5): 923.
[http://dx.doi.org/10.3390/antiox11050923] [PMID: 35624787]
[48]
Shen X, Hu B, Xu G, et al. Activation of Nrf2/HO-1 pathway by glycogen synthase kinase-3β inhibition attenuates renal ischemia/reperfusion injury in diabetic rats. Kidney Blood Press Res 2017; 42(2): 369-78.
[http://dx.doi.org/10.1159/000477947] [PMID: 28624830]
[49]
Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 2009; 284(20): 13291-5.
[http://dx.doi.org/10.1074/jbc.R900010200] [PMID: 19182219]
[50]
Tu W, Wang H, Li S, Liu Q, Sha H. The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases. Aging Dis 2019; 10(3): 637-51.
[http://dx.doi.org/10.14336/AD.2018.0513] [PMID: 31165007]
[51]
Moratilla-Rivera I, Sánchez M, Valdés-González JA, Gómez-Serranillos MP. Natural products as modulators of Nrf2 signaling pathway in neuroprotection. Int J Mol Sci 2023; 24(4): 3748.
[http://dx.doi.org/10.3390/ijms24043748] [PMID: 36835155]
[52]
Singh S, Nagalakshmi D, Sharma KK, Ravichandiran V. Natural antioxidants for neuroinflammatory disorders and possible involvement of Nrf2 pathway: A review. Heliyon 2021; 7(2): e06216.
[http://dx.doi.org/10.1016/j.heliyon.2021.e06216] [PMID: 33659743]
[53]
Huang Y, Li W, Su Z, Kong ANT. The complexity of the Nrf2 pathway: Beyond the antioxidant response. J Nutr Biochem 2015; 26(12): 1401-13.
[http://dx.doi.org/10.1016/j.jnutbio.2015.08.001] [PMID: 26419687]
[54]
Zhang N, Shu HY, Huang T, et al. Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity. PLoS One 2014; 9(6): e100286.
[http://dx.doi.org/10.1371/journal.pone.0100286] [PMID: 24959672]
[55]
Mattson MP, Cheng A. Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal stress responses. Trends Neurosci 2006; 29(11): 632-9.
[http://dx.doi.org/10.1016/j.tins.2006.09.001] [PMID: 17000014]
[56]
Soheyli E, Azad D, Sahraei R, Hatamnia AA, Rostamzad A, Alinazari M. Synthesis and optimization of emission characteristics of water-dispersible ag-in-s quantum dots and their bactericidal activity. Colloids Surf B Biointerfaces 2019; 182: 110389.
[http://dx.doi.org/10.1016/j.colsurfb.2019.110389] [PMID: 31377610]
[57]
Moreno LCGI, Puerta E, Suárez-Santiago JE, Santos-Magalhães NS, Ramirez MJ, Irache JM. Effect of the oral administration of nanoencapsulated quercetin on a mouse model of Alzheimer’s disease. Int J Pharm 2017; 517(1-2): 50-7.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.061] [PMID: 27915007]
[58]
Men K. Nanoparticle-delivered quercetin for cancer therapy. Anticancer Agents Med Chem 2014; 14(6): 826-32.
[http://dx.doi.org/10.2174/1871520614666140521122932]
[59]
Qi P, Li J, Gao S, et al. Network pharmacology-based and experimental identification of the effects of quercetin on Alzheimer’s disease. Front Aging Neurosci 2020; 12: 589588.
[http://dx.doi.org/10.3389/fnagi.2020.589588] [PMID: 33192484]
[60]
Liao X, Ge K, Cai Z, et al. Hybridization chain reaction triggered poly adenine to absorb silver nanoparticles for label-free electrochemical detection of Alzheimer’s disease biomarkers amyloid β-peptide oligomers. Anal Chim Acta 2022; 1192: 339391.
[http://dx.doi.org/10.1016/j.aca.2021.339391] [PMID: 35057926]
[61]
Samarghandian S, Azimi-Nezhad M, Borji A, Farkhondeh T. Effect of crocin on aged rat kidney through inhibition of oxidative stress and proinflammatory state. Phytotherapy Res 2016; 30(8): 1345-53.
[62]
Kahroba H, Ramezani B, Maadi H, Sadeghi MR, Jaberie H, Ramezani F. The role of Nrf2 in neural stem/progenitors cells: From maintaining stemness and self-renewal to promoting differentiation capability and facilitating therapeutic application in neurodegenerative disease. Ageing Res Rev 2021; 65: 101211.
[http://dx.doi.org/10.1016/j.arr.2020.101211] [PMID: 33186670]
[63]
Osama A, Zhang J, Yao J, Yao X, Fang J. Nrf2: A dark horse in Alzheimer’s disease treatment. Ageing Res Rev 2020; 64: 101206.
[http://dx.doi.org/10.1016/j.arr.2020.101206] [PMID: 33144124]
[64]
Saha S, Buttari B, Profumo E, Tucci P, Saso L. A perspective on Nrf2 signaling pathway for neuroinflammation: A potential therapeutic target in Alzheimer’s and Parkinson’s diseases. Front Cell Neurosci 2022; 15: 787258.
[http://dx.doi.org/10.3389/fncel.2021.787258] [PMID: 35126058]
[65]
Joshi G, Gan KA, Johnson DA, Johnson JA. Increased Alzheimer’s disease–like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy. Neurobiol Aging 2015; 36(2): 664-79.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.09.004] [PMID: 25316599]
[66]
Bahn G, Park JS, Yun UJ, et al. NRF2/ARE pathway negatively regulates BACE1 expression and ameliorates cognitive deficits in mouse Alzheimer’s models. Proc Natl Acad Sci USA 2019; 116(25): 12516-23.
[http://dx.doi.org/10.1073/pnas.1819541116] [PMID: 31164420]
[67]
Boesch-Saadatmandi C, Wolffram S, Minihane AM, Rimbach G. Effect of apoE genotype and dietary quercetin on blood lipids and TNF-α levels in apoE3 and apoE4 targeted gene replacement mice. Br J Nutr 2009; 101(10): 1440-3.
[http://dx.doi.org/10.1017/S0007114508102434] [PMID: 18986596]
[68]
Zhang X, Hu J, Zhong L, et al. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice. Neuropharmacology 2016; 108: 179-92.
[PMID: 27114256]
[69]
Ebrahimpour S, Shahidi SB, Abbasi M, Tavakoli Z, Esmaeili A. Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) increases Nrf2 expression via miR-27a mediation to prevent memory dysfunction in diabetic rats. Sci Rep 2020; 10(1): 15957.
[http://dx.doi.org/10.1038/s41598-020-71971-2] [PMID: 32994439]
[70]
Ashrafizadeh M, Ahmadi Z, Kotla NG, Afshar EG, Samarghandian S, Mandegary A, Pardakhty A, Mohammadinejad R, Sethi G. Nanoparticles targeting STATs in cancer therapy. Cells 2019; 8(10): 1158.
[71]
Lee M, McGeer EG, McGeer PL. Quercetin, not caffeine, is a major neuroprotective component in coffee. Neurobiol Aging 2016; 46: 113-23.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.06.015] [PMID: 27479153]
[72]
Yu X, Li Y, Mu X. ffect of Quercetin on PC12 Alzheimer's Disease cell model induced by Aβ25-35 and its mechanism based on Sirtuin1/Nrf2/HO-1 pathway. Biomed Res Int 2020; 2020: 8210578.
[73]
Zaplatic E, Bule M, Shah SZA, Uddin MS, Niaz K. Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer’s disease. Life Sci 2019; 224: 109-19.
[PMID: 30914316]
[74]
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology 2009; 72(21) (Suppl. 4): S1-S136.
[PMID: 19470958]
[75]
Panaro MA, Cianciulli A. Current opinions and perspectives on the role of immune system in the pathogenesis of Parkinson’s disease. Curr Pharm Des 2012; 18(2): 200-8.
[PMID: 22229581]
[76]
Ighodaro O, Akinloye O. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex J Med 2018; 54(4): 287-93.
[77]
Jiang Y, Xie G, Alimujiang A, et al. Protective effects of Querectin against MPP+-induced dopaminergic neurons injury via the Nrf2 signaling pathway. Front Biosci-Landmark 2023; 28(3): 42.
[PMID: 37005755]
[78]
Xiong Y, Mahmood A, Chopp M. Animal models of traumatic brain injury. Nat Rev Neurosci 2013; 14(2): 128-42.
[PMID: 23329160]
[79]
Carroll LJ, Cassidy JD, Cancelliere C, et al. Systematic review of the prognosis after mild traumatic brain injury in adults: Cognitive, psychiatric, and mortality outcomes: Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis. Arch Phys Med Rehabil 2014; 95(3): S152-73.
[PMID: 24581903]
[80]
Yang T, Kong B, Gu JW, et al. Anti-apoptotic and anti-oxidative roles of quercetin after traumatic brain injury. Cell Mol Neurobiol 2014; 34(6): 797-804.
[http://dx.doi.org/10.1007/s10571-014-0070-9] [PMID: 24846663]
[81]
Li X, Wang H, Gao Y, et al. Protective effects of quercetin on mitochondrial biogenesis in experimental traumatic brain injury via the Nrf2 signaling pathway. PLoS One 2016; 11(10): e0164237.
[http://dx.doi.org/10.1371/journal.pone.0164237] [PMID: 27780244]
[82]
Sweeney MD. Blood-brain barrier: From physiology to disease and back. Physiol Rev 2019; 99(1): 21-78.
[PMID: 30280653]
[83]
Li Y, Zhong W, Jiang Z, Tang X. New progress in the approaches for blood–brain barrier protection in acute ischemic stroke. Brain Res Bull 2019; 144: 46-57.
[http://dx.doi.org/10.1016/j.brainresbull.2018.11.006] [PMID: 30448453]
[84]
Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci 2017; 38(7): 1167-86.
[http://dx.doi.org/10.1007/s10072-017-2938-1] [PMID: 28417216]
[85]
Lee SH, Lee JH, Lee HY, Min KJ. Sirtuin signaling in cellular senescence and aging. BMB Rep 2019; 52(1): 24-34.
[http://dx.doi.org/10.5483/BMBRep.2019.52.1.290] [PMID: 30526767]
[86]
Zhang JF, Zhang YL, Wu YC. The role of Sirt1 in ischemic stroke: Pathogenesis and therapeutic strategies. Front Neurosci 2018; 12: 833.
[http://dx.doi.org/10.3389/fnins.2018.00833] [PMID: 30519156]
[87]
Yang R, Shen YJ, Chen M, et al. Quercetin attenuates ischemia reperfusion injury by protecting the blood-brain barrier through Sirt1 in MCAO rats. J Asian Nat Prod Res 2022; 24(3): 278-89.
[http://dx.doi.org/10.1080/10286020.2021.1949302] [PMID: 34292112]
[88]
da Costa JP, Vitorino R, Silva GM, Vogel C, Duarte AC, Rocha-Santos T. A synopsis on aging—Theories, mechanisms and future prospects. Ageing Res Rev 2016; 29: 90-112.
[http://dx.doi.org/10.1016/j.arr.2016.06.005] [PMID: 27353257]
[89]
Wyss-Coray T. Ageing, neurodegeneration and brain rejuvenation. Nature 2016; 539(7628): 180-6.
[http://dx.doi.org/10.1038/nature20411] [PMID: 27830812]
[90]
Tönnies E, Trushina E. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 2017; 57(4): 1105-21.
[http://dx.doi.org/10.3233/JAD-161088] [PMID: 28059794]
[91]
Singh S, Singh TG. Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: An mechanistic approach. Curr Neuropharmacol 2020; 18(10): 918-35.
[http://dx.doi.org/10.2174/1570159X18666200207120949] [PMID: 32031074]
[92]
Lane DJR, Metselaar B, Greenough M, Bush AI, Ayton SJ. Ferroptosis and NRF2: An emerging battlefield in the neurodegeneration of Alzheimer’s disease. Essays Biochem 2021; 65(7): 925-40.
[http://dx.doi.org/10.1042/EBC20210017] [PMID: 34623415]
[93]
Grewal AK, Singh TG, Sharma D, et al. Mechanistic insights and perspectives involved in neuroprotective action of quercetin. Biomed Pharmacother 2021; 140: 111729.
[http://dx.doi.org/10.1016/j.biopha.2021.111729] [PMID: 34044274]
[94]
Wang DM, Li SQ, Wu WL, Zhu XY, Wang Y, Yuan HY. Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer’s disease. Neurochem Res 2014; 39(8): 1533-43.
[http://dx.doi.org/10.1007/s11064-014-1343-x] [PMID: 24893798]
[95]
Chen JC, Ho FM, Chen CP, et al. Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IκB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur J Pharmacol 2005; 521(1-3): 9-20.
[http://dx.doi.org/10.1016/j.ejphar.2005.08.005] [PMID: 16171798]
[96]
Islam MS, Quispe C, Hossain R, et al. Neuropharmacological effects of quercetin: A literature-based review. Front Pharmacol 2021; 12: 665031.
[http://dx.doi.org/10.3389/fphar.2021.665031] [PMID: 34220504]