Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection

Rezaul Islam , Ibrahim Khalil Al-Imran , Mehrukh Zehravi , Sherouk Hussein Sweilam , Mohammad Rakib Mortuza , Jeetendra Kumar Gupta , Thukani Sathanantham Shanmugarajan , Kadirvel Devi , Tanuja Tummala , Mohammed Ali Alshehri , Kalirajan Rajagopal , Mohammed Asiri , Irfan Ahmad , Talha Bin Emran

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (5) : 798 -818.

PDF
Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (5) : 798 -818. DOI: 10.1002/ame2.12551
REVIEW

Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection

Author information +
History +
PDF

Abstract

Background: Neurodegenerative diseases (NDs), including Alzheimer‘s disease, Parkinson‘s disease, and Huntington‘s disease, are complex and challenging due to their intricate pathophysiology and limited treatment options.

Methods: This review systematically sourced articles related to neurodegenerative diseases, neurodegeneration, quercetin, and clinical studies from primary medical databases, including Scopus, PubMed, and Web of Science.

Results: Recent studies have included quercetin to impact the cellular and molecular pathways involved in neurodegeneration. Quercetin, a flavonoid abundant in vegetables and fruits, is gaining attention for its antioxidant, anti-inflammatory, and antiapoptotic properties. It regulates signaling pathways such as nuclear factor-κB (NF-κB), sirtuins, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt). These pathways are essential for cellular survival, inflammation regulation, and apoptosis. Preclinical and clinical studies have shown that quercetin improves symptoms and pathology in neurodegenerative models, indicating promising outcomes.

Conclusions: The study explores the potential of incorporating laboratory research into practical medical treatment, focusing on quercetin‘s neuroprotective effects on NDs and its optimal dosage.

Keywords

neurodegeneration / neurodegenerative diseases / neuroprotection / quercetin / signaling pathways / clinical studies

Cite this article

Download citation ▾
Rezaul Islam, Ibrahim Khalil Al-Imran, Mehrukh Zehravi, Sherouk Hussein Sweilam, Mohammad Rakib Mortuza, Jeetendra Kumar Gupta, Thukani Sathanantham Shanmugarajan, Kadirvel Devi, Tanuja Tummala, Mohammed Ali Alshehri, Kalirajan Rajagopal, Mohammed Asiri, Irfan Ahmad, Talha Bin Emran. Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection. Animal Models and Experimental Medicine, 2025, 8(5): 798-818 DOI:10.1002/ame2.12551

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Pedersen JT, Chen SW, Borg CB, et al. Amyloid-β and α-synuclein decrease the level of metal-catalyzed reactive oxygen species by radical scavenging and redox silencing. J Am Chem Soc. 2016; 138(12): 3966-3969.

[2]

Chan DC. Mitochondria: dynamic organelles in disease, aging, and development. Cell. 2006; 125(7): 1241-1252.

[3]

Zhang Y-w, Thompson R, Zhang H, Xu H. APP processing in Alzheimer's disease. Mol Brain. 2011; 4: 1-13.

[4]

Elumalai P, Lakshmi S. Role of quercetin benefits in neurodegeneration. The Benefits of Natural Products for Neurodegenerative Diseases, Springer Nature; 2016: 229-245.

[5]

Je G, Arora S, Raithatha S, et al. Epidemiology of Parkinson's disease in rural Gujarat, India. Neuroepidemiology. 2021; 55(3): 188-195.

[6]

Uddin MS, Tewari D, Sharma G, et al. Molecular mechanisms of ER stress and UPR in the pathogenesis of Alzheimer's disease. Mol Neurobiol. 2020; 57: 2902-2919.

[7]

Lekoubou A, Echouffo-Tcheugui JB, Kengne AP. Epidemiology of neurodegenerative diseases in sub-Saharan Africa: a systematic review. BMC Public Health. 2014; 14: 1-32.

[8]

Amanzadeh E, Esmaeili A, Rahgozar S, Nourbakhshnia M. Application of quercetin in neurological disorders: from nutrition to nanomedicine. Rev Neurosci. 2019; 30(5): 555-572.

[9]

Suganthy N, Devi KP, Nabavi SF, Braidy N, Nabavi SM. Bioactive effects of quercetin in the central nervous system: focusing on the mechanisms of actions. Biomed Pharmacother. 2016; 84: 892-908.

[10]

Kelly GS. Quercetin. Altern Med Rev. 2011; 16(2): 172-195.

[11]

Vishwas S, Kumar R, Khursheed R, et al. Expanding arsenal against neurodegenerative diseases using quercetin based Nanoformulations: breakthroughs and bottlenecks. Curr Neuropharmacol. 2023; 21(7): 1558-1574.

[12]

Bayazid AB, Lim BO. Quercetin is an active agent in berries against neurodegenerative diseases progression through modulation of Nrf2/HO1. Nutrients. 2022; 14(23): 5132.

[13]

Guo Y, Bruno RS. Endogenous and exogenous mediators of quercetin bioavailability. J Nutr Biochem. 2015; 26(3): 201-210.

[14]

de Boer VC, Dihal AA, van der Woude H, et al. Tissue distribution of quercetin in rats and pigs. J Nutr. 2005; 135(7): 1718-1725.

[15]

Conquer J, Maiani G, Azzini E, Raguzzini A, Holub B. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J Nutr. 1998; 128(3): 593-597.

[16]

Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005; 81(1): 230S-242S.

[17]

Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004; 79(5): 727-747.

[18]

Shanely RA, Knab AM, Nieman DC, Jin F, McAnulty SR, Landram MJ. Quercetin supplementation does not alter antioxidant status in humans. Free Radic Res. 2010; 44(2): 224-231.

[19]

Moon J-H, Tsushida T, Nakahara K, Terao J. Identification of quercetin 3-O-β-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. Free Rad Biol Med. 2001; 30(11): 1274-1285.

[20]

Shirai M, Kawai Y, Yamanishi R, et al. Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent formation of reactive oxygen species in differentiated PC-12 cells. Free Radic Res. 2006; 40(10): 1047-1053.

[21]

Yeh S-L, Yeh C-L, Chan S-T, Chuang C-H. Plasma rich in quercetin metabolites induces G2/M arrest by upregulating PPAR-γ expression in human A549 lung cancer cells. Planta Med. 2011; 77(10): 992-998.

[22]

Ruotolo R, Calani L, Brighenti F, Crozier A, Ottonello S, Del Rio D. Glucuronidation does not suppress the estrogenic activity of quercetin in yeast and human breast cancer cell model systems. Arch Biochem Biophys. 2014; 559: 62-67.

[23]

Cho JM, Chang S-Y, Kim D-B, Needs PW, Jo Y-H, Kim M-J. Effects of physiological quercetin metabolites on interleukin-1β-induced inducible NOS expression. J Nutr Biochem. 2012; 23(11): 1394-1402.

[24]

Fiorani M, Accorsi A, Cantoni O. Human red blood cells as a natural flavonoid reservoir. Free Radic Res. 2003; 37(12): 1331-1338.

[25]

Faria A, Pestana D, Teixeira D, et al. Flavonoid transport across RBE4 cells: a blood-brain barrier model. Cell Mol Biol Lett. 2010; 15(2): 234-241.

[26]

Schaffer S, Halliwell B. Do polyphenols enter the brain and does it matter? Some theoretical and practical considerations. Genes Nutr. 2012; 7: 99-109.

[27]

Ishisaka A, Ichikawa S, Sakakibara H, et al. Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats. Free Rad Biol Med. 2011; 51(7): 1329-1336.

[28]

Huebbe P, Wagner AE, Boesch-Saadatmandi C, Sellmer F, Wolffram S, Rimbach G. Effect of dietary quercetin on brain quercetin levels and the expression of antioxidant and Alzheimer's disease relevant genes in mice. Pharmacol Res. 2010; 61(3): 242-246.

[29]

Das S, Mandal AK, Ghosh A, Panda S, Das N, Sarkar S. Nanoparticulated quercetin in combating age related cerebral oxidative injury. Curr Aging Sci. 2008; 1(3): 169-174.

[30]

Dhawan S, Kapil R, Singh B. Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery. J Pharm Pharmacol. 2011; 63(3): 342-351.

[31]

Ferri P, Angelino D, Gennari L, et al. Enhancement of flavonoid ability to cross the blood-brain barrier of rats by co-administration with α-tocopherol. Food Funct. 2015; 6(2): 394-400.

[32]

Graefe EU, Wittig J, Mueller S, et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol. 2001; 41(5): 492-499.

[33]

Kaşıkcı MB, Bağdatlıoğlu N. Bioavailability of quercetin. Curr Res Nutr Food Sci J. 2016; 4(Special Issue Nutrition in Conference October 2016): 146-151.

[34]

Skaper SD, Facci L, Zusso M, Giusti P. An inflammation-centric view of neurological disease: beyond the neuron. Front Cell Neurosci. 2018; 12: 72.

[35]

McKenzie J, Spielman L, Pointer C, Lowry J, Bajwa E, Lee C. Neuroinflammation as a common mechanism associated with the modifiable risk factors for Alzheimer's and Parkinson's diseases. Curr Aging Sci. 2017; 10: 158-176.

[36]

Otani K, Shichita T. Cerebral sterile inflammation in neurodegenerative diseases. Inflamm Regen. 2020; 40(1): 28.

[37]

Morimoto K, Nakajima K. Role of the immune system in the development of the central nervous system. Front Neurosci. 2019; 13: 468190.

[38]

Mendes MO, Rosa AI, Carvalho AN, et al. Neurotoxic effects of MPTP on mouse cerebral cortex: modulation of neuroinflammation as a neuroprotective strategy. Mol Cell Neurosci. 2019; 96: 1-9.

[39]

Paula P-C, Angelica Maria S-G, Luis C-H, Gloria Patricia C-G. Preventive effect of quercetin in a triple transgenic Alzheimer's disease mice model. Molecules. 2019; 24(12): 2287.

[40]

Wang D-M, Li S-Q, Wu W-L, Zhu X-Y, Wang Y, Yuan H-Y. Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer's disease. Neurochem Res. 2014; 39: 1533-1543.

[41]

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): 50-57.

[42]

Sabogal-Guáqueta AM, Munoz-Manco JI, Ramírez-Pineda JR, Lamprea-Rodriguez M, Osorio E, Cardona-Gómez GP. The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice. Neuropharmacology. 2015; 93: 134-145.

[43]

Yu X, Li Y, Mu X. Effect of quercetin on PC12 Alzheimer's disease cell model induced by Aβ 25-35 and its mechanism based on sirtuin1/Nrf2/HO-1 pathway. Biomed Res Int. 2020; 2020: 1-10.

[44]

Ashrafpour M, Parsaei S, Sepehri H. Quercetin improved spatial memory dysfunctions in rat model of intracerebroventricular streptozotocin-induced sporadic Alzheimer's disease. Natl J Physiol Pharm Pharmacol. 2015; 5: 411-415.

[45]

Nakagawa T, Itoh M, Ohta K, et al. Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer's disease patients. Neuroreport. 2016; 27(9): 671-676.

[46]

Elfiky AM, Mahmoud AA, Elreedy HA, Ibrahim KS, Ghazy MA. Quercetin stimulates the non-amyloidogenic pathway via activation of ADAM10 and ADAM17 gene expression in aluminum chloride-induced Alzheimer's disease rat model. Life Sci. 2021; 285: 119964.

[47]

Li Y, Tian Q, Li Z, Dang M, Lin Y, Hou X. Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats. Drug Dev Res. 2019; 80(6): 837-845.

[48]

Molaei A, Hatami H, Dehghan G, Sadeghian R, Khajehnasiri N. Synergistic effects of quercetin and regular exercise on the recovery of spatial memory and reduction of parameters of oxidative stress in animal model of Alzheimer's disease. EXCLI J. 2020; 19: 596.

[49]

Tong-un T, Muchimapura S, Wattanathorn J, Phachonpai W. Nasal administration of quercetin liposomes improves memory impairment and neurodegeneration in animal model of Alzheimer's disease. Am J Agri Biol Sci. 2010; 5(3): 286-293.

[50]

Amanzadeh Jajin E, Esmaeili A, Rahgozar S, Noorbakhshnia M. Quercetin-conjugated superparamagnetic iron oxide nanoparticles protect AlCl3-induced neurotoxicity in a rat model of Alzheimer's disease via antioxidant genes, APP gene, and miRNA-101. Front Neurosci. 2021; 14: 598617.

[51]

Elreedy HA, Elfiky AM, Mahmoud AA, Ibrahim KS, Ghazy MA. Neuroprotective effect of quercetin through targeting key genes involved in aluminum chloride induced Alzheimer's disease in rats. Egypt J Basic Appl Sci. 2023; 10(1): 174-184.

[52]

Elreedy HA, Elfiky A, Mahmoud A, Salaheldin Ebrahim K, Ghazy M. Effect of quercetin as therapeutic and protective agent in aluminum chloride-induced Alzheimer's disease rats. Egypt J Chem. 2022; 65(4): 633-641.

[53]

Sriraksa N, Wattanathorn J, Muchimapura S, Tiamkao S, Brown K, Chaisiwamongkol K. Cognitive-enhancing effect of quercetin in a rat model of Parkinson's disease induced by 6-hydroxydopamine. Evid Based Complement Alternat Med. 2012; 2012: 1-9.

[54]

El-Horany HE, El-latif RNA, 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): 360-369.

[55]

Wang W-W, Han R, He H-J, et al. Administration of quercetin improves mitochondria quality control and protects the neurons in 6-OHDA-lesioned Parkinson's disease models. Aging (Albany NY). 2021; 13(8): 11738-11751.

[56]

Magalingam KB, Radhakrishnan A, Ramdas P, Haleagrahara N. Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson's disease. J Mol Neurosci. 2015; 55: 609-617.

[57]

Karuppagounder S, Madathil S, Pandey M, Haobam R, Rajamma U, Mohanakumar K. Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson's disease in rats. Neuroscience. 2013; 236: 136-148.

[58]

Lv C, Hong T, Yang Z, et al. Effect of quercetin in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced mouse model of Parkinson's disease. Evid Based Complement Alternat Med. 2012; 2012: 1-6.

[59]

Naghizadeh M, Mirshekar MA, Montazerifar F, et al. Effects of quercetin on spatial memory, hippocampal antioxidant defense and BDNF concentration in a rat model of Parkinson's disease: an electrophysiological study. Avicenna J Phytomed. 2021; 11(6): 599-609.

[60]

Díaz M, Vaamonde L, Dajas F. Assessment of the protective capacity of nanosomes of quercetin in an experimental model of parkinsons disease in the rat. Gen Med (Los Angel). 2015; 3(207): 2.

[61]

Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT. Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson's disease. Free Radic Res. 2005; 39(10): 1119-1125.

[62]

Denny Joseph K, Muralidhara . Combined oral supplementation of fish oil and quercetin enhances neuroprotection in a chronic rotenone rat model: relevance to Parkinson's disease. Neurochem Res. 2015; 40: 894-905.

[63]

Haleagrahara N, Siew CJ, Mitra NK, Kumari M. Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum. Neurosci Lett. 2011; 500(2): 139-143.

[64]

Ekimova I, Plaksina D. Effects of quercetin on neurodegenerative and compensatory processes in the nigrostriatal system in a model of the preclinical stage of Parkinson's disease in rats. Neurosci Behav Physiol. 2017; 47: 1029-1036.

[65]

Zhang ZJ, Cheang LCV, Wang MW, Lee SM-Y. Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish. Int J Mol Med. 2011; 27(2): 195-203.

[66]

Kääriäinen TM, Piltonen M, Ossola B, et al. Lack of robust protective effect of quercetin in two types of 6-hydroxydopamine-induced parkinsonian models in rats and dopaminergic cell cultures. Brain Res. 2008; 1203: 149-159.

[67]

Singh A, Naidu PS, Kulkarni SK. Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition. Pharmacology. 2003; 68(2): 81-88.

[68]

Singh S, Kumar P. Piperine in combination with quercetin halt 6-OHDA induced neurodegeneration in experimental rats: biochemical and neurochemical evidences. Neurosci Res. 2018; 133: 38-47.

[69]

Jain D, Gangshettiwar A. Combination of lycopene, quercetin and poloxamer 188 alleviates anxiety and depression in 3-nitropropionic acid-induced Huntington's disease in rats. J Intercult Ethnopharmacol. 2014; 3(4): 186-191.

[70]

Bhimanwar AA, Ghaisas MM, Shete RV. Silymarin, quercetin and hesperidin combination ameliorate learning and memory deficit in 3 nitro propionic acid induced rat model of Huntington's disease. Available at SSRN 4004056 2022.

[71]

Kuhad A, Singla S, Arora V, Chopra K. Neuroprotective effect of sesamol and quercetin against QA induced neurotoxicity: an experimental paradigm of Huntington's disease. J Neurol Sci. 2013; 333: e149-e150.

[72]

Saadat M, Malekloo R, Davoodi M, et al. Beneficial effects of nano-phytosome of quercetin on inflammatory parameters in mouse model of multiple sclerosis. Eurasian Chem Commun. 2022; 4: 432.

[73]

Ahmadi L, Eskandari N, Ghanadian M, et al. The immunomodulatory aspect of quercetin penta acetate on Th17 cells proliferation and gene expression in multiple sclerosis. Cell Journal (Yakhteh). 2023; 25(2): 110.

[74]

Jiang W, Huang Y, Han N, et al. Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury. Spinal Cord. 2016; 54(8): 592-596.

[75]

Fan H, Tang H-B, Shan L-Q, et al. Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats. J Neuroinflammation. 2019; 16: 1-15.

[76]

Wang Y, Li W, Wang M, et al. Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats. J Cell Biochem. 2018; 119(2): 2298-2306.

[77]

Song Y, Liu J, Zhang F, Zhang J, Shi T, Zeng Z. Antioxidant effect of quercetin against acute spinal cord injury in rats and its correlation with the p38MAPK/iNOS signaling pathway. Life Sci. 2013; 92(24-26): 1215-1221.

[78]

Çiftçi U, Delen E, Vural M, et al. Efficiacy of resveratrol and quercetin after experimental spinal cord injury. Ulus Travma Acil Cerrahi Derg. 2016; 22(5): 423-431.

[79]

Çevik Ö, Erşahin M, Şener TE, et al. Beneficial effects of quercetin on rat urinary bladder after spinal cord injury. J Surg Res. 2013; 183(2): 695-703.

[80]

Schültke E, Griebel R, Juurlink B. Quercetin attenuates inflammatory processes after spinal cord injury in an animal model. Spinal Cord. 2010; 48(12): 857-861.

[81]

Schültke E, Kamencic H, Skihar V, Griebel R, Juurlink B. Quercetin in an animal model of spinal cord compression injury: correlation of treatment duration with recovery of motor function. Spinal Cord. 2010; 48(2): 112-117.

[82]

Liu J-b, Tang T-s, Yang H-l. Antioxidation of quercetin against spinal cord injury in rats. Chin J Traumatol. 2006; 9(5): 303-307.

[83]

Schültke E, Griebel R, Juurlink B. Quercetin administration after spinal cord trauma changes S-100β levels. Can J Neurol Sci. 2010; 37(2): 223-228.

[84]

Keyhanifard M, Helali H, Gholami M, Akbari M, Omraninava M, Mohammadi H. Quercetin in combination with hyperbaric oxygen therapy synergistically attenuates damage progression in traumatic spinal cord injury in a rat model. J Chem Neuroanat. 2023; 128: 102231.

[85]

Huang Y, Zhang X, Huang Q, et al. Quercetin enhances survival and axonal regeneration of motoneurons after spinal root avulsion and reimplantation: experiments in a rat model of brachial plexus avulsion. Inflamm Regen. 2022; 42(1): 56.

[86]

Firgany AE-DL, Sarhan NR. Quercetin mitigates monosodium glutamate-induced excitotoxicity of the spinal cord motoneurons in aged rats via p38 MAPK inhibition. Acta Histochem. 2020; 122(5): 151554.

[87]

Khan A, Ali T, Rehman SU, et al. Neuroprotective effect of quercetin against the detrimental effects of LPS in the adult mouse brain. Front Pharmacol. 2018; 9: 386229.

[88]

Suematsu N, Hosoda M, Fujimori K. Protective effects of quercetin against hydrogen peroxide-induced apoptosis in human neuronal SH-SY5Y cells. Neurosci Lett. 2011; 504(3): 223-227.

[89]

Denny JK. Enhanced neuroprotective effect of fish oil in combination with quercetin against 3-nitropropionic acid induced oxidative stress in rat brain. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013; 40: 83-92.

[90]

Jain J, Hasan W, Biswas P, Yadav RS, Jat D. Neuroprotective effect of quercetin against rotenone-induced neuroinflammation and alterations in mice behavior. J Biochem Mol Toxicol. 2022; 36(10): e23165.

[91]

Gupta R, Shukla RK, Chandravanshi LP, et al. Protective role of quercetin in cadmium-induced cholinergic dysfunctions in rat brain by modulating mitochondrial integrity and MAP kinase signaling. Mol Neurobiol. 2017; 54: 4560-4583.

[92]

Beckmann DV, Carvalho FB, Mazzanti CM, et al. Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide. Life Sci. 2014; 103(2): 79-87.

[93]

Kumar A, Goyal R. Quercetin protects against acute immobilization stress-induced behaviors and biochemical alterations in mice. J Med Food. 2008; 11(3): 469-473.

[94]

Xi J, Zhang B, Luo F, Liu J, Yang T. Quercetin protects neuroblastoma SH-SY5Y cells against oxidative stress by inhibiting expression of Krüppel-like factor 4. Neurosci Lett. 2012; 527(2): 115-120.

[95]

Ebrahimi A, Parivar K, Roodbari NH-E, Eidi A. Investigating the effect of quercetin on disease progression and recovery process in experimental autoimmune encephalomyelitis (EAE's) rats. 2023.

[96]

Ebrahimi A, Parivar K, Roodbari NH-E, Eidi A. Treatment with quercetin increases Nrf2 expression and neuronal differentiation of sub ventricular zone derived neural progenitor stem cells in adult rats. Mol Biol Rep. 2023; 50(10): 8163-8175.

[97]

Carvalho FB, Gutierres JM, Beckmann D, et al. Quercetin treatment regulates the Na+, K+-ATPase activity, peripheral cholinergic enzymes, and oxidative stress in a rat model of demyelination. Nutr Res. 2018; 55: 45-56.

[98]

Naeimi R, Baradaran S, Ashrafpour M, Moghadamnia AA, Ghasemi-Kasman M. Querectin improves myelin repair of optic chiasm in lyolecithin-induced focal demyelination model. Biomed Pharmacother. 2018; 101: 485-493.

[99]

Du G, Zhao Z, Chen Y, et al. Quercetin attenuates neuronal autophagy and apoptosis in rat traumatic brain injury model via activation of PI3K/Akt signaling pathway. Neurol Res. 2016; 38(11): 1012-1019.

[100]

Kale A, Pişkin Ö, Baş Y, et al. Neuroprotective effects of quercetin on radiation-induced brain injury in rats. J Radiat Res. 2018; 59(4): 404-410.

[101]

Regitz C, Marie Dußling L, Wenzel U. Amyloid-beta (A β1-42)-induced paralysis in C aenorhabditis elegans is inhibited by the polyphenol quercetin through activation of protein degradation pathways. Mol Nutr Food Res. 2014; 58(10): 1931-1940.

[102]

David AVA, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacog Rev. 2016; 10(20): 84.

[103]

Khan TK, Nelson TJ, Verma VA, Wender PA, Alkon DL. A cellular model of Alzheimer's disease therapeutic efficacy: PKC activation reverses Aβ-induced biomarker abnormality on cultured fibroblasts. Neurobiol Dis. 2009; 34(2): 332-339.

[104]

Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Flavonols and flavones as BACE-1 inhibitors: structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features. Biochim Biophys Acta-Gen Subj. 2008; 1780(5): 819-825.

[105]

Dal Belo CA, Lucho APB, Vinadé L, et al. In vitro antiophidian mechanisms of Hypericum brasiliense choisy standardized extract: quercetin-dependent neuroprotection. Biomed Res Int. 2013; 2013: 1-6.

[106]

Davis JM, Murphy EA, Carmichael MD. Effects of the dietary flavonoid quercetin upon performance and health. Curr Sports Med Rep. 2009; 8(4): 206-213.

[107]

West S, Bhugra P. Emerging drug targets for Aβ and tau in Alzheimer's disease: a systematic review. Br J Clin Pharmacol. 2015; 80(2): 221-234.

[108]

Sastre M, Klockgether T, Heneka MT. Contribution of inflammatory processes to Alzheimer's disease: molecular mechanisms. Int J Dev Neurosci. 2006; 24(2-3): 167-176.

[109]

Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA. Protective effect of quercetin in primary neurons against Aβ (1-42): relevance to Alzheimer's disease. J Nutr Biochem. 2009; 20(4): 269-275.

[110]

Keddy PG, Dunlop K, Warford J, et al. Neuroprotective and anti-inflammatory effects of the flavonoid-enriched fraction AF4 in a mouse model of hypoxic-ischemic brain injury. PLoS One. 2012; 7(12): e51324.

[111]

Tota S, Awasthi H, Kamat PK, Nath C, Hanif K. Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice. Behav Brain Res. 2010; 209(1): 73-79.

[112]

Ossola B, Kääriäinen TM, Männistö PT. The multiple faces of quercetin in neuroprotection. Expert Opin Drug Saf. 2009; 8(4): 397-409.

[113]

Khan H, Ullah H, Aschner M, Cheang WS, Akkol EK. Neuroprotective effects of quercetin in Alzheimer's disease. Biomolecules. 2019; 10(1): 59.

[114]

Ay M, Luo J, Langley M, et al. Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson's disease. J Neurochem. 2017; 141(5): 766-782.

[115]

Shelat PB, Chalimoniuk M, Wang JH, et al. Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. J Neurochem. 2008; 106(1): 45-55.

[116]

Barreca D, Bellocco E, DOnofrio G, et al. Neuroprotective effects of quercetin: from chemistry to medicine. CNS Neurol Disord Drug Targets. 2016; 15(8): 964-975.

[117]

Godoy JA, Lindsay CB, Quintanilla RA, Carvajal FJ, Cerpa W, Inestrosa NC. Quercetin exerts differential neuroprotective effects against H 2 O 2 and Aβ aggregates in hippocampal neurons: the role of mitochondria. Mol Neurobiol. 2017; 54: 7116-7128.

[118]

Chen T-J, Jeng J-Y, Lin C-W, Wu C-Y, Chen Y-C. Quercetin inhibition of ROS-dependent and-independent apoptosis in rat glioma C6 cells. Toxicology. 2006; 223(1-2): 113-126.

[119]

Mehta V, Parashar A, Udayabanu M. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress. Physiol Behav. 2017; 171: 69-78.

[120]

Unsal C, Kanter M, Aktas C, Erboga M. Role of quercetin in cadmium-induced oxidative stress, neuronal damage, and apoptosis in rats. Toxicol Ind Health. 2015; 31(12): 1106-1115.

[121]

Shim JS, Kim HG, Ju MS, Choi JG, Jeong SY, Oh MS. Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease. J Ethnopharmacol. 2009; 126(2): 361-365.

[122]

Korczyn AD. Dementia in Parkinson's disease. J Neurol. 2001; 248: III1-III4.

[123]

Haleagrahara N, Siew CJ, Ponnusamy K. Effect of quercetin and desferrioxamine on 6-hydroxydopamine (6-OHDA) induced neurotoxicity in striatum of rats. J Toxicol Sci. 2013; 38(1): 25-33.

[124]

Moshahid Khan M, Raza SS, Javed H, et al. Rutin protects dopaminergic neurons from oxidative stress in an animal model of Parkinson's disease. Neurotox Res. 2012; 22: 1-15.

[125]

Batiha GE-S, Beshbishy AM, Ikram M, et al. The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: quercetin. Foods. 2020; 9(3): 374.

[126]

Kumar R, Kumar R, Khurana N, et al. Improved neuroprotective activity of Fisetin through SNEDDS in ameliorating the behavioral alterations produced in rotenone-induced Parkinson's model. Environ Sci Pollut Res. 2022; 29(33): 50488-50499.

[127]

Singh S, Jamwal S, Kumar P. Neuroprotective potential of quercetin in combination with piperine against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced neurotoxicity. Neural Regen Res. 2017; 12(7): 1137-1144.

[128]

Sharma D, Wani W, Sunkaria A, et al. Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus. Neuroscience. 2016; 324: 163-176.

[129]

Walker FO. Huntington's disease. Lancet. 2007; 369(9557): 218-228.

[130]

Sandhir R, Mehrotra A. Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid: implications in Huntington's disease. Biochim Biophys Acta (BBA)-Mol Basis Dis. 2013; 1832(3): 421-430.

[131]

Chakraborty J, Singh R, Dutta D, Naskar A, Rajamma U, Mohanakumar KP. Quercetin improves behavioral deficiencies, restores astrocytes and microglia, and reduces serotonin metabolism in 3-nitropropionic acid-induced rat model of Huntington's disease. CNS Neurosci Ther. 2014; 20(1): 10-19.

[132]

Sternberg Z, Chadha K, Lieberman A, et al. Quercetin and interferon-β modulate immune response (s) in peripheral blood mononuclear cells isolated from multiple sclerosis patients. J Neuroimmunol. 2008; 205(1-2): 142-147.

[133]

Chen Y, Zhang M, Li W, et al. Drug repurposing based on the similarity gene expression signatures to explore for potential indications of quercetin: a case study of multiple sclerosis. Front Chem. 2023; 11: 1250043.

[134]

Mirzazadeh E, Khezri S, Abtahi Froushani SM. Effects of quercetin on improving the damage caused by free radicals in the rat models of multiple sclerosis. Iran South Med J. 2019; 22(1): 1-15.

[135]

Feldman EL, Goutman SA, Petri S, et al. Amyotrophic lateral sclerosis. Lancet. 2022; 400(10360): 1363-1380.

[136]

Jin T, Zhang Y, Botchway BO, Huang M, Lu Q, Liu X. Quercetin activates the Sestrin2/AMPK/SIRT1 axis to improve amyotrophic lateral sclerosis. Biomed Pharmacother. 2023; 161: 114515.

[137]

Ip P, Sharda PR, Cunningham A, Chakrabartty S, Pande V, Chakrabartty A. Quercitrin and quercetin 3-β-d-glucoside as chemical chaperones for the A4V SOD1 ALS-causing mutant. Protein Eng Des Select. 2017; 30(6): 431-440.

[138]

Ahmed MS, Hung W-Y, Zu JS, Hockberger P, Siddique T. Increased reactive oxygen species in familial amyotrophic lateral sclerosis with mutations in SOD1. J Neurol Sci. 2000; 176(2): 88-94.

[139]

Lazo-Gomez R, Tapia R. Quercetin prevents spinal motor neuron degeneration induced by chronic excitotoxic stimulus by a sirtuin 1-dependent mechanism. Transl Neurodegen. 2017; 6: 1-14.

[140]

Bhatia NK, Modi P, Sharma S, Deep S. Quercetin and baicalein act as potent antiamyloidogenic and fibril destabilizing agents for SOD1 fibrils. ACS Chem Neurosci. 2020; 11(8): 1129-1138.

[141]

Wang X, Fu Y, Botchway BO, et al. Quercetin can improve spinal cord injury by regulating the mTOR signaling pathway. Front Neurol. 2022; 13: 905640.

[142]

Wang Y, Xiong M, Wang M, Chen H, Li W, Zhou X. Quercetin promotes locomotor function recovery and axonal regeneration through induction of autophagy after spinal cord injury. Clin Exp Pharmacol Physiol. 2021; 48(12): 1642-1652.

[143]

Danielsen SA, Eide PW, Nesbakken A, Guren T, Leithe E, Lothe RA. Portrait of the PI3K/AKT pathway in colorectal cancer. Biochim Biophys Acta (BBA)-Rev Cancer. 2015; 1855(1): 104-121.

[144]

Xia S-F, Xie Z-X, Qiao Y, et al. Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress. Physiol Behav. 2015; 138: 325-331.

[145]

Chang H-C, Yang Y-R, Wang PS, Wang R-Y. Quercetin enhances exercise-mediated neuroprotective effects in brain ischemic rats. Med Sci Sports Exerc. 2014; 46(10): 1908-1916.

[146]

Chen L, Sun L, Liu Z, Wang H, Xu C. Protection afforded by quercetin against H2O2-induced apoptosis on PC12 cells via activating PI3K/Akt signal pathway. J Recept Signal Transduct. 2016; 36(1): 98-102.

[147]

Gräff J, Kahn M, Samiei A, et al. A dietary regimen of caloric restriction or pharmacological activation of SIRT1 to delay the onset of neurodegeneration. J Neurosci. 2013; 33(21): 8951-8960.

[148]

Tchantchou F, Lacor PN, Cao Z, et al. Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. J Alzheimers Dis. 2009; 18(4): 787-798.

[149]

Qin W, Yang T, Ho L, et al. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem. 2006; 281(31): 21745-21754.

[150]

de Boer VC, de Goffau MC, Arts IC, Hollman PC, Keijer J. SIRT1 stimulation by polyphenols is affected by their stability and metabolism. Mech Ageing Dev. 2006; 127(7): 618-627.

[151]

Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA, Dijkstra CD. Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study. Biochem Pharmacol. 2003; 65(5): 877-885.

[152]

Leyton L, Hott M, Acuña F, et al. Nutraceutical activators of AMPK/Sirt1 axis inhibit viral production and protect neurons from neurodegenerative events triggered during HSV-1 infection. Virus Res. 2015; 205: 63-72.

[153]

Gan L, Johnson JA. Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim Biophys Acta (BBA)-Mol Basis Dis. 2014; 1842(8): 1208-1218.

[154]

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): 2755-2761.

[155]

Sharma V, Kaur A, Singh TG. Counteracting role of nuclear factor erythroid 2-related factor 2 pathway in Alzheimer's disease. Biomed Pharmacother. 2020; 129: 110373.

[156]

Halliwell B. Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? Arch Biochem Biophys. 2008; 476(2): 107-112.

[157]

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: 303-311.

[158]

Tanigawa S, Fujii M, Hou D-X. Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Rad Biol Med. 2007; 42(11): 1690-1703.

[159]

Dong F, Wang S, Wang Y, et al. Quercetin ameliorates learning and memory via the Nrf2-ARE signaling pathway in d-galactose-induced neurotoxicity in mice. Biochem Biophys Res Commun. 2017; 491(3): 636-641.

[160]

Idriss HT, Naismith JH. TNFα and the TNF receptor superfamily: structure-function relationship (s). Microsc Res Tech. 2000; 50(3): 184-195.

[161]

Zhang M, Swarts SG, Yin L, et al. Antioxidant properties of quercetin. Springer; 2011: 283-289.

[162]

Bureau G, Longpré F, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res. 2008; 86(2): 403-410.

[163]

Sharma BR, Gautam LNS, Adhikari D, Karki R. A comprehensive review on chemical profiling of Nelumbo nucifera: potential for drug development. Phytother Res. 2017; 31(1): 3-26.

[164]

Testa G, Gamba P, Badilli U, et al. Loading into nanoparticles improves quercetin's efficacy in preventing neuroinflammation induced by oxysterols. PLoS One. 2014; 9(5): e96795.

[165]

Lavoie S, Chen Y, Dalton TP, et al. Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit. J Neurochem. 2009; 108(6): 1410-1422.

[166]

van Meeteren ME, Hendriks JJ, Dijkstra CD, van Tol EA. Dietary compounds prevent oxidative damage and nitric oxide production by cells involved in demyelinating disease. Biochem Pharmacol. 2004; 67(5): 967-975.

[167]

Sabapathy K. Role of the JNK pathway in human diseases. Prog Mol Biol Transl Sci. 2012; 106: 145-169.

[168]

Sharma VK, Singh TG. Chronic stress and diabetes mellitus: interwoven pathologies. Curr Diabetes Rev. 2020; 16(6): 546-556.

[169]

Resnick L, Fennell M. Targeting JNK3 for the treatment of neurodegenerative disorders. Drug Discov Today. 2004; 9(21): 932-939.

[170]

Kumar A, Singh UK, Kini SG, et al. JNK pathway signaling: a novel and smarter therapeutic targets for various biological diseases. Future Med Chem. 2015; 7(15): 2065-2086.

[171]

Ishikawa Y, Kitamura M. Anti-apoptotic effect of quercetin: intervention in the JNK-and ERK-mediated apoptotic pathways. Kidney Int. 2000; 58(3): 1078-1087.

[172]

Verheij M, Bose R, Hua Lin X, et al. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature. 1996; 380(6569): 75-79.

[173]

Uchida K, Shiraishi M, Naito Y, Torii Y, Nakamura Y, Osawa T. Activation of stress signaling pathways by the end product of lipid peroxidation: 4-hydroxy-2-nonenal is a potential inducer of intracellular peroxide production. J Biol Chem. 1999; 274(4): 2234-2242.

[174]

Park J-Y, Lim M-S, Kim S-I, et al. Quercetin-3-O-β-D-glucuronide suppresses lipopolysaccharide-induced JNK and ERK phosphorylation in LPS-challenged RAW264. 7 cells. Biomol Therapeut. 2016; 24(6): 610-615.

[175]

Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN. Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005; 46(6): 1239-1247.

[176]

Ng CJ, Bourquard N, Grijalva V, et al. Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. J Biol Chem. 2006; 281(40): 29491-29500.

[177]

Marsillach J, Mackness B, Mackness M, et al. Immunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues. Free Rad Biol Med. 2008; 45(2): 146-157.

[178]

Giordano G, Cole TB, Furlong CE, Costa LG. Paraoxonase 2 (PON2) in the mouse central nervous system: a neuroprotective role? Toxicol Appl Pharmacol. 2011; 256(3): 369-378.

[179]

Devarajan A, Bourquard N, Hama S, et al. Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis. Antioxid Redox Signal. 2011; 14(3): 341-351.

[180]

Giordano G, Tait L, Furlong C, Cole T, Kavanagh T, Costa LG. Gender differences in brain susceptibility to oxidative stress are mediated by levels of paraoxonase-2 expression. Free Rad Biol Med. 2013; 58: 98-108.

[181]

Altenhöfer S, Witte I, Teiber JF, et al. One enzyme, two functions: PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity. J Biol Chem. 2010; 285(32): 24398-24403.

[182]

Costa LG, de Laat R, Dao K, Pellacani C, Cole TB, Furlong CE. Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection. Neurotoxicology. 2014; 43: 3-9.

[183]

Rosenblat M, Draganov D, Watson CE, Bisgaier CL, La Du BN, Aviram M. Mouse macrophage paraoxonase 2 activity is increased whereas cellular paraoxonase 3 activity is decreased under oxidative stress. Arterioscler Thromb Vasc Biol. 2003; 23(3): 468-474.

[184]

Horke S, Witte I, Wilgenbus P, Krüger M, Strand D, Förstermann U. Paraoxonase-2 reduces oxidative stress in vascular cells and decreases endoplasmic reticulum stress-induced caspase activation. Circulation. 2007; 115(15): 2055-2064.

[185]

Costa LG, Garrick J, Roque PJ, Pellacani C. Nutraceuticals in CNS diseases: potential mechanisms of neuroprotection. Nutraceuticals. 2016; 3-13.

[186]

Costa LG, Tait L, de Laat R, et al. Modulation of paraoxonase 2 (PON2) in mouse brain by the polyphenol quercetin: a mechanism of neuroprotection? Neurochem Res. 2013; 38: 1809-1818.

[187]

Chang Y-F, Hsu Y-C, Hung H-F, et al. Quercetin induces oxidative stress and potentiates the apoptotic action of 2-methoxyestradiol in human hepatoma cells. Nutr Cancer. 2009; 61(5): 735-745.

[188]

Nicolas CS, Amici M, Bortolotto ZA, et al. The role of JAK-STAT signaling within the CNS. Jak-Stat. 2013; 2(1): e22925.

[189]

Yan Z, Gibson SA, Buckley JA, Qin H, Benveniste EN. Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases. Clin Immunol. 2018; 189: 4-13.

[190]

Jain M, Singh MK, Shyam H, et al. Role of JAK/STAT in the neuroinflammation and its association with neurological disorders. Ann Neurosci. 2021; 28(3-4): 191-200.

[191]

Ghosh A, Sarkar S, Mandal AK, Das N. Neuroprotective role of nanoencapsulated quercetin in combating ischemia-reperfusion induced neuronal damage in young and aged rats. PLoS One. 2013; 8(4): e57735.

[192]

Chen T, Zhang X, Zhu G, et al. Quercetin inhibits TNF-α induced HUVECs apoptosis and inflammation via downregulating NF-kB and AP-1 signaling pathway in vitro. Medicine. 2020; 99(38): e22241.

[193]

Grewal AK, Singh TG, Sharma D, et al. Mechanistic insights and perspectives involved in neuroprotective action of quercetin. Biomed Pharmacother. 2021; 140: 111729.

[194]

Han X, Xu T, Fang Q, et al. Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy. Redox Biol. 2021; 44: 102010.

[195]

Anderson FL, Biggs KE, Rankin BE, Havrda MC. NLRP3 inflammasome in neurodegenerative disease. Transl Res. 2023; 252: 21-33.

[196]

Zhan X, Li Q, Xu G, Xiao X, Bai Z. The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors. Front Immunol. 2023; 13: 1109938.

[197]

Cui Z, Zhao X, Amevor FK, et al. Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism. Front Immunol. 2022; 13: 943321.

[198]

Chen Y, Peng F, Xing Z, Chen J, Peng C, Li D. Beneficial effects of natural flavonoids on neuroinflammation. Front Immunol. 2022; 13: 1006434.

[199]

Costa LG, Garrick JM, Roquè PJ, Pellacani C. Mechanisms of neuroprotection by quercetin: counteracting oxidative stress and more. Oxidative Med Cell Longev. 2016; 2016: 2986796.

[200]

Caruana M, Cauchi R, Vassallo N. Putative role of red wine polyphenols against brain pathology in Alzheimer's and Parkinson's disease. Front Nutr. 2016; 3: 31.

[201]

Jantan I, Ahmad W, Bukhari SNA. Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. Front Plant Sci. 2015; 6: 158994.

[202]

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 Rad Biol Med. 2010; 49(5): 738-747.

[203]

Waseem M, Parvez S. Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin. Protoplasma. 2016; 253: 417-430.

[204]

Bavithra S, Selvakumar K, Pratheepa Kumari R, Krishnamoorthy G, Venkataraman P, Arunakaran J. Polychlorinated biphenyl (PCBs)-induced oxidative stress plays a critical role on cerebellar dopaminergic receptor expression: ameliorative role of quercetin. Neurotox Res. 2012; 21: 149-159.

[205]

Boesch-Saadatmandi C, Loboda A, Wagner AE, et al. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155. J Nutr Biochem. 2011; 22(3): 293-299.

[206]

Barcelos GRM, Grotto D, Serpeloni JM, et al. Protective properties of quercetin against DNA damage and oxidative stress induced by methylmercury in rats. Arch Toxicol. 2011; 85: 1151-1157.

[207]

Sachdeva S, Pant SC, Kushwaha P, Bhargava R, Flora SJ. Sodium tungstate induced neurological alterations in rat brain regions and their response to antioxidants. Food Chem Toxicol. 2015; 82: 64-71.

[208]

Lakroun Z, Kebieche M, Lahouel A, Zama D, Desor F, Soulimani R. Oxidative stress and brain mitochondria swelling induced by endosulfan and protective role of quercetin in rat. Environ Sci Pollut Res. 2015; 22: 7776-7781.

[209]

Zhang Y, Yi B, Ma J, et al. Quercetin promotes neuronal and behavioral recovery by suppressing inflammatory response and apoptosis in a rat model of intracerebral hemorrhage. Neurochem Res. 2015; 40: 195-203.

[210]

Arikan S, Ersan I, Karaca T, et al. Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model. Arq Bras Oftalmol. 2015; 78: 100-104.

[211]

Joseph KD. Enhanced neuroprotective effect of fish oil in combination with quercetin against 3-nitropropionic acid induced oxidative stress in rat brain. Progr Neuro-Psychopharmacol Biol Psych. 2013; 40: 83-92.

[212]

Boyina HK, Geethakhrishnan SL, Panuganti S, et al. In silico and in vivo studies on quercetin as potential anti-Parkinson agent. GeNeDis 2018 Genet Neurodegen. 2020; 2020: 1-11.

[213]

Figueira I, Menezes R, Macedo D, Costa I, Nunes dos Santos C. Polyphenols beyond barriers: a glimpse into the brain. Curr Neuropharmacol. 2017; 15(4): 562-594.

[214]

Khan MTH, Orhan I, Şenol F, et al. Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies. Chem Biol Interact. 2009; 181(3): 383-389.

[215]

Sun D, Li N, Zhang W, et al. Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer's disease. Colloids Surf B Biointerfaces. 2016; 148: 116-129.

[216]

Men K, Duan X, Wei Wei X, et al. Nanoparticle-delivered quercetin for cancer therapy. Anti Cancer Agents Med Chem. 2014; 14(6): 826-832.

[217]

Zhang X-W, Chen J-Y, Ouyang D, Lu J-H. Quercetin in animal models of Alzheimer's disease: a systematic review of preclinical studies. Int J Mol Sci. 2020; 21(2): 493.

[218]

Olson CA, Thornton JA, Adam GE, Lieberman HR. Effects of 2 adenosine antagonists, quercetin and caffeine, on vigilance and mood. J Clin Psychopharmacol. 2010; 30(5): 573-578.

[219]

Broman-Fulks JJ, Canu WH, Trout KL, Nieman DC. The effects of quercetin supplementation on cognitive functioning in a community sample: a randomized, placebo-controlled trial. Ther Adv Psychopharmacol. 2012; 2(4): 131-138.

[220]

Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015; 14(4): 644-658.

[221]

Gonzales MM, Garbarino V, Zilli EM, et al. Senolytic therapy to modulate the progression of Alzheimer's disease (SToMP-AD): a pilot clinical trial. J Prev Alzheimers Dis. 2022; 9: 1-8.

[222]

Nishihira J, Nishimura M, Kurimoto M, et al. The effect of 24-week continuous intake of quercetin-rich onion on age-related cognitive decline in healthy elderly people: a randomized, double-blind, placebo-controlled, parallel-group comparative clinical trial. J Clin Biochem Nutr. 2021; 69(2): 203-215.

RIGHTS & PERMISSIONS

2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

AI Summary AI Mindmap
PDF

6

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/