Quercetin in brain diseases: Potential and limits

Neurochemistry International

Volumn 89, Issue , 2015, Pages 140-148

  Dajas, Federico ^a   Abin Carriquiry, Juan Andrés ^a   Arredondo, Florencia ^a   Blasina, Fernanda ^a   Echeverry, Carolina ^a   Martínez, Marcela ^a   Rivera, Felicia ^a   Vaamonde, Lucía ^a  

^a INSTITUTO DE INVESTIGACIONES BIOLÓGICAS CLEMENTE ESTABLE   (Uruguay)

Author keywords

Brain; Flavonoids; Neuroprotection; Nutraceuticals; Quercetin

Indexed keywords

GLUTATHIONE; HYDROGEN PEROXIDE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; QUERCETIN; SCAVENGER; SIRTUIN 1; STRESS ACTIVATED PROTEIN KINASE; TRANSCRIPTION FACTOR NRF2; ANTIOXIDANT; FLAVONOID; NEUROPROTECTIVE AGENT; REACTIVE OXYGEN METABOLITE;

ANTIOXIDANT ACTIVITY; ANTIOXIDANT RESPONSIVE ELEMENT; APOPTOSIS; ARTICLE; ASTROCYTE; BRAIN DISEASE; BRAIN ISCHEMIA; CELL SURVIVAL; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG HALF LIFE; GENE EXPRESSION; HEMODYNAMIC MONITORING; HUMAN; INTRACELLULAR SIGNALING; LONG TERM CARE; MICROGLIA; MIDDLE CEREBRAL ARTERY OCCLUSION; NERVE CELL CULTURE; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; OXIDATION REDUCTION POTENTIAL; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; PRIORITY JOURNAL; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN DISEASES; DRUG EFFECTS; METABOLISM; PHYSIOLOGY;

ANIMALS; ANTIOXIDANTS; BRAIN DISEASES; FLAVONOIDS; HUMANS; NEUROPROTECTIVE AGENTS; OXIDATIVE STRESS; QUERCETIN; REACTIVE OXYGEN SPECIES;

EID: 84942292653     PISSN: 01970186     EISSN: 18729754     Source Type: Journal    
DOI: 10.1016/j.neuint.2015.07.002     Document Type: Article

References (157)

1. M.A. Ansari, H.M. Abdul, G. Joshi, W.O. Opii, and D.A. Butterfield Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer's disease J. Nutr. Biochem. 20 2009 269 275
2. Y. Aoki, M. Tamura, Y. Itoh, and Y. Ukai Cerebroprotective action of a Na+/Ca2+ channel blocker NS-7. I. Effect on the cerebral infarction and edema at the acute stage of permanent middle cerebral artery occlusion in rats Brain Res. 890 2001 162 169
3. F. Arredondo, C. Echeverry, J.A. Abin-Carriquiry, F. Blasina, K. Antúnez, D.P. Jones, Y.-M. Go, Y.-L. Liang, and F. Dajas After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult Free Radic. Biol. Med. 49 2010 738 747
4. F. Arredondo, C. Echeverry, F. Blasina, L. Vaamonde, M. Díaz, F. Rivera, M. Martínez, J.A. Abin-Carriquiry, and F. Dajas Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease 2015 Elsevier
5. I.C.W. Arts, A.L.A. Sesink, M. Faassen-Peters, and P.C.H. Hollman The type of sugar moiety is a major determinant of the small intestinal uptake and subsequent biliary excretion of dietary quercetin glycosides Br. J. Nutr. 91 2004 841 847
6. A.A. Aziz, C.A. Edwards, M.E. Lean, and A. Crozier Absorption and excretion of conjugated flavonols, including quercetin-4′-O-beta-glucoside and isorhamnetin-4′-O-beta-glucoside by human volunteers after the consumption of onions Free Radic. Res. 29 1998 257 269
7. J.S. Bains, and C.A. Shaw Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death Brain Res. Brain Res. Rev. 25 1997 335 358
8. Y. Bandaruk, R. Mukai, and J. Terao Cellular uptake of quercetin and luteolin and their effects on monoamine oxidase-A in human neuroblastoma SH-SY5Y cells Toxicol. Rep. 1 2014 639 649
9. J. Bieger, R. Cermak, R. Blank, V.C.J. de Boer, P.C.H. Hollman, J. Kamphues, and S. Wolffram Tissue distribution of quercetin in pigs after long-term dietary supplementation J. Nutr. 138 2008 1417 1420
10. S.C. Bischoff Quercetin: potentials in the prevention and therapy of disease Curr. Opin. Clin. Nutr. Metab. Care 11 2008 733 740
11. G. Bjelakovic, and C. Gluud Surviving antioxidant supplements J. Natl. Cancer Inst. 99 2007 742 743
12. A.W. Boots, N. Kubben, G.R.M.M. Haenen, and A. Bast Oxidized quercetin reacts with thiols rather than with ascorbate: implication for quercetin supplementation Biochem. Biophys. Res. Commun. 308 2003 560 565
13. W. Bors, W. Heller, C. Michel, and M. Saran Radical chemistry of flavonoid antioxidants Adv. Exp. Med. Biol. 264 1990 165 170
14. J. Bournival, P. Quessy, and M.-G. Martinoli Protective effects of resveratrol and quercetin against MPP+ -induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons Cell. Mol. Neurobiol. 29 2009 1169 1180
15. A. Brunet, S.R. Datta, and M.E. Greenberg Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway Curr. Opin. Neurobiol. 11 2001 297 305
16. G. Cainelli, C. Angeloni, R. Cervellati, P. Galletti, D. Giacomini, S. Hrelia, and R. Sinisi New polyphenolic beta-lactams with antioxidant activity Chem. Biodivers. 5 2008 811 829
17. X. Cao, and J.W. Phillis alpha-Phenyl-tert-butyl-nitrone reduces cortical infarct and edema in rats subjected to focal ischemia Brain Res. 644 1994 267 272
18. C. Carrasco-Pozo, M.L. Mizgier, H. Speisky, and M. Gotteland Differential protective effects of quercetin, resveratrol, rutin and epigallocatechin gallate against mitochondrial dysfunction induced by indomethacin in Caco-2 cells Chem. Biol. Interact. 195 2012 199 205
19. J. Chakraborty, R. Singh, D. Dutta, A. Naskar, U. Rajamma, and K.P. Mohanakumar 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. 20 2014 10 19
20. H. Chang, M. Mi, W. Ling, J. Zhu, Q. Zhang, N. Wei, Y. Zhou, Y. Tang, and J. Yuan Structurally related cytotoxic effects of flavonoids on human cancer cells in vitro Arch. Pharm. Res. 31 2008 1137 1144
21. C. Chen, J. Zhou, and C. Ji Quercetin: a potential drug to reverse multidrug resistance Life Sci. 87 2010 333 338
22. J.-C. Chen, F.-M. Ho, Lee Chao Pei-Dawn, C.-P. Chen, K.-C.G. Jeng, H.-B. Hsu, S.-T. Lee, Tung Wu Wen, and W.-W. Lin Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia Eur. J. Pharmacol. 521 2005 9 20
23. P.-Y. Chen, Y.-R. Ho, M.-J. Wu, S.-P. Huang, P.-K. Chen, M.-H. Tai, C.-T. Ho, and J.-H. Yen Cytoprotective effects of fisetin against hypoxia-induced cell death in PC12 cells Food Funct. 6 2015 286 295
24. D.D. Clarke, and L. Sokoloff Circulation and Energy Metabolism of the Brain 1999
25. J.A. Conquer, G. Maiani, E. Azzini, A. Raguzzini, and B.J. Holub Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects J. Nutr. 128 1998 593 597
26. N. Cotelle Role of flavonoids in oxidative stress Curr. Top. Med. Chem. 1 2001 569 590
27. Q. Dai, A.R. Borenstein, Y. Wu, J.C. Jackson, and E.B. Larson Fruit and vegetable juices and Alzheimer's disease: the Kame Project Am. J. Med. 119 2006 751 759
28. F. Dajas Life or death: neuroprotective and anticancer effects of quercetin J. Ethnopharmacol. 143 2012 383 396
29. F. Dajas, F. Rivera, F. Blasina, F. Arredondo, C. Echeverry, L. Lafon, A. Morquio, and H. Heizen Cell culture protection and in vivo neuroprotective capacity of flavonoids Neurotox. Res. 5 2003 425 432
30. F. Dajas, F. Rivera-Megret, F. Blasina, F. Arredondo, J.A. Abin-Carriquiry, G. Costa, C. Echeverry, L. Lafon, H. Heizen, M. Ferreira, and A. Morquio Neuroprotection by flavonoids Braz. Biol. Res. 36 2003 1613 1620
31. J.M. Davis, E.A. Murphy, M.D. Carmichael, and B. Davis Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance Am. J. Physiol. Regul. Integr. Comp. Physiol. 296 2009 R1071 R1077
32. A.J. Day, F.J. Cañada, J.C. Díaz, P.A. Kroon, R. Mclauchlan, C.B. Faulds, G.W. Plumb, M.R. Morgan, and G. Williamson Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase FEBS Lett. 468 2000 166 170
33. A.J. Day, M.S. DuPont, S. Ridley, M. Rhodes, M.J. Rhodes, M.R. Morgan, and G. Williamson Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity FEBS Lett. 436 1998 71 75
34. A.J. Day, J.M. Gee, M.S. DuPont, I.T. Johnson, and G. Williamson Absorption of quercetin-3-glucoside and quercetin-4′-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter Biochem. Pharmacol. 65 2003 1199 1206
35. A.J. Day, F. Mellon, D. Barron, G. Sarrazin, M.R. Morgan, and G. Williamson Human metabolism of dietary flavonoids: identification of plasma metabolites of quercetin Free Radic. Res. 35 2001 941 952
36. V.C.J. De Boer, A.A. Dihal, H. van der Woude, I.C.W. Arts, S. Wolffram, G.M. Alink, I.M.C.M. Rietjens, J. Keijer, and P.C.H. Hollman Tissue distribution of quercetin in rats and pigs J. Nutr. 135 2005 1718 1725
37. L.M.L. De Lau, and M.M.B. Breteler Epidemiology of Parkinson's disease Lancet. Neurol. 5 2006 525 535
38. U. De Marchi, L. Biasutto, S. Garbisa, A. Toninello, and M. Zoratti Quercetin can act either as an inhibitor or an inducer of the mitochondrial permeability transition pore: a demonstration of the ambivalent redox character of polyphenols Biochim. Biophys. Acta 1787 2009 1425 1432
39. K.M Denny Joseph, and Muralidhara Combined oral supplementation of fish oil and quercetin enhances neuroprotection in a chronic rotenone rat model: relevance to Parkinson's disease Neurochem. Res. 40 5 2015 894 905
40. C. Desmarchelier, J. Coussio, and G. Ciccia Antioxidant and free radical scavenging effects in extracts of the medicinal herb Achyrocline satureioides (Lam.) DC. ("marcela") Braz. J. Med. Biol. Res. 31 1998 1163 1170
41. E.E. Devore, J.H. Kang, M.J. Stampfer, and F. Grodstein The association of antioxidants and cognition in the Nurses' Health Study Am. J. Epidemiol. 177 2013 33 41
42. A. Dietrich-Muszalska, and B. Olas Inhibitory effects of polyphenol compounds on lipid peroxidation caused by antipsychotics (haloperidol and amisulpride) in human plasma in vitro World J. Biol. Psychiatry 11 2010 276 281
43. R. Dringen Glutathione metabolism and oxidative stress in neurodegeneration Eur. J. Biochem. 267 2000 4903
44. C. Echeverry, F. Arredondo, J.A. Abin-Carriquiry, J.O. Midiwo, C. Ochieng, L. Kerubo, and F. Dajas Pretreatment with natural flavones and neuronal cell survival after oxidative stress: a structure-activity relationship study J. Agric. Food Chem. 58 2010 2111 2115
45. C. Echeverry, F. Arredondo, M. Martínez, J.A. Abin-Carriquiry, J. Midiwo, and F. Dajas Antioxidant activity, cellular bioavailability, and iron and calcium management of neuroprotective and nonneuroprotective flavones Neurotox. Res. 27 2015 31 42
46. Emmert, D.H., Kirchner, J.T. The role of vitamin E in the prevention of heart disease. Arch. Fam. Med. 8, 537-542.
47. V. Farzaneh, and I.S. Carvalho A review of the health benefit potentials of herbal plant infusions and their mechanism of actions Ind. Crops Prod. 65 2015 247 258
48. G. La Fata, P. Weber, and M.H. Mohajeri Effects of vitamin E on cognitive performance during ageing and in Alzheimer's disease Nutrients 6 2014 5453 5472
49. J.V. Formica, and W. Regelson Review of the biology of quercetin and related bioflavonoids Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc. 33 1995 1061 1080
50. M. Fiorani, A. Guidarelli, M. Blasa, C. Azzolini, M. Candiracci, E. Piatti, and O. Cantoni Mitochondria accumulate large amounts of quercetin: prevention of mitochondrial damage and release upon oxidation of the extramitochondrial fraction of the flavonoid J. Nutr. Biochem. 21 2010 397 404
51. S. Gandhi, and A.Y. Abramov Mechanism of oxidative stress in neurodegeneration Oxid. Med. Cell. Longev. 2012 2012 428010
52. M. Gerlach, D. Ben-Shachar, P. Riederer, and M.B. Youdim Altered brain metabolism of iron as a cause of neurodegenerative diseases? J. Neurochem. 63 1994 793 807
53. E.U. Graefe, J. Wittig, S. Mueller, A.K. Riethling, B. Uehleke, B. Drewelow, H. Pforte, G. Jacobasch, H. Derendorf, and M. Veit Pharmacokinetics and bioavailability of quercetin glycosides in humans J. Clin. Pharmacol. 41 2001 492 499
54. A. Gustavsson, M. Svensson, F. Jacobi, C. Allgulander, J. Alonso, E. Beghi, R. Dodel, M. Ekman, C. Faravelli, L. Fratiglioni, B. Gannon, D.H. Jones, P. Jennum, A. Jordanova, L. Jönsson, K. Karampampa, M. Knapp, G. Kobelt, T. Kurth, R. Lieb, M. Linde, C. Ljungcrantz, A. Maercker, B. Melin, M. Moscarelli, A. Musayev, F. Norwood, M. Preisig, M. Pugliatti, J. Rehm, L. Salvador-Carulla, B. Schlehofer, R. Simon, H.-C. Steinhausen, L.J. Stovner, J.-M. Vallat, P. Van den Bergh, J. van Os, P. Vos, W. Xu, H.-U. Wittchen, B. Jönsson, and J. Olesen Cost of disorders of the brain in Europe 2010 Eur. Neuropsychopharmacol. 21 2011 718 779 10.1016/j.euroneuro.2011.08.008
55. N. Haleagrahara, C.J. Siew, and K. Ponnusamy Effect of quercetin and desferrioxamine on 6-hydroxydopamine (6-OHDA) induced neurotoxicity in striatum of rats J. Toxicol. Sci. 38 2013 25 33
56. B. Halliwell Free radicals and antioxidants: updating a personal view Nutr. Rev. 70 2012 257 265
57. B. Halliwell, and J.M.C. Gutteridge Free Radicals in Biology and Medicine, Free Radical Biology and Medicine 1999 Oxford University Press
58. Y. Hanasaki, S. Ogawa, and S. Fukui The correlation between active oxygens scavenging and antioxidative effects of flavonoids Free Radic. Biol. Med. 16 1994 845 850
59. Y. Hassaan, H. Handoussa, A.H. El-Khatib, M.W. Linscheid, N. El Sayed, and N. Ayoub Evaluation of plant phenolic metabolites as a source of Alzheimer's drug leads Biomed. Res. Int. 2014 2014 843263
60. K.E. Heim, A.R. Tagliaferro, and D.J. Bobilya Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships J. Nutr. Biochem. 13 2002 572 584
61. M.G. Hertog, P.C. Hollman, M.B. Katan, and D. Kromhout Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands Nutr. Cancer 20 1993 21 29
62. L. Ho, M.G. Ferruzzi, E.M. Janle, J. Wang, B. Gong, T.-Y. Chen, J. Lobo, B. Cooper, Q.L. Wu, S.T. Talcott, S.S. Percival, J.E. Simon, and G.M. Pasinetti Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease FASEB J. 27 2013 769 781
63. P.C. Hollman, M.G. Hertog, and M.B. Katan Role of dietary flavonoids in protection against cancer and coronary heart disease Biochem. Soc. Trans. 24 1996 785 789
64. P.C. Hollman, and M.B. Katan Absorption, metabolism and health effects of dietary flavonoids in man Biomed. Pharmacother. 51 1997 305 310
65. P.C. Hollman, L.B. Tijburg, and C.S. Yang Bioavailability of flavonoids from tea Crit. Rev. Food Sci. Nutr. 37 1997 719 738
66. K.T. Howitz, K.J. Bitterman, H.Y. Cohen, D.W. Lamming, S. Lavu, J.G. Wood, R.E. Zipkin, P. Chung, A. Kisielewski, L.-L. Zhang, B. Scherer, and D.A. Sinclair Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan Nature 425 2003 191 196
67. P. Huebbe, A.E. Wagner, C. Boesch-Saadatmandi, F. Sellmer, S. Wolffram, and G. Rimbach Effect of dietary quercetin on brain quercetin levels and the expression of antioxidant and Alzheimer's disease relevant genes in mice Pharmacol. Res. 61 2010 242 246
68. K. Ioku, Y. Pongpiriyadacha, Y. Konishi, Y. Takei, N. Nakatani, and J. Terao beta-Glucosidase activity in the rat small intestine toward quercetin monoglucosides Biosci. Biotechnol. Biochem. 62 1998 1428 1431
69. Y. Ishikawa, and M. Kitamura Anti-apoptotic effect of quercetin: intervention in the JNK- and ERK-mediated apoptotic pathways Kidney Int. 58 2000 1078 1087
70. A. Ishisaka, S. Ichikawa, H. Sakakibara, M.K. Piskula, T. Nakamura, Y. Kato, M. Ito, K. Miyamoto, A. Tsuji, Y. Kawai, and J. Terao Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats Free Radic. Biol. Med. 51 2011 1329 1336
71. A. Ishisaka, R. Mukai, J. Terao, N. Shibata, and Y. Kawai Specific localization of quercetin-3-O-glucuronide in human brain Arch. Biochem. Biophys. 557 2014 11 17
72. I.B. Jaganath, W. Mullen, C.A. Edwards, and A. Crozier The relative contribution of the small and large intestine to the absorption and metabolism of rutin in man Free Radic. Res. 40 2006 1035 1046
73. I.B. Jaganath, W. Mullen, M.E.J. Lean, C.A. Edwards, and A. Crozier In vitro catabolism of rutin by human fecal bacteria and the antioxidant capacity of its catabolites Free Radic. Biol. Med. 47 2009 1180 1189
74. A. Kakizuka Protein precipitation: a common etiology in neurodegenerative disorders? Trends Genet. 14 1998 396 402
75. C.-H. Kang, Y.H. Choi, S.-K. Moon, W.-J. Kim, and G.-Y. Kim Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-dependent HO-1 pathway Int. Immunopharmacol. 17 2013 808 813
76. S.S. Karuppagounder, S.K. Madathil, M. Pandey, R. Haobam, U. Rajamma, and K.P. Mohanakumar Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson's disease in rats Neuroscience 236 2013 136 148
77. K. Kawabata, Y. Kawai, and J. Terao Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats J. Nutr. Biochem. 21 2010 374 380
78. H. Kinouchi, C.J. Epstein, T. Mizui, E. Carlson, S.F. Chen, and P.H. Chan Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase Proc. Natl. Acad. Sci. U. S. A. 88 1991 11158 11162
79. H. Kobuchi, S. Roy, C.K. Sen, H.G. Nguyen, and L. Packer Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway Am. J. Physiol. 277 1999 C403 C411
80. J. Kressler, M. Millard-Stafford, and G.L. Warren Quercetin and endurance exercise capacity: a systematic review and meta-analysis Med. Sci. Sports Exerc. 43 2011 2396 2404
81. J. Kühnau The flavonoids. A class of semi-essential food components: their role in human nutrition World Rev. Nutr. Diet. 24 1976 117 191
82. A. Kumar, N. Sehgal, P. Kumar, S.S.V. Padi, and P.S. Naidu Protective effect of quercetin against ICV colchicine-induced cognitive dysfunctions and oxidative damage in rats Phytother. Res. 22 2008 1563 1569
83. R. Lagoa, I. Graziani, C. Lopez-Sanchez, V. Garcia-Martinez, and C. Gutierrez-Merino Complex I and cytochrome c are molecular targets of flavonoids that inhibit hydrogen peroxide production by mitochondria Biochim. Biophys. Acta 1807 2011 1562 1572
84. J.D. Lambert, S. Sang, and C.S. Yang Possible controversy over dietary polyphenols: benefits vs risks Chem. Res. Toxicol. 20 2007 583 585
85. D.J. Lamport, C. Saunders, L.T. Butler, and J.P. Spencer Fruits, vegetables, 100% juices, and cognitive function Nutr. Rev. 72 2014 774 789
86. A.J. Larson, J.D. Symons, and T. Jalili Quercetin: a treatment for hypertension? - a review of Efficacy and mechanisms Pharmaceuticals 3 2010 237 250
87. S. Lavoie, Y. Chen, T.P. Dalton, R. Gysin, M. Cuénod, P. Steullet, and K.Q. Do Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit J. Neurochem. 108 2009 1410 1422
88. Y.Y. Lee-Hilz, A.-M.J.F. Boerboom, A.H. Westphal, W.J.H. Berkel, J.M.M.J.G. van Aarts, and I.M.C.M. Rietjens Pro-oxidant activity of flavonoids induces EpRE-mediated gene expression Chem. Res. Toxicol 19 2006 1499 1505
89. Y. Li, S. Zhou, J. Li, Y. Sun, H. Hasimu, R. Liu, and T. Zhang Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1-40-induced toxicity Acta Pharm. Sin. B 5 2015 47 54
90. J.J. Liu, D.J. Casley, and W.G. Nayler Ischaemia causes externalization of endothelin-1 binding sites in rat cardiac membranes Biochem. Biophys. Res. Commun. 164 1989 1220 1225
91. C. Lu, Y. Lu, J. Chen, W. Zhang, and W. Wu Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system Eur. J. Pharm. Biopharm. 66 2007 210 219
92. C. Lv, T. Hong, Z. Yang, Y. Zhang, L. Wang, M. Dong, J. Zhao, J. Mu, and Y. Meng Effect of quercetin in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced mouse model of Parkinson's disease Evid. Based. Complement. Altern. Med. 2012 2012 928643
93. K.B. Magalingam, A. Radhakrishnan, and N. Haleagrahara Protective effects of flavonol isoquercitrin, against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells BMC Res. Notes 7 2014 49
94. K.B. Magalingam, A. Radhakrishnan, P. Ramdas, and N. Haleagrahara Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson's disease J. Mol. Neurosci. 55 2015 609 617
95. C. Manach, G. Williamson, C. Morand, A. Scalbert, and C. Rémésy Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies Am. J. Clin. Nutr. 81 2005 230S 242S
96. S.A. Mandel, Y. Avramovich-Tirosh, L. Reznichenko, H. Zheng, O. Weinreb, T. Amit, and M.B.H. Youdim Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway Neurosignals 14 2005 46 60
97. C.J. Maxwell, M.S. Hicks, D.B. Hogan, J. Basran, and E.M. Ebly Supplemental use of antioxidant vitamins and subsequent risk of cognitive decline and dementia Dement. Geriatr. Cogn. Disord. 20 2005 45 51
98. P. Mecocci, C. Tinarelli, R.J. Schulz, and M.C. Polidori Nutraceuticals in cognitive impairment and Alzheimer's disease Front. Pharmacol. 5 2014 147
99. E.E. Mendoza, and R. Burd Quercetin as a systemic chemopreventative agent: structural and functional mechanisms Mini Rev. Med. Chem. 11 2011 1216 1221
100. D. Metodiewa, A.K. Jaiswal, N. Cenas, E. Dickancaité, and J. Segura-Aguilar Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product Free Radic. Biol. Med. 26 1999 107 116
101. E.J. Middleton Effect of plant flavonoids on immune and inflammatory cell function Adv. Exp. Med. Biol. 439 1998 175 182
102. N.J. Miller, and M.B. Ruiz-Larrea Flavonoids and other plant phenols in the diet: their significance as antioxidants J. Nutr. Environ. Med. 12 2002 39 51
103. L. Mira, M.T. Fernandez, M. Santos, R. Rocha, M.H. Florêncio, and K.R. Jennings Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity Free Radic. Res. 36 2002 1199 1208
104. S.-K. Moon, G.-O. Cho, S.-Y. Jung, S.-W. Gal, T.K. Kwon, Y.-C. Lee, N.R. Madamanchi, and C.-H. Kim Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: role of ERK1/2, cell-cycle regulation, and matrix metalloproteinase-9 Biochem. Biophys. Res. Commun. 301 2003 1069 1078
105. C. Morand, V. Crespy, C. Manach, C. Besson, C. Demigné, and C. Rémésy Plasma metabolites of quercetin and their antioxidant properties Am. J. Physiol. 275 1998 R212 R219
106. K. Muraoka, K. Shimizu, X. Sun, T. Tani, R. Izumi, K. Miwa, and K. Yamamoto Flavonoids exert diverse inhibitory effects on the activation of NF-kappaB Transpl. Proc. 34 2002 1335 1340
107. K. Murota, A. Hotta, H. Ido, Y. Kawai, J.-H. Moon, K. Sekido, H. Hayashi, T. Inakuma, and J. Terao Antioxidant capacity of albumin-bound quercetin metabolites after onion consumption in humans J. Med. Investig. 54 2007 370 374
108. M.C.W. Myhrstad, H. Carlsen, O. Nordström, R. Blomhoff, and J.∅. Moskaug Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter Free Radic. Biol. Med. 32 2002 386 393
109. P.S. Naidu, and S.K. Kulkarni Quercetin, a bioflavonoid, reverses haloperidol-induced catalepsy Methods Find. Exp. Clin. Pharmacol. 26 2004 323 326
110. M. Nassiri-Asl, S. Moghbelinejad, E. Abbasi, F. Yonesi, M.-R. Haghighi, M. Lotfizadeh, and P. Bazahang Effects of quercetin on oxidative stress and memory retrieval in kindled rats Epilepsy Behav. 28 2013 151 155
111. K. Németh, G.W. Plumb, J.-G. Berrin, N. Juge, R. Jacob, H.Y. Naim, G. Williamson, D.M. Swallow, and P.A. Kroon Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans Eur. J. Nutr. 42 2003 29 42
112. R.J. Nijveldt, E. van Nood, D.E. van Hoorn, P.G. Boelens, K. van Norren, and P.A. van Leeuwen Flavonoids: a review of probable mechanisms of action and potential applications Am. J. Clin. Nutr. 74 2001 418 425
113. A.C.J. Nooyens, H.B. Bueno-de-Mesquita, M.P.J. van Boxtel, B.M. van Gelder, H. Verhagen, and W.M.M. Verschuren Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study Br. J. Nutr. 106 2011 752 761
114. G. Notas, A.-P. Nifli, M. Kampa, V. Pelekanou, V.-I. Alexaki, P. Theodoropoulos, J. Vercauteren, and E. Castanas Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells J. Nutr. Biochem. 23 2012 656 666
115. K. Ohta, A. Mizuno, S. Li, M. Itoh, M. Ueda, E. Ohta, Y. Hida, M. Wang, M. Furoi, Y. Tsuzuki, M. Sobajima, Y. Bohmoto, T. Fukushima, M. Kobori, T. Inuzuka, and T. Nakagawa Endoplasmic reticulum stress enhances γ-secretase activity Biochem. Biophys. Res. Commun. 416 2011 362 366
116. C.W. Olanow, and W.G. Tatton Etiology and pathogenesis of Parkinson's disease Annu. Rev. Neurosci. 22 1999 123 144
117. M.R. Olthof, P.C. Hollman, T.B. Vree, and M.B. Katan Bioavailabilities of quercetin-3-glucoside and quercetin-4′-glucoside do not differ in humans J. Nutr. 130 2000 1200 1203
118. K. Ono, Y. Yoshiike, A. Takashima, K. Hasegawa, H. Naiki, and M. Yamada Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease J. Neurochem. 87 2003 172 181
119. B. Ossola, T.M. Kääräinen, A. Raasmaja, and P.T. Männistö Time-dependent protective and harmful effects of quercetin on 6-OHDA-induced toxicity in neuronal SH-SY5Y cells Toxicology 250 2008 1 8
120. B. Ossola, T.M. Kääriäinen, and P.T. Männistö The multiple faces of quercetin in neuroprotection Expert Opin. Drug Saf. 8 2009 397 409
121. F. Perez-Vizcaino, J. Duarte, and C. Santos-Buelga The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids J. Sci. Food Agric. 92 2012 1822 1825
122. H. Pforte, J. Hempel, and G. Jacobasch Distribution pattern of a flavonoid extract in the gastrointestinal lumen and wall of rats Nahrung 43 1999 205 208
123. G. Reiterer, M. Toborek, and B. Hennig Quercetin protects against linoleic acid-induced porcine endothelial cell dysfunction J. Nutr. 134 2004 771 775
124. C. Reitz, C. Brayne, and R. Mayeux Epidemiology of Alzheimer disease Nat. Rev. Neurol. 7 2011 137 152
125. D. Retta, E. Dellacassa, J. Villamil, S.A. Suárez, and A.L. Bandoni Marcela, a promising medicinal and aromatic plant from Latin America: a review Ind. Crops Prod. 38 2012 27 38
126. C. Rice-Evans Flavonoid antioxidants Curr. Med. Chem. 8 2001 797 807
127. F. Rivera, J. Urbanavicius, E. Gervaz, A. Morquio, and F. Dajas Some aspects of the in vivo neuroprotective capacity of flavonoids: bioavailability and structure-activity relationship Neurotox. Res. 6 2004 543 553
128. F. Rivera Megret, D. Tejera Correa, JA. Abin Carriquiri, G. Prunell dos Santos, M. Martínez Busi, and F. Dajas Achyrocline satureioides (Lam.) DC. (marcela) reduces brain damage in permanent focal ischemia in rats Rev. Cubana Plantas Med. 18 3 2013 445 460
129. M. Russo, C. Spagnuolo, I. Tedesco, S. Bilotto, and G.L. Russo The flavonoid quercetin in disease prevention and therapy: facts and fancies Biochem. Pharmacol. 83 2012 6 15
130. A.M. Sabogal-Guáqueta, J.I. Muñoz-Manco, J.R. Ramírez-Pineda, M. Lamprea-Rodriguez, E. Osorio, and G.P. Cardona-Gómez The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice Neuropharmacology 93C 2015 134 145
131. R. Sandhir, and A. Mehrotra Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid: implications in Huntington's disease Biochim. Biophys. Acta 1832 2013 421 430
132. A.L.A. Sesink, I.C.W. Arts, M. Faassen-Peters, and P.C.H. Hollman Intestinal uptake of quercetin-3-glucoside in rats involves hydrolysis by lactase phlorizin hydrolase J. Nutr. 133 2003 773 776
133. A.Y. Shih, D.A. Johnson, G. Wong, A.D. Kraft, L. Jiang, H. Erb, J.A. Johnson, and T.H. Murphy Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress J. Neurosci. 23 2003 3394 3406
134. K. Shimoi, H. Okada, M. Furugori, T. Goda, S. Takase, M. Suzuki, Y. Hara, H. Yamamoto, and N. Kinae Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans FEBS Lett. 438 1998 220 224
135. N.A. Simonian, and J.T. Coyle Oxidative stress in neurodegenerative diseases Annu. Rev. Pharmacol. Toxicol. 36 1996 83 106
136. J.P.E. Spencer The interactions of flavonoids within neuronal signalling pathways Genes. Nutr. 2 2007 257 273
137. J.P.E. Spencer, C. Rice-Evans, and R.J. Williams Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability J. Biol. Chem. 278 2003 34783 34793
138. N. Sriraksa, J. Wattanathorn, S. Muchimapura, S. Tiamkao, K. Brown, and K. Chaisiwamongkol Cognitive-enhancing effect of quercetin in a rat model of Parkinson's disease induced by 6-hydroxydopamine Evid. Based. Complement. Altern. Med. 2012 2012 823206
139. K. Takashima, M. Matsushima, K. Hashimoto, H. Nose, M. Sato, N. Hashimoto, Y. Hasegawa, and T. Kawabe Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury Respir. Res. 15 2014 150
140. J. Terao, K. Murota, and Y. Kawai Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo Food Funct. 2 2011 11 17
141. B.J. Thompson, and P.T. Ronaldson Drug delivery to the ischemic brain Adv. Pharmacol. 71 2014 165 202
142. B. Uttara, A.V. Singh, P. Zamboni, and R.T. Mahajan Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options Curr. Neuropharmacol. 7 2009 65 74
143. D. Vauzour, K. Vafeiadou, A. Rodriguez-Mateos, C. Rendeiro, and J.P.E. Spencer The neuroprotective potential of flavonoids: a multiplicity of effects Genes. Nutr. 3 2008 115 126
144. H. Vaziri, S.K. Dessain, E. Ng Eaton, S.I. Imai, R.A. Frye, T.K. Pandita, L. Guarente, and R.A. Weinberg hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase Cell 107 2001 149 159
145. R.A. Walgren, K.J. Karnaky, G.E. Lindenmayer, and T. Walle Efflux of dietary flavonoid quercetin 4′-beta-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance-associated protein-2 J. Pharmacol. Exp. Ther. 294 2000 830 836
146. R.A. Walgren, J.T. Lin, R.K. Kinne, and T. Walle Cellular uptake of dietary flavonoid quercetin 4′-beta-glucoside by sodium-dependent glucose transporter SGLT1 J. Pharmacol. Exp. Ther. 294 2000 837 843
147. T. Walle Methylation of dietary flavones increases their metabolic stability and chemopreventive effects Int. J. Mol. Sci. 10 2009 5002 5019
148. J.M. Williams, A.M. Beckmann, S.E. Mason-Parker, W.C. Abraham, P.A. Wilce, and W.P. Tate Sequential increase in Egr-1 and AP-1 DNA binding activity in the dentate gyrus following the induction of long-term potentiation. Brain Res Mol. Brain Res. 77 2000 258 266
149. R.J. Williams, J.P.E. Spencer, and C. Rice-Evans Flavonoids: antioxidants or signalling molecules? Free Radic. Biol. Med. 36 2004 838 849
150. W.J. Wilson, and L. Poellinger The dietary flavonoid quercetin modulates HIF-1 alpha activity in endothelial cells Biochem. Biophys. Res. Commun. 293 2002 446 450
151. C. Xu, B. Bailly-Maitre, and J.C. Reed Endoplasmic reticulum stress: cell life and death decisions J. Clin. Investig. 115 2005 2656 2664
152. Yoshino, S., Hara, A., Sakakibara, H., Kawabata, K., Tokumura, A., Ishisaka, A., Kawai, Y., Terao, J. Effect of quercetin and glucuronide metabolites on the monoamine oxidase-A reaction in mouse brain mitochondria. Nutrition 27, 847-852.
153. V. Zbarsky, K.P. Datla, S. Parkar, D.K. Rai, O.I. Aruoma, and D.T. Dexter 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. 39 2005 1119 1125
154. F. Zemek, L. Drtinova, E. Nepovimova, V. Sepsova, J. Korabecny, J. Klimes, and K. Kuca Outcomes of Alzheimer's disease therapy with acetylcholinesterase inhibitors and memantine Expert Opin. Drug Saf. 13 2014 759 774
155. J. Zhang, R.A. Stanley, A. Adaim, L.D. Melton, and M.A. Skinner Free radical scavenging and cytoprotective activities of phenolic antioxidants Mol. Nutr. Food Res. 50 2006 996 1005
156. X.D. Zhang, X.Q. Liu, Y.H. Kim, and W.K. Whang Chemical constituents and their acetyl cholinesterase inhibitory and antioxidant activities from leaves of Acanthopanax henryi: potential complementary source against Alzheimer's disease Arch. Pharm. Res. 37 2014 606 616
157. L. Zhao, J.-L. Wang, Y.-R. Wang, and X.-Z. Fa Apigenin attenuates copper-mediated β-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model Brain Res. 1492 2012 33 45