Life or death: Neuroprotective and anticancer effects of quercetin

Journal of Ethnopharmacology

Volumn 143, Issue 2, 2012, Pages 383-396

  Dajas, Federico ^a  

^a INSTITUTO DE INVESTIGACIONES BIOLÓGICAS CLEMENTE ESTABLE   (Uruguay)

Author keywords

Anticancer; Neuroprotection; Oxidative stress; Quercetin; Signaling

Indexed keywords

APOPTOTIC PROTEASE ACTIVATING FACTOR 1; CASPASE 8; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; CYTOCHROME C; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN BAX; PROTEIN KINASE B; QUERCETIN; RAF PROTEIN; RAS PROTEIN; SUPEROXIDE DISMUTASE; TUMOR NECROSIS FACTOR ALPHA;

ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; BRAIN; CELL DEATH; CELL SURVIVAL; COGNITIVE DEFECT; COLON CARCINOGENESIS; COLORECTAL CANCER; DNA DAMAGE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; ENZYME ACTIVITY; GENE EXPRESSION; GLIOMA; HELA CELL; HIPPOCAMPUS; HUMAN; IN VIVO STUDY; LIPID PEROXIDATION; MELANOMA; NERVE CELL GROWTH; NEUROPROTECTION; NONHUMAN; OSTEOSARCOMA; OXIDATIVE STRESS; PROSTATE CANCER; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; BIOLOGICAL AVAILABILITY; HUMANS; NEUROPROTECTIVE AGENTS; QUERCETIN;

EID: 84866045756     PISSN: 03788741     EISSN: 18727573     Source Type: Journal    
DOI: 10.1016/j.jep.2012.07.005     Document Type: Review

References (144)

1. A. Acharya, I. Das, D. Chandhok, and T. Saha Redox regulation in cancer. A double-edged sword with therapeutic potential Oxidative Medicine and Cellular Longevity 3 2010 23 34
2. G. Agullo, L. Gamet Payastre, S. Maneneti, C. Viala, C. Remesy, H. Chap, and B. Payrastre Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition Biochemical Pharmacology 53 1997 1649 1657
3. M.A. Ansari, H.M. Abdul, G. Joshi, W.O. Opii, and A. Butterfield Protective effect of quercetin in primary neurons against a β (1-42): relevance to Alzheimer's disease Journal of Nutritional Biochemistry 20 2009 269 275
4. F. Arredondo, C. Echeverry, J. Abin-Carriquiry, F. Blasina, K. Antúnez, D. Jones, Y. Go, 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 Radical Biology and Medicine 49 2010 738 747
5. A. Bach, J. Bender-Sigel, D. Schrenk, D. Flügel, and T. Kietzmann The antioxidant quercetin inhibits cellular proliferation via HIF-1-dependent induction of p21WAF Antioxidant and Redox Signaling 13 2010 437 448
6. C.P. Baines, R.A. Kaiser, N.H. Purcell, N.S. Blair, H. Osinska, M.A. Hambleton, E.W. Brunskill, M.R. Sayen, R.A. Gottlieb, G.W. Dorn, J. Robbins, and J.D. Molkentin Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death Nature 434 2005 658 662
7. O. Benavente-García, and J. Castillo Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity Journal of Agricultural and Food Chemistry 56 2008 6185 6205
8. S.C. Benn, and C.J. Woolf Adult neuron survival strategies - slamming on the brakes Nature Reviews Neuroscience 5 2004 686 700
9. M. Bergeron, J.M. Gidday, S.A. Yu, Y. Semenza, G.L. Ferriero, and D.M. Sharp, F.R. Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain Annals of Neurology 48 2000 285 296
10. J. Bieger, R. Cermak, R. Blank, V.C. de Boer, P.C. Hollman, J. Kamphues, and S. Wolffram Tissue distribution of quercetin in pigs after long-term dietary supplementation Journal of Nutrition 138 2008 1417 1420
11. A. Bindoli, M. Valente, and L. Cavallin Inhibitory action of quercetin on xanthine oxidase and xanthine dehydrogenase activity Pharmacological Research Communications 17 1985 831 839
12. S.C. Bischoff Quercetin: potentials in the prevention and therapy of disease Current Opinion in Clinical Nutrition and Metabolic Care 11 2008 733 740
13. F. Blasina, L. Vaamonde, A. Morquio, C. Echeverry, F. Arredondo, and F. Dajas Differentiation induced by Achyrocline satureioides (Lam) infusion in PC12 cells Phytotherapy Research 23 2009 1263 1269
14. A.W. Boots, G. Haenen, G. Hartog, and A. Bast Oxidative damage shifts from lipid peroxidation to thiol arylation by catechol-containing antioxidants Biochemical Biophysical Acta 1583 2002 279 284
15. A.W. Boots, G.R. Haenen, and A. Bast Health effects of quercetin: from antioxidant to nutraceutical European Journal of Pharmacology 585 2008 325 337
16. E. Braganhol, L.L. Zamin, A.D. Canedo, F. Horn, A.S. Tamajusuku, M.R. Wink, C. Salbego, and A.M. Battastini Antiproliferative effect of quercetin in the human U138MG glioma cell line Anticancer Drugs 17 2006 663 671
17. A. Brunet, S.R. Datta, and M.E. Greenberg Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway Current opinion in Neurobiology 11 2001 297 305
18. G. Bureau, F. Longpré, and M.G. Martinoli Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation Journal of Neuroscience Research 86 2008 403 410
19. Y. Caia, Q. Luob, M. Sunc, and H. Corke Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer Life Sciences 74 2004 2157 2184
20. S.K. Calderwood, M.A. Khaleque, D.B. Sawyer, and D.R. Ciocca Heat shock proteins in cancer: chaperones of tumorigenesis Trends in Biochemical Sciences 31 2006 164 172
21. S. Caltagirone, C. Rossi, A. Poggi, F.O. Ranelletti, P.G. Natali, M. Brunetti, F.B. Aiello, and M. Piantelli Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential International Journal of Cancer 87 2000 595 600
22. C. Carrasco-Pozo, M. Mizgier, L. Speisky, and H. Gotteland, M. Differential protective effects of quercetin, resveratrol, rutin and epigallocatechin gallate against mitochondrial dysfunction induced by indomethacin in Caco-2 cells Chemical Biological Interactions 195 2012 199 205
23. C. Chen, J. Zhou, and C. Ji Quercetin: a potential drug to reverse multidrug resistance Life Sciences 87 2010 333 338
24. J.C. Chen, F.M. Ho, C. Pei-Dawn Lee, C.P. Chen, K.C. Jeng, H.B. Hsu, S.T. Lee, W.T. Wu, 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 European Journal of Pharmacology 521 2005 9 20
25. E. Choi, S.M. Bae, and W.S. Ahn Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB- 453 cells Archives of Pharmacal Research 31 2008 1281 1285
26. D.R. Ciocca, and S.K. Calderwood Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications Cell Stress and Chaperones 10 2005 86 103
27. S. Cory, and J.M. Adams The BCL family: regulators of the cellular life-or-death- switch Cancer Nature Reviews 2 2002 647 656
28. V. Crespy, C. Morand, C. Besson, C. Manach, C. Démigné, and C. Rémésy Comparison of the intestinal absorption of quercetin, phloretin and their glucosides in rats Journal of Nutrition 13 2001 2109 2114
29. F. Dajas, F. Arredondo, C. Echeverry, M. Ferreira, A. Morquio, and F. Rivera Flavonoids and the brain: evidences and putative mechanisms for a protective capacity 3 2005 193 205 Current Neuropharmacology 3 2005 193 205
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 Brazilian Journal of Medical and Biological Research 36 2003 1613 1620
31. 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 flavonoid Neurotoxicity Research 5 2003 377 384
32. V.C.J. De Boer, A.A. Dihal, H. van der Woude, I.C.W. Arts, S. Wolffram, G.M. Alink, K.J. Rietjens, and P.C.H. Hollman Tissue distribution of quercetin in rats and pigs Journal of Nutrition 135 2005 1718 1725
33. 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 Biochimica et Biophisica Acta 1787 2009 1425 1432
34. G.J. Del Zoppo, F.R. Sharp, W.D. Heiss, and G.W. Albers Heterogeneity in the penumbra Journal of Cerebral Blood Flow and Metabolism 31 2011 1836 1851
35. M. Dhanasekaran, L.A. Holcomb, A.R. Hitt, B. Tharakan, J.W. Porter, K.A. Young, and B.V. Manyam Centella asiatica extract selectively decreases amyloid beta levels in hippocampus of Alzheimer's disease animal model Phytotherapy Research 23 2009 14 19
36. G. Du, H. Lin, M. Wang, S. Zhang, X. Wu, L. Lu, L. Ji, and L. Yu Quercetin greatly improved therapeutic index of doxorubicin against 4T1 breast cancer by its opposing effects on HIF-1α in tumor and normal cells Cancer Chemotherapy and Pharmacology 65 2010 277 287
37. J. Duraj, K. Zazrivcova, J. Bodo, M. Sulikova, and J. Sedlak Flavonoid quercetin, but not apigenin or luteolin, induced apoptosis in human myeloid leukemia cells and their resistant variants Neoplasma 52 2005 273 279
38. Echeverry, C.; Arredondo, F.; Abin-Carriquiry, J.A.; Midiwo, J.O.; Ochieng, 2010
39. S. Egert, S. Wolffram, A. Bosy-Westphal, C. Boesch-Saadatmandi, E.A. Wagner, J. Frank, G. Rimbach, and M. Mueller Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans Journal of Nutrition 138 2008 1615 1621
40. I.V. Ekimova, T.G. Komarova, L.E. Nitsinskaya, Yu.F. Pastukhov, and I.V. Guzhova Effects of exogenous heat shock protein 70 and quercetin on NMDA-induced seizures Doklady Biological Sciences 418 2008 13 15
41. S. Elchuri, T.D. Oberley, W. Qi, R.S. Eisenstein, R.L. Jackson, H. Van Remmen, C.J. Epstein, and T.T. Huang CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life Oncogene 24 2005 367 380
42. J. Emerit, M. Edeas, and F. Bricaire Neurodegenerative diseases and oxidative stress Biomedicine and Pharmacotherapy 58 2004 39 46
43. A. Faria, D. Pestana, D. Teixeira, J. Azevedo, V. De Freitas, N. Mateus, and C. Calhau Flavonoid transport across RBE4 cells: a blood-brain barrier model Cellular and Molecular Biology Letters 15 2010 234 241
44. P.C. Ferriola, V. Cody, and E. Middleton Protein kinase C inhibition by plant flavonoids. Kinetic mechanisms and structure activity relationships Biochemical Pharmacology 38 1989 1617 1624
45. D.R. Ferry, A. Smith, J. Malkhandi, D.W. Fyfe, P.G. de Takats, D. Anderson, J. Baker, and D.J. Kerr Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition Clinical Cancer Research 2 1996 659 668
46. M. Fiorania, A. Guidarellib, M. Blasaa, C. Azzolinia, M. Candiraccia, E. Piattia, and H. Canton Mitochondria accumulate large amounts of quercetin: prevention of mitochondrial damage and release upon oxidation of the extramitochondrial fraction of the flavonoid The Journal of Nutritional Biochemistry 21 2010 397 404
47. J.V. Formica, and W. Regelsont Review of the biology of quercetin and related bioflavonoids Food and Chemical Toxicity 33 1995 1061 1080
48. L. Gibellini, M. Pinti, M. Nasi, S. De Biasi, R. Roat, L. Bertoncelli, and A. Cossarizza Interfering with ROS metabolism in cancer cells: the potential role of quercetin Cancer 2 2010 1288 1311
49. Gibellini, L.; Pinti, M.; Nasi, M.; Montagna, J.P.; De Biasi, S.; Roat, E.; Bertoncelli, L.; Cooper, E.L.; Cossarizza, A.; 2011. Quercetin and Cancer Chemoprevention. Evidence-based Complementary and Alternative Medicine 2011: Article ID 591356, doi:10.1093/ecam/neq053.
50. O. Gonzalez, V. Fontanes, S. Raychaudhuri, R. Loo, J. Loo, V. Arumugaswami, R. Sun, A. Dasgupta, and S.W. French The heat shock protein inhibitor quercetin attenuates hepatitis C virus production Hepatology 50 2009 1756 1764
51. Graham, M.L. Quinn, D.S. Fabricant, and N.R. Farnsworth Plants used against cancer - an extension of the work of Jonathan Hartwell Journal of Ethnopharmacology 73 2000 347 377
52. A.B. Granado-Serrano, M.A. Martin, L. Bravo, L. Goya, and S. Ramos Time-course regulation of quercetin on cell survival/proliferation pathways in human hepatoma cells Molecular Nutrition and Food Research 52 2008 457 464
53. L.A. Greene, and A.S. Tischler Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells, which respond to nerve growth factor Procceedings of the National Academy of Sciences 73 1976 2424 2428
54. A. Gross, J.M. McDonnell, and S.J. Korsmeyer BCL-2 family members and the mitochondria in apoptosis Genes and Development 13 1999 1899 1911
55. J. Guo, T. Zhu, Z. Xiao, and C. Chen Modulation of intracellular signalling pathways to induce apoptosis in prostate cancer cells Journal of Biological Chemistry 282 2007 24364 24372
56. D.G. Hardie Signal transduction: how cells sensate energy Nature 472 2011 176 177
57. S. Haupt, M. Berger, Z. Goldberg, and Y. Haupt Apoptosis - the p53 network Journal of Cell Science 116 2003 4077 4085
58. M.G. Hertog, E.J. Feskens, P.C. Hollman, M.B. Katan, and D. Kromhout Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study Lancet 342 1993 1007 1011
59. 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 Nutrition and Cancer 20 1993 21 29
60. N. Hosokawa, K. Hirayoshi, H. Kudo, H. Takechi, A. Aoike, K. Kawai, and K. Nagata Inhibition of the activation of heat shock factor in vivo and in vitro by flavonoids Molecular and Cellular Biology 12 1992 3490 3498
61. T.C. Hsieh, and J.M. Wu Targeting CWR22Rv1 prostate cancer cell proliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin Anticancer Research 29 2009 4025 4032
62. 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 Radical Biology and Medicine 51 2011 1329 1336
63. Y. Ishikawa, H. Sugiyama, E. Stylianou, and M. Kitamura Bioflavonoid quercetin inhibits interleukin-1-induced transcriptional expression of monocyte chemoattractant protein-1 in glomerular cells via suppression of nuclear factor-kappaB Journal of the American Society of Nephrology 10 1999 2290 2296
64. J. Jakubowicz-Gil, W. Rzeski, B. Zdzisinska, P. Dobrowolski, and A. Gawron Cell death and neuronal arborization upon quercetin treatment in rat neurons Acta Neurobiologiae Experimentalis 68 2008 139 146
65. J. Jakubowicz-Gil, J. Rzymowska, and A. Gawron Quercetin, apoptosis and heat shock Biochemical Pharmacology 64 2002 1591 1595
66. J.H. Jung, J.O. Lee, J.H. Kim, S.K. Lee, G.Y. You, S.H. Park, J.M. Park, E.K. Kim, P.G. Suh, J.K. An, and H.S. Kim Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation Journal of Cell Physiology 223 2010 408 414
67. A. Jyoti, and D. Sharma Neuroprotective role of Bacopa monniera extract againstaluminium-induced oxidative stress in the hippocampus of rat brain Neurotoxicology 27 2006 451 457
68. T.M. Kääriäinena, M. Piltonenb, B. Ossola, H. Kekkia, S. Lehtonena, T. Nenonenb, A. Lecklina, A. Raasmajab, and P.T. Männistöa Lack of robust protective effect of quercetin in two types of 6-hydroxydopamine- induced parkinsonian models in rats and dopaminergic cell cultures Brain Research 1203 2008 149 159
69. J.W. Kang, J.H. Kim, K. Song, S.H. Kim, J.H. Yoon, and K.S. Kim Kaempferol and quercetin, components of Ginkgo biloba extract (EGb 761), induce caspase-3-dependent apoptosis in oral cavity cancer cells Phytotherapy Research 24 2010 S77 S82
70. G.S. Kelly Quercetin Alternative Medicine Review 16 2011 172 193
71. L. Khandrika, B. Kumar, S. Koul, P. Maroni, and H.K. Koul Oxidative stress in prostate cancer Cancer Letters 282 2009 125 136
72. N.R. Kim, S.W. Park, J.G. Lee, and Y.H. Kim Protective effects of olanzapine and haloperidol on serum withdrawal-induced apoptosis in SH- SY5Y cells Progress in Neuro-psychopharmacology and Biological Psychiatry 32 2008 633 642
73. G. Klein, E. Vellenga, M.W. Fraaije, W.A. Kamps, and E.S. de Bont The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g.; acute leukemia Critical Reviews in Oncology/Hematology 50 2004 87 100
74. J. Kressler, M. Millard-Stafford, and G.L. Warren Quercetin and endurance exercise capacity: a systematic review and meta-analysis Medicine and Science in Sports and Exercise 43 2011 2396 2404
75. V. Kumar Potential medicinal plants for CNS disorders: an overview Phytotherapy Research 20 2006 1023 1035
76. A. Kumar, N. Sehgal, p. Kumar, S. Padi, and P. Naidu Protective effect of quercetin against ICV colchicine-induced cognitive dysfunctions and oxidative damage in rats Phytotherapy Research 22 2008 1563 1569
77. P.B.N. Kumar, A.P. Gupta, and B.S.K. Kaul A rapid RP-HPTLC densitometry method for simultaneous determination of major flavonoids in important medicinal plants Journal of Separation Science 30 2007 2092 2096
78. D.W. Lamson, and M.S. Brignall Antioxidants and cancer III: quercetin Alternative Medicine Review 5 2000 196 208
79. 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
80. J.K. Lee, H.J. Kwak, M.S. Piao, J.W. Jang, S.H. Kim, and H.S. Kim Quercetin reduces the elevated matrix metalloproteinases-9 level and improves functional outcome after cerebral focal ischemia in rats Acta Neurochirurgica 153 2011 1321 1329
81. Y.K. Lee, J.T. Hwang, D.Y. Kwon, Y.J. Surh, and O.J. Park Induction of apoptosis by quercetin is mediated through AMPKalpha1/ASK1/p38 pathway Cancer Letters 292 2010 228 236
82. S.G. Li, X.X. Dong, Y.J. Shan, Z. Liang, M. Xun, and L.L. Yuan Non-alkaloid components from Uncaria sinensis (Oliv.) Havil and their chemotaxonomic significance Journal of Medicinal Plants Research 5 2011 4962 4967
83. S. Lindquist, and E.A. Craig The heat shock proteins Annual Review of Genetic 22 1988 631 677
84. J. Lu, Y.L. Zheng, L. Luo, D. Wu, D. Sun, and Y. Feng Quercetin reverses d-galactose induced neurotoxicity in mouse brain Behavior Brain Research 171 2006 251 260
85. H. Lu, R.A. Forbes, and A. Verma Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis Journal of Biological Chemistry 277 2002 23111 23115
86. C. Manach, C. Morand, O. Texier, M. Favier, G. Agullo, C. Demigne, F. Regerat, and C. Remesy Quercetin metabolites in plasma of rats fed diets Journal of Nutrition 125 1995 1911 1922
87. M.L. McCullough, J.J. Peterson, R. Patel, P.F. Jacques, R. Shah, and J.T. Dwyer Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults American Journal of Clinical Nutrition 95 2012 454 464
88. E.E. Mendoza, and R. Burd Quercetin as a systemic chemopreventative agent: structural and functional mechanisms Mini-Reviews in Medicinal Chemistry 11 2011 1216 1221
89. L. Mira, M.T. Fernandez, M. Santos, R. Rocha, M.H. Florencio, and K.R Jennings Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity Free Radical Research 36 2002 1199 1208
90. A.J. Montero, and J. Jassem Cellular redox pathways as a therapeutic target in the treatment of cancer Drugs 71 2011 1385 1396
91. C. Morand, C. Manach, V. Crespy, and C. Remesy Respective bioavailability of quercetin aglycone and its glycosides in a rat model BioFactors 12 2000 169 174
92. I. Morel, G. Lescoat, P. Cogrel, O. Sergent, N. Pasdeloup, P. Brissot, P. Cillard, and J. Cillard Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures Biochemical Pharmacology 45 1993 13 19
93. A. Murakami, H. Ashida, and J. Terao Multitargeted cancer prevention by quercetin Cancer Letters 269 2008 315 325
94. K. Murota, and J. Terao Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism Archives of Biochemistry and Biophysics 417 2003 12 17
95. C.W. Olanov, and W.G. Tatton Etiology and pathogenesis of Parkinson s disease Annual Review of Neuroscience 22 1999 123 144
96. B. Ossola, T. Kääriäinen, and P.T. Männistö The multiple faces of quercetin in neuroprotection Expert Opinion on Drug Safety 8 2009 397 409
97. Park, E.J.; Pezzuto, J.M.; 2012. Flavonoids In Cancer Prevention. Anticancer Agents in Medicinal Chemistry Jan 31. [Epub ahead of print].
98. C.S. Patil, V.P. Singh, P.S. Satyanarayan, N.K. Jain, A. Singh, and S.K. Kulkarni Protective effect of flavonoids against aging- and lipopolysaccharide- induced cognitive impairment in mice Pharmacology 69 2003 59 67
99. A. Paulke, M. Nöldner, M. Schubert-Zsilavecz, and M. Wurglics St. John's wort flavonoids and their metabolites show antidepressant activity and accumulate in brain after multiple oral doses Pharmazie 63 2008 296 302
100. F. Perez-Vizcaíno, M. Ibarra, A.L. Cogolludo, J. Duarte, F. Zaragoza- Arnaez, L. Moreno, G. Lopez-Lopez, and J. Tamargo Endothelium- independent vasodilator effects of the flavonoid quercetin and its methylated metabolites in rat conductance and resistance arteries Journal of Pharmacology and Experimental Therapeutics 302 2002 66 72
101. S. Priego, F. Feddi, P. Ferrer, S. Mena, M. Benlloch, A. Ortega, J. Carretero, E. Obrador, M. Asensi, and J.M. Estrela Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: a Bcl-2- and superoxide dismutase 2-dependent mechanism Molecular Cancer Therapeutics 7 2008 3330 3342
102. F. Pu, K. Mishima, K. Irie, K. Motohashi, Y. Tanaka, K. Orito, T. Egawa, Y. Kitamura, N. Egashira, K. Iwasaki, and M. Fujiwara Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats Journal of Pharmacological Sciences 104 2007 329 334
103. M. Pytliak, V. Vargová, and V. Mechírová Matrix metalloproteinases and their role in oncogenesis: a review Onkologie 35 2012 49 53
104. ® Planta Medica 76 2010 1683 1690
105. C.A. Rice-Evans, N.J. Miller, and G. Paganga Structure-antioxidant activity relationships of flavonoids and phenolic acids Free Radical Biology and Medicine 20 1996 933 956
106. F. Rivera, G. Costa, A. Abin, J. Urbanavicius, C. Arruti, G. Casanova, and F. Dajas Reduction of ischemic brain damage and increase of glutathione by a liposomal preparation of quercetin in permanent focal ischemia in rats Neurotoxicity Research 13 2008 105 114
107. Ruckenstuhl, C.; Buttner, S.; Carmona-Gutierrez, D.; Eisenberg, T.; Kroemer, G.; Sigrist, S.J.; Fro, K.; Madeo, F.; 2009. The Warburg Effect Suppresses Oxidative Stress Induced Apoptosis in a Yeast Model for Cancer. Plusone, 4, e4592. doi:10.1371/journal.pone.0004592
108. M. Russo, C. Spagnuolo, I. Tedesco, S. Bilotto, and G.L. Russo The flavonoid quercetin in disease prevention and therapy: facts and fancies Biochemical Pharmacology 83 2012 6 15
109. M. Rydén, B. Hempstead, and C.F. Ibáñez Differential modulation of neuron survival during development by nerve growth factor binding to the p75 neurotrophin receptor The Journal of Biological Chemistry 272 1997 16322 16328
110. A.C. Saragusti, M.G. Ortega, J.L. Cabrera, D.A. Estrin, M.A. Marti, and G.A. Chiabrando Inhibitory effect of quercetin on matrix metalloproteinase 9 activity molecular mechanism and structure-activity relationship of the flavonoid-enzyme interaction European Journal of Pharmacology 644 2010 138 145
111. S. Sarkar, and N. Das Mannosylated liposomal flavonoid in combating age-related ischemia-reperfusion induced oxidative damage in rat brain Mechanisms of Ageing and Development 127 2006 391 397
112. S. Schaffer, and B. Halliwell Do polyphenols enter the brain and does it matter? Some theoretical and practical considerations Genes and Nutrition 7 2012 99 109
113. T.E. Schmid, and G. Multhoff Radiation-induced stress proteins - the role of heat shock proteins (HSP) in anti-tumor responses Current Medicinal Chemistry 19 2012 1760 1765
114. E. Schültke, H. Kamencic, V.M. Skihar, R. Griebel, and B. Juurlink Quercetin in an animal model of spinal cord compression injury: correlation of treatment duration with recovery of motor function Spinal Cord 48 2010 112 117
115. 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 hydrolase1 Journal of Nutrition 133 2003 773 776
116. D.B. Shackelford, and R.J. Shaw The LKB1-AMPK pathway: metabolism and growth control in tumour suppression Nature Reviews Cancer 9 2009 563 575
117. R.A. Shanely, A.M. Knab, D.C. Nieman, F. Jin, S.R. McAnulty, and M.J. Landram Quercetin supplementation does not alter antioxidant status in humans Free Radical Research 44 2010 224 231
118. D.A. Shoskes, S.I. Zeitlin, A. Shahed, and J. Rajfer Quercetin in men with category III chronic prostatitis: a preliminary prospective, double blind, and placebo-controlled trial Urology 54 1999 960 963
119. W.S. Smith Pathophysiology of focal cerebral ischemia: a therapeutic perspective Journal of Vascular and Interventional Radiology 15 2004 S3 S12
120. M.R. Spasic, P. Callaerts, and K.K. Norga AMP-activated protein kinase (AMPK) molecular crossroad for metabolic control and survival of neurons Neuroscience 15 2009 309 316
121. J.P.E. Spencer Flavonoids and brain health: multiple effects underpinned by common mechanisms Genes and Nutrition 4 2009 243 250
122. J.P.E. Spencer, G.G.C. Kuhnle, R.J. Williams, and C. Rice Evans Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites Biochemical Journal 372 2003 173 181
123. Takizawa, S.; Fukuyama, N.; Hirabayashi, H.; Kohara, S.; Kazahari, S.; 2003
124. S. Tanigawa, M. Fujii, and D. Hou Stabilization of p53 is involved in quercetin-induced cell cycle arrest and apoptosis in HepG2 cells Bioscience Biotechnology and Biochemistry 72 2008 797 804
125. A.E. Vaughn, and M. Deshmukh Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c Nature Cell Biology 10 2008 1477 1483
126. R. Vidya Priyadarsini, R. Senthil Murugan, S. Maitreyi, K. Ramalingam, D. Karunagaran, and S. Nagini The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition European Journal of Pharmacology 649 2010 84 89
127. M.R. Vijayababu, A. Arunkumar, P. Kanagaraj, P. Venkataraman, G. Krishnamoorthy, and J. Arunakaran Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3) Molecular and Cellular Biochemistry 287 2006 109 116
128. C. Vissiennon, K. Nieber, O. Kelber, and V. Butterweck Route of administration determines the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin - are they prodrugs? The Journal of Nutritional Biochemistry 23 2012 733 740
129. E.H. Walker, M.E. Pacold, O. Perisic, L. Stephens, P.T. Hawkins, M.P. Wymann, and R.L. Williams Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine Molecular and Cellular Biology 6 2000 909 919
130. X. Wang The expanding role of mitochondria in apoptosis Genes and Development 15 2001 2922 2933
131. Y.Q. Wei, X. Zhao, Y. Kariya, H. Fukata, K. Teshigawara, and A. Uchida Induction of apoptosis by quercetin: involvement of heat shock protein Cancer Research 54 1994 4952 4957
132. S. Weinmann, S. Roll, C. Schwarzbach, C. Vauth, and S.N. Willich Effects of Ginkgo biloba in dementia: systematic review and meta- analysis BMC Geriatry 17 2010 10 14
133. R.J. Williams, J.P.E. Spencer, and C. Rice-Evans Flavonoids: antioxidants or signalling molecules? Free Radicals Biology and Medicine 36 2004 838 849
134. G. Williamson, and C. Manach Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention Studies The American Journal of Clinical Nutrition 81 2005 2435 2455
135. W.J. Wilson, and L. Poellinger The dietary flavonoid quercetin modulates HIF-1a activity in endothelial cells Biochemical and Biophysical Research Communications 293 2002 446 450
136. G.J. Wu, W.F. Chen, H.C. Hung, Y.H. Jean, C.S. Sung, C. Chakraborty, H.P. Lee, N.F. Chen, and Z.H. Wen Effects of propofol on proliferation and anti-apoptosis of neuroblastoma SH-SY5Y cell line: new insights into neuroprotection Brain Research 1384 2011 42 50
137. X. Xie, J. Yin, Q. Jia, J. Wang, C. Zou, K.J. Brewer, C. Colombo, Y. Wang, G. Huang, and J. Shen Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt Oncology Reports 26 2010 687 693
138. C.S. Yang, J.M. Landau, M.T. Huang, and H.L. Newmark Inhibition of carcinogenesis by dietary polyphenolic compounds Annual Review of Nutrition 21 2001 381 406
139. M.A. Yenari Heat shock proteins and neuroprotection Advances in Experimental Medicine and Biology 513 2002 281 299
140. K.A. Youdim, M.Z. Qaiser, D.J. Begley, C.A. Rice-Evans, and N.J. Abbott Flavonoid permeability across an in situ model of the blood- brain barrier Free Radicals Biology and Medicine 36 2004 592 604
141. K.A. Youdim, B. Shukitt-Hale, and J.A. Joseph Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system Free Radicals Biology and Medicine 37 2004 1683 1693
142. Z. Yuan, L. Chen, L. Fan, M. Tang, G. Yang, H. Yang, X. Du, G. Wang, W. Yao, Q. Zhao, B. Ye, G.R. Wan, P. Diao, W. Zhang, H. Wu, X. Zhao, and Y. Wei Liposomal quercetin efficiently suppresses growth of solid tumors in murine models Cancer Research 12 2006 3193 3199
143. M. Zhu, J.D. Phillipson, H. Yu, P.M. Greengrass, and N.G. Norman Application of radioligand-receptor binding assays in the search for the active principles of the traditional Chinese medicine 'Gouteng' Phytotherapy Research 11 1997 231 236
144. J. Zielonka, and B. Kalyanaraman ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis critical commentary Free Radicals Biology and Medicine 45 2008 1217 1219