Skip to main content

Advertisement

SpringerLink
Log in

Modulation of Paraoxonase 2 (PON2) in Mouse Brain by the Polyphenol Quercetin: A Mechanism of Neuroprotection?

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Quercetin is a common flavonoid polyphenol which has been shown to exert neuroprotective actions in vitro and in vivo. Though quercetin has antioxidant properties, it has been suggested that neuroprotection may be ascribed to its ability of inducing the cell’s own defense mechanisms. The present study investigated whether quercetin could increase the levels of paraoxonase 2 (PON2), a mitochondrial enzyme expressed in brain cells, which has been shown to have potent antioxidant properties. PON2 protein, mRNA, and lactonase activity were highest in mouse striatal astrocytes. Quercetin increased PON2 levels, possibly by activating the JNK/AP-1 pathway. The increased PON2 levels induced by quercetin resulted in decreased oxidative stress and ensuing toxicity induced by two oxidants. The neuroprotective effect of quercetin was significantly diminished in cells from PON2 knockout mice. These findings suggest that induction of PON2 by quercetin represents an important mechanism by which this polyphenol may exert its neuroprotective action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Arts ICW, Hollman PCH (2005) Polyphenols and disease risk in epidemiological studies. Am J Clin Nutr 81(Suppl.):317S–325S

    PubMed  CAS  Google Scholar 

  2. Kelsey NA, Wilkins HM, Linseman DA (2010) Nutraceutical antioxidants as novel neuroprotective agents. Molecules 15:7792–7814

    Article  PubMed  CAS  Google Scholar 

  3. Scalbert A, Andres-Lacueva C, Arita M, Kroon P, Manach C, Urpi-Sarda M, Wishart D (2011) Databases on food phytochemicals and their health-promoting effects. J Agric Food Chem 59:4331–4348

    Article  PubMed  CAS  Google Scholar 

  4. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658

    Article  PubMed  CAS  Google Scholar 

  5. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795

    Article  PubMed  CAS  Google Scholar 

  6. Martin I, Grotewiel MS (2006) Oxidative damage and age-related functional declines. Mech Aging Dev 127:411–423

    Article  PubMed  CAS  Google Scholar 

  7. USDA (United States Department of Agriculture) (2003) USDA database for the flavonoid content of selected foods. USDA, Beltsville Human Nutrition Research Center, Beltsville, MD

    Google Scholar 

  8. Chen C, Zhou J, Ji C (2010) Quercetin: a potential drug to reverse multidrug resistance. Life Sci 87:333–338

    Article  PubMed  CAS  Google Scholar 

  9. Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC (2007) A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 45:2179–2205

    Article  PubMed  CAS  Google Scholar 

  10. Ossola B, Kaariainen TM, Mannisto PT (2009) The multiple faces of quercetin in neuroprotection. Expert Opin Drug Saf 8:397–409

    Article  PubMed  CAS  Google Scholar 

  11. Mercer LD, Kelly BL, Horne MK, Beart PM (2005) Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis; investigations in primary rat mesencephalic cultures. Biochem Pharmacol 69:339–345

    Article  PubMed  CAS  Google Scholar 

  12. Bournival J, Quessy P, Martinoli MG (2009) Protective effects of resveratrol and quercetin against MPP+-induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cell Mol Neurobiol 29:1169–1180

    Article  PubMed  CAS  Google Scholar 

  13. Bournival J, Plouffe M, Renaud J, Provencher C, Martinoli MG (2012) Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system. Oxidat Med Cell Longev, ID 921941, pp. 11. doi:10.1155/2012/921941

  14. Arredondo F, Echeverry C, Abin-Carriquiry JA, Blasina F, Antunez K, Jones DP, Go YM, Liang YL, Dajas F (2010) After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult. Free Rad Biol Med 49:738–747

    Article  PubMed  CAS  Google Scholar 

  15. Zhang ZJ, Cheang LCV, Wang MW, Lee SMY (2011) Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammatory gene expression in PC-12 cells and in zebrafish. Int J Mol Med 27:195–203

    Article  PubMed  Google Scholar 

  16. Hu P, Wang M, Chen WH, Liu J, Chen L, Yin ST, Yong W, Chen JT, Wang HL, Ruan DY (2008) Quercetin relieves chronic lead exposure-induced impairment of synaptic plasticity in rat dentate gyrus in vivo. Naunyn-Schmiedeberg’s Arch Pharmacol 378:43–51

    Article  CAS  Google Scholar 

  17. Barcelos GRM, Grotto D, Serpeloni JM, Angeli JPF, Rocha BA, Souza VVO, Vicentini JT, Emanuelli T, Bastos JK, Antunes LMG, Knasmuller S, Barbosa F Jr (2011) Protective properties of quercetin against DNA damage and oxidative stress induced by methylmercury in rats. Arch Toxicol 85:1151–1157

    Article  PubMed  CAS  Google Scholar 

  18. Selvakumar K, Bavithra S, Suganthi M, Benson CS, Elumalai P, Arunkumar R, Krishnamoorthy G, Venkataraman P, Arunakaran J (2012) Protective role of quercetin on PCBs-induced oxidative stress and apoptosis in hippocampus of adult rats. Neurochem Res 37:708–721

    Article  PubMed  CAS  Google Scholar 

  19. Lv C, Hong T, yang Z, Zhang Y, Wang L, Dong M, Zhao J, Mu J, Meng Y (2012) Effect of quercetin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson’s disease. Evid Based Complem Altern Med, ID 928643, pp. 6. doi:10.1155/2012/928643

  20. Yao RQ, Qi DS, Yu HL, Liu J, Yang LH, Wu XX (2012) Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3 K/Akt signaling pathway. Neurochem Res 37:2777–2786

    Article  PubMed  CAS  Google Scholar 

  21. Keddy PGW, Dunlop K, Warford J, Samson ML, Jones QRD, Vasantha Rupasinghe HP, Roberstson GS (2012) Neuroprotective and anti-inflammatory effects of the flavonoid-enriched fraction AF4 in a mouse model of hypoxic-ischemic brain injury. PLoS ONE 7(12):e52324. doi:10.1371/journal.pone.0051324

    Article  Google Scholar 

  22. Karuppagounder SS, Madathil SK, Pandey M, Haobam R, Rajamma U, Mohanakumar KP (2013) Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson’s disease in rats. Neuroscience 236:136–148

    Article  PubMed  CAS  Google Scholar 

  23. Boots AW, Haenen GRMM, Bast A (2008) Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 585:325–337

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Halliwell B, Rafter J, Jenner A (2005) Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not? Am J Clin Nutr 81(Suppl.):268S–276S

    PubMed  CAS  Google Scholar 

  26. Pandey KB, Rizvi SI (2009) Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2:270–278

    Article  PubMed  Google Scholar 

  27. Fraga CG, Galleano M, Verstraeten SV, Oteiza PI (2010) Basic biochemical mechanisms behind the health benefits of polyphenols. Mol Aspec Med 31:435–445

    Article  CAS  Google Scholar 

  28. Kay CD (2010) The future of flavonoid research. Br J Nutr 104:S91–S95

    Article  PubMed  CAS  Google Scholar 

  29. Kang JH, Chang SY, Jang HJ, Cho JM, Kim DB, Lee SS, Ko SH, Park YM, Needs PW, Jo YH, Kim MJ (2009) Quercetin-induced upregulation of human GCLC gene is mediated by cis-regulatory element for early growth response protein-1 (EGR1) in INS-1 beta-cells. J Cell Biochem 108:1346–1355

    Article  PubMed  CAS  Google Scholar 

  30. Hayashi Y, Matsushima M, Nakamura T, Shibasaki M, Hashimoto N, Imaizumi K, Shimokata K, Hasegawa Y, Kawabe T (2012) Quercetin protects against pulmonary oxidant stress via heme oxygenase-1 induction in lung epithelial cells. Biochem Biophys Res Commun 417:169–174

    Article  PubMed  CAS  Google Scholar 

  31. Granado-Serrano AB, Martin MA, Bravo L, Goya L, Ramos S (2012) Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: involvement of p38. Chem Biol Interact 195:154–164

    Article  PubMed  CAS  Google Scholar 

  32. Ng CJ, Wadleigh DJ, Gangopadhyyay A, Hama S, Grijalva VR, Navab M, Fogelman AM, Reddy ST (2001) Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 276:44444–44449

    Article  PubMed  CAS  Google Scholar 

  33. Horke S, Witte I, Wilgenbus P, Kruger M, Starnd D, Forstermann U (2007) Paraoxonase-2 reduces oxidative stress in vascular cells and decreases endoplasmic reticulum stress-induced caspase activation. Circulation 115:2055–2064

    Article  PubMed  CAS  Google Scholar 

  34. Horke S, Witte I, Altenhoffer S, Wilgenbus P, Goldeck M, Forstermann U, Xiao J, Kramer GL, Haines DC, Chowdhary PK, Haley RW, Teiber JF (2010) Paraoxonase-2 is down regulated by the Pesudomonas aeruginosa quorum-sensing signal N-(3-oxododecanyl)-L-homoserine lactone and attenuates oxidative stress induced by pyocyanin. Biochem J 426:73–83

    Article  PubMed  CAS  Google Scholar 

  35. Levy E, Trudel K, Bendayan M, Seidman E, Delvin E, Elchebly M, Lavoie JC, Precourt LP, Amre D, Sinnett D (2007) Biological role, protein expression, subcellular localization, and oxidative stress response of paraoxonase 2 in the intestine of human and rats. Am J Physiol Gastrointest Liver Physiol 293:G1252–G1261

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  37. Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN (1996) The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics 33:498–507

    Article  PubMed  CAS  Google Scholar 

  38. Draganov DI, La Du BN (2004) Pharmacogenetics of paraoxonase: a brief review. Naunyn Schmiedebergs Arch Pharmacol 369:78–88

    Article  PubMed  CAS  Google Scholar 

  39. Giordano G, Tait L, Furlong CE, Cole TB, Kavanagh TJ, Costa LG (2013) Gender differences in brain susceptibility to oxidative stress are mediated by levels of paraoxonase-2 expression. Free Rad Biol Med 58:98–108

    Article  PubMed  CAS  Google Scholar 

  40. Higgins GC, Beart PM, Shin YS, Chen MJ, Cheung NS, Nagley P (2010) Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury. J Alzheim Dis 20(Suppl. 2):S453–S473

    Google Scholar 

  41. Devarajan A, Bourquard N, Hama S, Navab M, Grijalva VR, Morvardi S, Clarke C, Vergnes L, Reue K, Teiber JF, Reddy ST (2011) Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis. Antiox Redox Signal 14:341–351

    Article  CAS  Google Scholar 

  42. Costa LG, Giordano G, Furlong CE (2011) Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: the hunt goes on. Biochem Pharmacol 81:337–344

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  44. Fuhrman B, Khateeb J, Shiner M, Nitzan O, Karry R, Volkova N, Aviram M (2008) Urokinase plasminogen activator upregulates paraoxonase 2 expression in macrophages via an NADPH oxidase-dependent mechanism. Arterioscler Thromb Vasc Res 28:1361–1367

    Article  CAS  Google Scholar 

  45. Fuhrman B, Gantman A, Khateeb J, Volkova N, Horke S, Kiyan J, Dumler I, Aviram M (2009) Urokinase activates macrophage PON2 gene transcription via the PI3 K/ROS/MEK/SREBP-2 signalling cascade mediated by the PDGFR-beta. Cardiovasc Res 84:145–154

    Article  PubMed  CAS  Google Scholar 

  46. Rosenblat M, Volkova N, Roqueta-Rovera M, Nakamura MT, Aviram M (2010) Increased macrophage cholesterol biosysnthesis and decreased cellular paraoxonase 2 (PON2) expression in Δ6-desaturase knockout (6-DS-KO) mice: beneficial effects of arachidonic acid. Atherosclerosis 210:414–421

    Article  PubMed  CAS  Google Scholar 

  47. Shiner M, Fuhrman B, Aviram M (2007) Macrophage paraoxonase 2 (PON2) expression is upregulated by unesterified cholesterol through activation of the phosphatidylinositol 3-kinase (PI3 K) pathway. Biol Chem 388:1353–1358

    Article  PubMed  CAS  Google Scholar 

  48. Yehuda I, Madar Z, Szuchman-Sapir A, Tamir S (2011) Glabridin, a phytoestrogen from licorice root, up-regulates manganese superoxide dismutase, catalase and paraoxonase 2 under glucose stress. Phytother Res 25:659–667

    PubMed  CAS  Google Scholar 

  49. Rosenblat M, Hayek T, Hussein K, Aviram M (2004) Decreased macrophage paraoxonase 2 expression in patients with hypercholesterolemia is the result of their increased cellular cholesterol content: effect of atorvastatin therapy. Arterioscler Thromb Vasc Biol 24:175–180

    Article  PubMed  CAS  Google Scholar 

  50. Shiner M, Fuhrman B, Aviram M (2007) Macrophage paraoxonase 2 (PON2) expression is up-regulated by pomegranate juice phenolic anti-oxidants via PPARγ and AP-1 pathway activation. Atherosclerosis 195:313–321

    Article  PubMed  CAS  Google Scholar 

  51. Stucker Fernandez E, de Oliveira Machado M, Minuzzi Becker A, de Andrade F, Maraschin M, Luiz da Silva E (2012) Yerba mate (Ilex paraguariensis) enhances the gene modulation and activity of paraoxonase-2: in vitro and in vivo studies. Nutrition 28:1157–1164

    Article  Google Scholar 

  52. Boesch-Saadatmandi C, Pospissil RT, Graeser AC, Canali R, Boomgaarden I, Doering F, Wolffram S, Egert S, Mueller MJ, Rimbach G (2009) Effect of quercetin on paraoxonase 2 levels in RAW264.7 macrophages and in human monocytes—role of quercetin metabolism. Int J Mol Sci 10:4168–4177

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  54. Ott M, Gogvadze V, Orrenius S, Zhivotovsky B (2007) Mitochondria, oxidative stress and cell death. Apoptosis 12:913–922

    Article  PubMed  CAS  Google Scholar 

  55. Altenhofer S, Witte I, Teiber JF, Wilgenbus P, Pautz A, Li H, Daiber A, Witan H, Clement AM, Forstermann U, Horke S (2010) One enzyme, two functions. PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity. J Biol Chem 285:24398–24403

    Article  PubMed  Google Scholar 

  56. Fiorani M, Guidarelli A, Blasa M, Azzolini C, Candiracci M, Piatti E, Cantoni O (2010) Mitochondria accumulate large amounts of quercetin: prevention of mitochondrial damage and release upon oxidation of the extramitochondrial fraction of the flavonoid. J Nutr Biochem 21:397–404

    Article  PubMed  CAS  Google Scholar 

  57. Notas G, Nifli AP, Kampa M, Pelekanou V, Alexaki VI, Theodoropoulos P, Vercauteren J, Castanas E (2012) Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells. J Nutr Biochem 23:656–666

    Article  PubMed  CAS  Google Scholar 

  58. Jones QRD, Warford J, Vasantha Rupasinghe HP, Robertson GS (2012) Target-based selection of flavonoids for neurodegenerative disorders. Trends Pharmacol Sci 33:602–610

    Article  PubMed  CAS  Google Scholar 

  59. Mehan S, Meena H, Sharma D, Sankhla R (2011) JNK: a stress-activated protein kinase therapeutic strategies and involvement in Alzheimer’s and various neurodegenerative abnormalities. J Mol Neurosci 43:376–390

    Article  PubMed  CAS  Google Scholar 

  60. Weston CR, Davis RJ (2007) The JNK signal transduction pathway. Curr Opin Cell Biol 19:142–149

    Article  PubMed  CAS  Google Scholar 

  61. Holst B, Williamson G (2008) Nutrients and phytochemicals: from bioavailability to bioefficacy beyond antioxidants. Curr Opin Biotechnol 19:73–82

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  63. Chang YF, Hsu YC, Hung HF, Lee HJ, Lui WY, Chi CW, Wang JJ (2009) Quercetin induces oxidative stress and potentiates the apoptotic action of 2-methoxyestradiol in human hepatoma cells. Nutr Cancer 61:735–745

    Article  PubMed  CAS  Google Scholar 

  64. Granado-Serrano AB, Martin MA, Bravo L, Goya L, Ramos S (2010) Quercetin modulates Nf-kB and AP-1/JNK pathways to induce cell death in human hepatoma cells. Nutr Cancer 62:390–401

    Article  PubMed  CAS  Google Scholar 

  65. Miodini P, Fioravanti L, Di Fronzo G, Cappelletti V (1999) The two phyto-estrogens genistein and quercetin exert different effects on oestrogen receptor function. Br J Cancer 80:1150–1155

    Article  PubMed  CAS  Google Scholar 

  66. van der Woude H, ter Veld MGR, Jacobs N, van der Saag PT, Murk AJ, Rietjens IMCM (2005) The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor. Mol Nutr Food Res 49:763–771

    Article  PubMed  Google Scholar 

  67. Galluzzo P, Martini C, Bulzomi P, Leone S, Bolli A, Pallottini V, Marino M (2009) Quercetin-induced apoptotic cascade in cancer cells: antioxidant versus estrogen receptor alpha-dependent mechanisms. Mol Nutr Food Res 53:699–708

    Article  PubMed  CAS  Google Scholar 

  68. Bulzomi P, Galluzzo P, Bolli A, Leone S, Acconcia F, Marino M (2011) The pro-apoptotic effect of quercetin in cancer cell lines requires ERβ-dependent signals. J Cell Physiol 227:1891–1898

    Article  Google Scholar 

  69. Hollman PC, deVries JH, van Leeuwen SD, Mengelers MJ, Katan MB (1995) Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr 62:1276–1282

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  72. Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ (2004) Flavonoid permeability across an in situ model of the blood-brain barrier. Free Rad Biol Med 36:592–604

    Article  PubMed  CAS  Google Scholar 

  73. Faria A, Pestana D, Teixera D, Azevedo J, De Freitas V, Mateus N, Calhau C (2010) Flavonoid transport across RBE4 cells: a blood-brain barrier model. Cell Mol Biol Lett 15:234–241

    Article  PubMed  CAS  Google Scholar 

  74. Ishisaka A, Ichikawa S, Sakakibara H, Piskula MK, Nakamura T, Kato Y, Ito M, Miyamoto K, Tsuji A, Kawai Y, Terao J (2011) Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats. Free Rad Biol Med 51:329–336

    Article  Google Scholar 

  75. deBoer VCJ, Dihal AA, van der Woude H, Arts ICW, Wolffram A, Alink GM, Rietjens IMCM, Keijer J, Hollma PCH (2005) Tissue distribution of quercetin in rats and pigs. J Nutr 135:1718–1725

    CAS  Google Scholar 

  76. Bieger J, Cermak R, Blank R, deBoer VCJ, Hollman PCH, Kamphues J, Wolffram S (2008) Tissue distribution of quercetin in pigs after long-term dietary supplementation. J Nutr 138:1417–1420

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  78. Russo M, Spagnuolo C, Tedesco I, Bilotto S, Russo GM (2012) The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem Pharmacol 83:6–15

    Article  PubMed  CAS  Google Scholar 

  79. Dajas F, Rivera-Megret F, Blasina F, Arredondo F, Abin-Carriquiry JA, Costa G, Echeverry C, Lafon L, Heizen H, Ferreira M, Morquio A (2003) Neuroprotection by flavonoids. Braz J Med Biol Res 36:1613–1620

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  82. Day AJ, Mellon F, Barron D, Sarrazin G, Morgan MRA, Williamson G (2001) Human metabolism of dietary flavonoids: identification of plasma metabolites of quercetin. Free Rad. Res. 35:941–952

    Article  CAS  Google Scholar 

  83. Fiorani M, Accorsi A, Cantoni O (2003) Human red blood cells as a natural flavonoid reservoir. Free Rad Res 37:1331–1338

    Article  CAS  Google Scholar 

  84. Verzelloni E, Pellacani C, Tagliazucchi D, Tagliaferri S, Calani L, Costa LG, Brighenti F, Borges G, Crozier A, Conte A, Del Rio D (2011) Antiglycative and neuroprotective activity of colon-derived polyphenol catabolites. Mol Nutr Food Res 55:1–9

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported in part by Grants P42ES04696 and P30ES07033 from the National Institute of Environmental Health Sciences, and P30HD02274 from the National Institute of Child Health and Human Development. We thank Dr. Fred Farin and Jasmine Wilkerson from the Functional Genomics and Proteomics Facility in the Dept. of Environmental and Occupational Health Sciences at the University of Washington for measuring PON2 mRNA levels.

Author information

Authors and Affiliations

  1. Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA, 98105, USA

    Lucio G. Costa, Leah Tait, Rian de Laat, Khoi Dao, Gennaro Giordano & Toby B. Cole

  2. Center on Human Development and Disability, University of Washington, Seattle, WA, USA

    Toby B. Cole

  3. Division of Medical Genetics, Department of Genome Sciences, University of Washington, Seattle, WA, USA

    Toby B. Cole & Clement E. Furlong

  4. Department of Neuroscience, University of Parma, Parma, Italy

    Lucio G. Costa & Claudia Pellacani

Authors
  1. Lucio G. Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leah Tait
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rian de Laat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Khoi Dao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gennaro Giordano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Claudia Pellacani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toby B. Cole
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Clement E. Furlong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lucio G. Costa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Costa, L.G., 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 38, 1809–1818 (2013). https://doi.org/10.1007/s11064-013-1085-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-013-1085-1

Keywords

Search

Navigation