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Effects of Polyphenols on Brain Ageing and Alzheimer’s Disease: Focus on Mitochondria

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Abstract

The global trend of the phenomenon of population ageing has dramatic consequences on public health and the incidence of neurodegenerative diseases. Physiological changes that occur during normal ageing of the brain may exacerbate and initiate pathological processes that may lead to neurodegenerative disorders, especially Alzheimer's disease (AD). Hence, the risk of AD rises exponentially with age. While there is no cure currently available, sufficient intake of certain micronutrients and secondary plant metabolites may prevent disease onset. Polyphenols are highly abundant in the human diet, and several experimental and epidemiological evidences indicate that these secondary plant products have beneficial effects on AD risks. This study reviews current knowledge on the potential of polyphenols and selected polyphenol-rich diets on memory and cognition in human subjects, focusing on recent data showing in vivo efficacy of polyphenols in preventing neurodegenerative events during brain ageing and in dementia. Concentrations of polyphenols in animal brains following oral administration have been consistently reported to be very low, thus eliciting controversial discussion on their neuroprotective effects and potential mechanisms. Whether polyphenols exert any direct antioxidant effects in the brain or rather act by evoking alterations in regulatory systems of the brain or even the body periphery is still unclear. To understand the mechanisms behind the protective abilities of polyphenol-rich foods, an overall understanding of the biotransformation of polyphenols and identification of the various metabolites arising in the human body is also urgently needed.

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References

  1. Armentano L, Bentsath T, Beres T, Rusznayak S, Szent-Györgyi (1936) Über den Einfluß von Substanzen der Flavongruppe auf die Permeabilität der Kapillaren. Vitamin P. Dtsch Med Wochenschr 63(33):1325–1328

    Article  Google Scholar 

  2. Beiler JM, Martin GJ (1947) Inhibitory action of vitamin P compounds on hyaluronidase. J Biol Chem 171(2):507–511

    PubMed  CAS  Google Scholar 

  3. Spencer JP (2010) The impact of fruit flavonoids on memory and cognition. Br J Nutr 104(Suppl 3):S40–S47

    Article  PubMed  CAS  Google Scholar 

  4. Pasinetti GM, Wang J, Porter S, Ho L (2011) Caloric intake, dietary lifestyles, macronutrient composition, and alzheimer' disease dementia. Int J Alzheimers Dis 2011:806293

    PubMed  Google Scholar 

  5. Visioli F, Davalos A (2011) Polyphenols and cardiovascular disease: a critical summary of the evidence. Mini Rev Med Chem 11(14):1186–1190

    PubMed  CAS  Google Scholar 

  6. Park EJ, Pezzuto JM (2012) Flavonoids in cancer prevention. Anticancer Agents Med Chem

  7. Scalbert A, Manach C, Morand C, Remesy C, Jimenez L (2005) Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 45(4):287–306

    Article  PubMed  CAS  Google Scholar 

  8. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79(5):727–747

    PubMed  CAS  Google Scholar 

  9. Scalbert A, Williamson G (2000) Dietary Intake and bioavailability of polyphenols. J Nutr 130(8):2073S–2085S

    PubMed  CAS  Google Scholar 

  10. Hollman PCH, Arts ICW (2000) Flavonols, flavones and flavanols—nature, occurrence and dietary burden. J Sci Food Agric 80(7):1081–1093

    Article  CAS  Google Scholar 

  11. Long LH, Clement MV, Halliwell B (2000) Artifacts in cell culture: rapid generation of hydrogen peroxide on addition of (−)-epigallocatechin, (−)-epigallocatechin gallate, (+)-catechin, and quercetin to commonly used cell culture media. Biochem Biophys Res Commun 273(1):50–53

    Article  PubMed  CAS  Google Scholar 

  12. Long LH, Hoi A, Halliwell B (2010) Instability of, and generation of hydrogen peroxide by, phenolic compounds in cell culture media. Arch Biochem Biophys 501(1):162–169

    Article  PubMed  CAS  Google Scholar 

  13. Forman HJ (2007) Use and abuse of exogenous H2O2 in studies of signal transduction. Free Radic Biol Med 42(7):926–932

    Article  PubMed  CAS  Google Scholar 

  14. Veal E, Day A (2011) Hydrogen peroxide as a signaling molecule. Antioxid Redox Signal 15(1):147–151

    Article  PubMed  CAS  Google Scholar 

  15. Long LH, Halliwell B (2009) Artefacts in cell culture: pyruvate as a scavenger of hydrogen peroxide generated by ascorbate or epigallocatechin gallate in cell culture media. Biochem Biophys Res Commun 388(4):700–4

    Article  PubMed  CAS  Google Scholar 

  16. Muller WE, Eckert A, Kurz C, Eckert GP, Leuner K (2010) Mitochondrial dysfunction: common final pathway in brain aging and Alzheimer's disease—therapeutic aspects. Mol Neurobiol 41(2–3):159–171

    Article  PubMed  CAS  Google Scholar 

  17. Nijtmans LGJ, Ugallde C, van den Heuvel LP, Smeitink JAM (2004) Function and dysfunction of the oxidative phospharylation system. In: Koehler C, Bauer MF (eds) Mitochondrial function and biogenetics. Springer Inc., Heidelberg, pp 149–167

    Chapter  Google Scholar 

  18. Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, Pakay JL, Parker N (2004) Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 37(6):755–767

    Article  PubMed  CAS  Google Scholar 

  19. Smeitink J, van den Heuvel L, DiMauro S (2001) The genetics and pathology of oxidative phosphorylation. Nat Rev Genet 2(5):342–352

    Article  PubMed  CAS  Google Scholar 

  20. Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK, Hill DE, Vidal M, Evans JG, Thorburn DR, Carr SA, Mootha VK (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134(1):112–123

    Article  PubMed  CAS  Google Scholar 

  21. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38(5):515–517

    Article  PubMed  CAS  Google Scholar 

  22. Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, Khrapko K (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 38(5):518–520

    Article  PubMed  CAS  Google Scholar 

  23. Gimenez-Roqueplo AP, Favier J, Rustin P, Mourad JJ, Plouin PF, Corvol P, Rotig A, Jeunemaitre X (2001) The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am J Hum Genet 69(6):1186–1197

    Article  PubMed  CAS  Google Scholar 

  24. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13

    Article  PubMed  CAS  Google Scholar 

  25. Harper ME, Bevilacqua L, Hagopian K, Weindruch R, Ramsey JJ (2004) Ageing, oxidative stress, and mitochondrial uncoupling. Acta Physiol Scand 182(4):321–331

    Article  PubMed  CAS  Google Scholar 

  26. Kudin AP, Bimpong-Buta NY, Vielhaber S, Elger CE, Kunz WS (2004) Characterization of superoxide-producing sites in isolated brain mitochondria. J Biol Chem 279(6):4127–4135

    Article  PubMed  CAS  Google Scholar 

  27. Murphy MP (2009) Mitochondria—a neglected drug target. Curr Opin Investig Drugs 10(10):1022–1024

    PubMed  CAS  Google Scholar 

  28. Fukai T, Ushio-Fukai M (2011) Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 15(6):1583–1606

    Article  PubMed  CAS  Google Scholar 

  29. Marchetti P, Castedo M, Susin SA, Zamzami N, Hirsch T, Macho A, Haeffner A, Hirsch F, Geuskens M, Kroemer G (1996) Mitochondrial permeability transition is a central coordinating event of apoptosis. J Exp Med 184(3):1155–1160

    Article  PubMed  CAS  Google Scholar 

  30. Martinou JC, Youle RJ (2011) Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell 21(1):92–101

    Article  PubMed  CAS  Google Scholar 

  31. Rasola A, Sciacovelli M, Pantic B, Bernardi P (2010) Signal transduction to the permeability transition pore. FEBS Lett 584(10):1989–1996

    Article  PubMed  CAS  Google Scholar 

  32. Napoli E, Taroni F, Cortopassi GA (2006) Frataxin, iron-sulfur clusters, heme, ROS, and aging. Antioxid Redox Signal 8(3–4):506–516

    Article  PubMed  CAS  Google Scholar 

  33. Bilsland LG, Nirmalananthan N, Yip J, Greensmith L, Duchen MR (2008) Expression of mutant SOD1 in astrocytes induces functional deficits in motoneuron mitochondria. J Neurochem 107(5):1271–1283

    Article  PubMed  CAS  Google Scholar 

  34. Casley CS, Land JM, Sharpe MA, Clark JB, Duchen MR, Canevari L (2002) Beta-amyloid fragment 25–35 causes mitochondrial dysfunction in primary cortical neurons. Neurobiol Dis 10(3):258–267

    Article  PubMed  CAS  Google Scholar 

  35. Mattson MP, Chan SL, Duan W (2002) Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev 82(3):637–672

    PubMed  CAS  Google Scholar 

  36. Mattson MP, Magnus T (2006) Ageing and neuronal vulnerability. Nat Rev Neurosci 7(4):278–294

    Article  PubMed  CAS  Google Scholar 

  37. Genova ML, Pich MM, Bernacchia A, Bianchi C, Biondi A, Bovina C, Falasca AI, Formiggini G, Castelli GP, Lenaz G (2004) The mitochondrial production of reactive oxygen species in relation to aging and pathology. Ann N Y Acad Sci 1011:86–100

    Article  PubMed  CAS  Google Scholar 

  38. Reddy PH, Reddy TP (2011) Mitochondria as a therapeutic target for aging and neurodegenerative diseases. Curr Alzheimer Res 8(4):393–409

    Article  PubMed  CAS  Google Scholar 

  39. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495

    Article  PubMed  CAS  Google Scholar 

  40. Benzi G, Pastoris O, Marzatico F, Villa RF, Dagani F, Curti D (1992) The mitochondrial electron transfer alteration as a factor involved in the brain aging. Neurobiol Aging 13(3):361–368

    Article  PubMed  CAS  Google Scholar 

  41. Stoll S, Scheuer K, Pohl O, Muller WE (1996) Ginkgo biloba extract (EGb 761) independently improves changes in passive avoidance learning and brain membrane fluidity in the aging mouse. Pharmacopsychiatry 29(4):144–149

    PubMed  CAS  Google Scholar 

  42. Ruggiero FM, Cafagna F, Petruzzella V, Gadaleta MN, Quagliariello E (1992) Lipid composition in synaptic and nonsynaptic mitochondria from rat brains and effect of aging. J Neurochem 59(2):487–491

    Article  PubMed  CAS  Google Scholar 

  43. Eckert GP, Wood WG, Mueller WE (2001) Effects of aging and beta-amyloid on the properties of brain synaptic and mitochondrial membranes. J Neural Transm 108(8–9):1051–1064

    Article  PubMed  CAS  Google Scholar 

  44. Ochoa JJ, Pamplona R, Ramirez-Tortosa MC, Granados-Principal S, Perez-Lopez P, Naudi A, Portero-Otin M, Lopez-Frias M, Battino M, Quiles JL (2011) Age-related changes in brain mitochondrial DNA deletion and oxidative stress are differentially modulated by dietary fat type and coenzyme Q. Free Radic Biol Med 50(9):1053–1064

    Article  PubMed  CAS  Google Scholar 

  45. Navarro A, Boveris A (2007) The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 292(2):C670–C686

    Article  PubMed  CAS  Google Scholar 

  46. Lenaz G, Bovina C, Castelluccio C, Fato R, Formiggini G, Genova ML, Marchetti M, Pich MM, Pallotti F, Parenti CG, Biagini G (1997) Mitochondrial complex I defects in aging. Mol Cell Biochem 174(1–2):329–333

    Article  PubMed  CAS  Google Scholar 

  47. Atamna H, Frey WH (2007) Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion 7(5):297–310

    Article  PubMed  CAS  Google Scholar 

  48. Martinez M, Ferrandiz ML, De Juan E, Miquel J (1994) Age-related changes in glutathione and lipid peroxide content in mouse synaptic mitochondria: relationship to cytochrome c oxidase decline. Neurosci Lett 170(1):121–124

    Article  PubMed  CAS  Google Scholar 

  49. Perluigi M, Di Domenico F, Giorgi A, Schinina ME, Coccia R, Cini C, Bellia F, Cambria MT, Cornelius C, Butterfield DA, Calabrese V (2010) Redox proteomics in aging rat brain: involvement of mitochondrial reduced glutathione status and mitochondrial protein oxidation in the aging process. J Neurosci Res 88(16):3498–3507

    Article  PubMed  CAS  Google Scholar 

  50. Richter C, Park JW, Ames BN (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci U S A 85(17):6465–6467

    Article  PubMed  CAS  Google Scholar 

  51. Chomyn A, Attardi G (2003) MtDNA mutations in aging and apoptosis. Biochem Biophys Res Commun 304(3):519–529

    Article  PubMed  CAS  Google Scholar 

  52. Yao J, Hamilton RT, Cadenas E, Brinton RD (2010) Decline in mitochondrial bioenergetics and shift to ketogenic profile in brain during reproductive senescence. Biochim Biophys Acta 1800(10):1121–1126

    Article  PubMed  CAS  Google Scholar 

  53. Wimo A, Winblad B, Aguero-Torres H, von Strauss E (2003) The magnitude of dementia occurrence in the world. Alzheimer Dis Assoc Disord 17(2):63–67

    Article  PubMed  Google Scholar 

  54. Qiu C, Kivipelto M, von Strauss E (2009) Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci 11(2):111–128

    PubMed  Google Scholar 

  55. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366(9503):2112–2117

    Article  PubMed  Google Scholar 

  56. Qiu C, De Ronchi D, Fratiglioni L (2007) The epidemiology of the dementias: an update. Curr Opin Psychiatry 20(4):380–385

    Article  PubMed  Google Scholar 

  57. Ziegler-Graham K, Brookmeyer R, Johnson E, Arrighi HM (2008) Worldwide variation in the doubling time of Alzheimer's disease incidence rates. Alzheimers Dement 4(5):316–323

    Article  PubMed  Google Scholar 

  58. Arendt T (2009) Synaptic degeneration in Alzheimer's disease. Acta Neuropathol 118(1):167–179

    Article  PubMed  Google Scholar 

  59. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 14(8):837–842

    Article  PubMed  CAS  Google Scholar 

  60. Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, Klein WL (2007) Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci 27(4):796–807

    Article  PubMed  CAS  Google Scholar 

  61. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8(2):101–112

    Article  PubMed  CAS  Google Scholar 

  62. Manczak M, Park BS, Jung Y, Reddy PH (2004) Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease: implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med 5(2):147–162

    Article  PubMed  CAS  Google Scholar 

  63. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15(9):1437–1449

    Article  PubMed  CAS  Google Scholar 

  64. Valla J, Berndt JD, Gonzalez-Lima F (2001) Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration. J Neurosci 21(13):4923–4930

    PubMed  CAS  Google Scholar 

  65. Schioth HB, Craft S, Brooks SJ, Frey WH, 2nd, Benedict C (2012) Brain insulin signaling and Alzheimer's disease: current evidence and future directions. Mol Neurobiol. doi:10.1007/s12035-011-8229-6

  66. Mattson MP, Gleichmann M, Cheng A (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60(5):748–766

    Article  PubMed  CAS  Google Scholar 

  67. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer's disease. J Neurosci 21(9):3017–3023

    PubMed  CAS  Google Scholar 

  68. Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci 29(28):9090–9103

    Article  PubMed  CAS  Google Scholar 

  69. Rhein V, Song X, Wiesner A, Ittner LM, Baysang G, Meier F, Ozmen L, Bluethmann H, Drose S, Brandt U, Savaskan E, Czech C, Gotz J, Eckert A (2009) Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice. Proc Natl Acad Sci U S A 106(47):20057–20062

    PubMed  CAS  Google Scholar 

  70. Keil U, Hauptmann S, Bonert A, Scherping I, Eckert A, Muller WE (2006) Mitochondrial dysfunction induced by disease relevant AbetaPP and tau protein mutations. J Alzheimers Dis 9(2):139–146

    PubMed  Google Scholar 

  71. Leuner K, Schutt T, Kurz C, Eckert SH, Schiller C, Occhipinti A, Mai S, Jendrach M, Eckert GP, Kruse SE, Palmiter RD, Brandt U, Drose S, Wittig I, Willem M, Haass C, Reichert AS, Mueller WE (2012) Mitochondria-derived ROS lead to enhanced amyloid beta formation. Antioxid Redox Signal 16(12):1421–1433

    Google Scholar 

  72. Grant SM, Shankar SL, Chalmers-Redman RM, Tatton WG, Szyf M, Cuello AC (1999) Mitochondrial abnormalities in neuroectodermal cells stably expressing human amyloid precursor protein (hAPP751). Neuroreport 10(1):41–46

    Article  PubMed  CAS  Google Scholar 

  73. Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG (2003) Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol 161(1):41–54

    Article  PubMed  CAS  Google Scholar 

  74. Keil U, Bonert A, Marques CA, Scherping I, Weyermann J, Strosznajder JB, Muller-Spahn F, Haass C, Czech C, Pradier L, Muller WE, Eckert A (2004) Amyloid beta-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis. J Biol Chem 279(48):50310–50320

    Article  PubMed  CAS  Google Scholar 

  75. Hansson CA, Frykman S, Farmery MR, Tjernberg LO, Nilsberth C, Pursglove SE, Ito A, Winblad B, Cowburn RF, Thyberg J, Ankarcrona M (2004) Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria. J Biol Chem 279(49):51654–51660

    Article  PubMed  CAS  Google Scholar 

  76. Kamphuis PJ, Scheltens P (2010) Can nutrients prevent or delay onset of Alzheimer's disease? J Alzheimers Dis 20(3):765–775

    PubMed  Google Scholar 

  77. Visioli F (2012) Can experimental pharmacology be always applied to human nutrition? Int J Food Sci Nutr 63(suppl 1):10–13

    Article  PubMed  CAS  Google Scholar 

  78. Oeppen J, Vaupel JW (2002) Demography. Broken limits to life expectancy. Science 296(5570):1029–1031

    Article  PubMed  CAS  Google Scholar 

  79. Brody JA, Schneider EL (1986) Diseases and disorders of aging: an hypothesis. J Chronic Dis 39(11):871–876

    Article  PubMed  CAS  Google Scholar 

  80. Fulop T, Larbi A, Witkowski JM, McElhaney J, Loeb M, Mitnitski A, Pawelec G (2010) Aging, frailty and age-related diseases. Biogerontology 11(5):547–563

    Article  PubMed  CAS  Google Scholar 

  81. Schaffer S, Eckert GP, Schmitt-Schillig S, Muller WE (2006) Plant foods and brain aging: a critical appraisal. Forum Nutr 59:86–115

    Article  PubMed  CAS  Google Scholar 

  82. Rattan SI (2006) Theories of biological aging: genes, proteins, and free radicals. Free Radic Res 40(12):1230–1238

    Article  PubMed  CAS  Google Scholar 

  83. Kennedy DO, Wightman EL (2011) Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Adv Nutr 2(1):32–50

    PubMed  CAS  Google Scholar 

  84. Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues JF (2000) Intake of flavonoids and risk of dementia. Eur J Epidemiol 16(4):357–363

    Article  PubMed  CAS  Google Scholar 

  85. Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P (2007) Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 165(12):1364–1371

    Article  PubMed  CAS  Google Scholar 

  86. Kesse-Guyot E, Fezeu L, Andreeva VA, Touvier M, Scalbert A, Hercberg S, Galan P (2012) Total and specific polyphenol intakes in midlife are associated with cognitive function measured 13 years later. J Nutr 142(1):76–83

    Article  PubMed  CAS  Google Scholar 

  87. Spencer JP (2003) Metabolism of tea flavonoids in the gastrointestinal tract. J Nutr 133(10):3255S–3261S

    PubMed  CAS  Google Scholar 

  88. Barnes S, Prasain J, D'Alessandro T, Arabshahi A, Botting N, Lila MA, Jackson G, Janle EM, Weaver CM (2011) The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems. Food Funct 2(5):235–244

    Article  PubMed  CAS  Google Scholar 

  89. Nemeth K, Plumb GW, Berrin JG, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) 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(1):29–42

    Article  PubMed  CAS  Google Scholar 

  90. Hollman PC, de Vries 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(6):1276–1282

    PubMed  CAS  Google Scholar 

  91. Sang S, Lambert JD, Ho CT, Yang CS (2011) The chemistry and biotransformation of tea constituents. Pharmacol Res 64(2):87–99

    Article  PubMed  CAS  Google Scholar 

  92. Wu B, Kulkarni K, Basu S, Zhang S, Hu M (2011) First-pass metabolism via UDP-glucuronosyltransferase: a barrier to oral bioavailability of phenolics. J Pharm Sci 100(9):3655–3681

    Article  PubMed  CAS  Google Scholar 

  93. Kay CD, Kroon PA, Cassidy A (2009) The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53(S1):S92–S101

    Article  PubMed  Google Scholar 

  94. Kahle K, Huemmer W, Kempf M, Scheppach W, Erk T, Richling E (2007) Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption. J Agric Food Chem 55(26):10605–10614

    Article  PubMed  CAS  Google Scholar 

  95. Schantz M, Erk T, Richling E (2010) Metabolism of green tea catechins by the human small intestine. Biotechnol J 5(10):1050–1059

    Article  PubMed  CAS  Google Scholar 

  96. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J (2010) Mood and gut feelings. Brain Behav Immun 24(1):9–16

    Article  PubMed  Google Scholar 

  97. van Duynhoven J, Vaughan EE, Jacobs DM, Kemperman RA, van Velzen EJ, Gross G, Roger LC, Possemiers S, Smilde AK, Dore J, Westerhuis JA, Van de Wiele T (2011) Metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci U S A 108(Suppl 1):4531–4538

    Article  PubMed  Google Scholar 

  98. Rhee SH, Pothoulakis C, Mayer EA (2009) Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol 6(5):306–314

    Article  PubMed  CAS  Google Scholar 

  99. Paulke A, Eckert GP, Schubert-Zsilavecz M, Wurglics M (2012) Isoquercitrin provides better bioavailability than pure quercetin: comparison of quercetin metabolites in body tissue and brain sections after six day administration of isoquercitrin and quercetin. Pharmazie (in press)

  100. Rangel-Ordonez L, Noldner M, Schubert-Zsilavecz M, Wurglics M (2010) Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb 761(R). Planta Med 76(15):1683–1690

    Article  PubMed  CAS  Google Scholar 

  101. Paulke A, Noldner M, Schubert-Zsilavecz M, Wurglics M (2008) St. John's wort flavonoids and their metabolites show antidepressant activity and accumulate in brain after multiple oral doses. Pharmazie 63(4):296–302

    PubMed  CAS  Google Scholar 

  102. 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 

  103. Friden M, Bergstrom F, Wan H, Rehngren M, Ahlin G, Hammarlund-Udenaes M, Bredberg U (2011) Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods. Drug Metab Dispos 39(3):353–362

    Article  PubMed  CAS  Google Scholar 

  104. Colovic M, Fracasso C, Caccia S (2008) Brain-to-plasma distribution ratio of the biflavone amentoflavone in the mouse. Drug Metab Lett 2(2):90–94

    Article  PubMed  CAS  Google Scholar 

  105. Nakagawa K, Miyazawa T (1997) Absorption and distribution of tea catechin, (−)-epigallocatechin-3-gallate, in the rat. J Nutr Sci Vitaminol (Tokyo) 43(6):679–684

    Article  CAS  Google Scholar 

  106. Abd El Mohsen MM, Kuhnle G, Rechner AR, Schroeter H, Rose S, Jenner P, Rice-Evans CA (2002) Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic Biol Med 33(12):1693–1702

    Article  PubMed  CAS  Google Scholar 

  107. Talavera S, Felgines C, Texier O, Besson C, Gil-Izquierdo A, Lamaison J-L, Remesy C (2005) Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. J Agric Food Chem 53(10):3902–3908

    Article  PubMed  CAS  Google Scholar 

  108. de Boer VC, Dihal AA, van der Woude H, Arts IC, Wolffram S, Alink GM, Rietjens IM, Keijer J, Hollman PC (2005) Tissue distribution of quercetin in rats and pigs. J Nutr 135(7):1718–1725

    PubMed  Google Scholar 

  109. Keys A (1995) Mediterranean diet and public health: personal reflections. Am J Clin Nutr 61(6):1321S–1323S

    PubMed  CAS  Google Scholar 

  110. Noah A, Truswell AS (2001) There are many Mediterranean diets. Asia Pac J Clin Nutr 10(1):2–9

    Article  PubMed  CAS  Google Scholar 

  111. Feart C, Samieri C, Barberger-Gateau P (2010) Mediterranean diet and cognitive function in older adults. Curr Opin Clin Nutr Metab Care 13(1):14–18

    Article  PubMed  CAS  Google Scholar 

  112. Panza F, Solfrizzi V, Colacicco AM, D'Introno A, Capurso C, Torres F, Del PA, Capurso S, Capurso A (2004) Mediterranean diet and cognitive decline. Public Health Nutr 7(7):959–963

    Article  PubMed  CAS  Google Scholar 

  113. Gardner CD, Kraemer HC (1995) Monounsaturated versus polyunsaturated dietary fat and serum lipids. A meta-analysis. Arterioscler Thromb Vasc Biol 15(11):1917–1927

    Article  PubMed  CAS  Google Scholar 

  114. Visioli F, Bernardini E (2011) Extra virgin olive oil's polyphenols: biological activities. Curr Pharm Des 17(8):786–804

    Article  PubMed  CAS  Google Scholar 

  115. Covas MI, Nyyssonen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, Gaddi A, de la Torre R, Mursu J, Baumler H, Nascetti S, Salonen JT, Fito M, Virtanen J, Marrugat J (2006) The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med 145(5):333–341

    PubMed  CAS  Google Scholar 

  116. Tangney CC, Scarmeas N (2012) The good, bad, and ugly? How blood nutrient concentrations may reflect cognitive performance. Neurology 78(4):230–231

    Article  PubMed  Google Scholar 

  117. Scarmeas N, Stern Y, Mayeux R, Luchsinger JA (2006) Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol

  118. Scarmeas N, Luchsinger JA, Schupf N, Brickman AM, Cosentino S, Tang MX, Stern Y (2009) Physical activity, diet, and risk of Alzheimer disease. Jama 302(6):627–637

    Article  PubMed  CAS  Google Scholar 

  119. Tangney CC, Kwasny MJ, Li H, Wilson RS, Evans DA, Morris MC (2011) Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am J Clin Nutr 93(3):601–607

    Article  PubMed  CAS  Google Scholar 

  120. Valls-Pedret C, Lamuela-Raventos RM, Medina-Remon A, Quintana M, Corella D, Pinto X, Martinez-Gonzalez MA, Estruch R, Ros E (2012) Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis 29(4):773–782

    PubMed  CAS  Google Scholar 

  121. Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alperovitch A (2007) Dietary patterns and risk of dementia: the Three-City cohort study. Neurology 69(20):1921–1930

    Article  PubMed  CAS  Google Scholar 

  122. Feart C, Samieri C, Rondeau V, Amieva H, Portet F, Dartigues JF, Scarmeas N, Barberger-Gateau P (2009) Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. Jama 302(6):638–648

    Article  PubMed  CAS  Google Scholar 

  123. Cherbuin N, Anstey KJ (2011) The mediterranean diet is not related to cognitive change in a large prospective investigation: the PATH through life study. Am J Geriatr Psychiatry. doi:10.1097/JGP.0b013e31823032a9

  124. Smith PJ, Blumenthal JA (2010) Diet and neurocognition: review of evidence and methodological considerations. Curr Aging Sci 3(1):57–66

    Article  PubMed  CAS  Google Scholar 

  125. Knopman DS (2009) Mediterranean diet and late-life cognitive impairment: a taste of benefit. Jama 302(6):686–687

    Article  PubMed  CAS  Google Scholar 

  126. Sofi F, Macchi C, Abbate R, Gensini GF, Casini A (2010) Effectiveness of the Mediterranean diet: can it help delay or prevent Alzheimer's disease? J Alzheimers Dis 20(3):795–801

    PubMed  Google Scholar 

  127. Wang L-S, Stoner GD (2008) Anthocyanins and their role in cancer prevention. Cancer Lett 269(2):281–290

    Article  PubMed  CAS  Google Scholar 

  128. Joseph JA, Shukitt-Hale B, Denisova NA, Prior RL, Cao G, Martin A, Taglialatela G, Bickford PC (1998) Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. J Neurosci 18(19):8047–8055

    PubMed  CAS  Google Scholar 

  129. Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, Bickford PC (1999) Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 19(18):8114–8121

    PubMed  CAS  Google Scholar 

  130. McGhie TK, Walton MC (2007) The bioavailability and absorption of anthocyanins: towards a better understanding. Mol Nutr Food Res 51(6):702–713

    Article  PubMed  CAS  Google Scholar 

  131. El Mohsen MA, Marks J, Kuhnle G, Moore K, Debnam E, Kaila Srai S, Rice-Evans C, Spencer JP (2006) Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats. Br J Nutr 95(1):51–58

    Article  PubMed  CAS  Google Scholar 

  132. Milbury PE, Kalt W (2010) Xenobiotic metabolism and berry flavonoid transport across the blood–brain barrier. J Agric Food Chem 58(7):3950–3956

    Article  PubMed  CAS  Google Scholar 

  133. Kalt W, Blumberg JB, McDonald JE, Vinqvist-Tymchuk MR, Fillmore SA, Graf BA, O'Leary JM, Milbury PE (2008) Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs. J Agric Food Chem 56(3):705–712

    Article  PubMed  CAS  Google Scholar 

  134. Goyarzu P, Malin DH, Lau FC, Taglialatela G, Moon WD, Jennings R, Moy E, Moy D, Lippold S, Shukitt-Hale B, Joseph JA (2004) Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci 7(2):75–83

    Article  PubMed  Google Scholar 

  135. Shan Q, Lu J, Zheng Y, Li J, Zhou Z, Hu B, Zhang Z, Fan S, Mao Z, Wang YJ, Ma D (2009) Purple sweet potato color ameliorates cognition deficits and attenuates oxidative damage and inflammation in aging mouse brain induced by d-galactose. J Biomed Biotechnol 2009:564737

    Article  PubMed  CAS  Google Scholar 

  136. Lu J, Wu DM, Zheng YL, Hu B, Zhang ZF (2010) Purple sweet potato color alleviates D-galactose-induced brain aging in old mice by promoting survival of neurons via PI3K pathway and inhibiting cytochrome C-mediated apoptosis. Brain Pathol 20(3):598–612

    Article  PubMed  CAS  Google Scholar 

  137. Shin W-H, Park S-J, Kim E-J (2006) Protective effect of anthocyanins in middle cerebral artery occlusion and reperfusion model of cerebral ischemia in rats. Life Sci 79(2):130–137

    Article  PubMed  CAS  Google Scholar 

  138. Min J, Yu S-W, Baek S-H, Nair KM, Bae O-N, Bhatt A, Kassab M, Nair MG, Majid A (2011) Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia. Neurosci Lett 500(3):157–161

    Article  PubMed  CAS  Google Scholar 

  139. Lu J, D-m Wu, Zheng Y-l HuB, Cheng W, Z-f Z (2012) Purple sweet potato color attenuates domoic acid-induced cognitive deficits by promoting estrogen receptor-α−mediated mitochondrial biogenesis signaling in mice. Free Radic Biol Med 52(3):646–659

    Article  PubMed  CAS  Google Scholar 

  140. Barros D, Amaral OB, Izquierdo I, Geracitano L, do Carmo Bassols Raseira M, Henriques AT, Ramirez MR (2006) Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacol Biochem Behav 84(2):229–234

  141. Casadesus G, Shukitt-Hale B, Stellwagen HM, Zhu X, Lee H-G, Smith MA, Joseph JA (2004) Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci 7(5–6):309–316

    Article  PubMed  CAS  Google Scholar 

  142. Valente T, Hidalgo J, Bolea I, Ramirez B, Angles N, Reguant J, Morello JR, Gutierrez C, Boada M, Unzeta M (2009) A diet enriched in polyphenols and polyunsaturated fatty acids, LMN diet, induces neurogenesis in the subventricular zone and hippocampus of adult mouse brain. J Alzheimers Dis 18(4):849–865

    PubMed  CAS  Google Scholar 

  143. Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B, Morgan D (2003) Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci 6(3):153–162

    Article  PubMed  CAS  Google Scholar 

  144. Hartman RE, Shah A, Fagan AM, Schwetye KE, Parsadanian M, Schulman RN, Finn MB, Holtzman DM (2006) Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease. Neurobiol Dis 24(3):506–515

    Article  PubMed  CAS  Google Scholar 

  145. Shih P-H, Chan Y-C, Liao J-W, Wang M-F, Yen G-C (2010) Antioxidant and cognitive promotion effects of anthocyanin-rich mulberry (Morus atropurpurea L.) on senescence-accelerated mice and prevention of Alzheimer's disease. J Nutr Biochem 21(7):598–605

    Article  PubMed  CAS  Google Scholar 

  146. Shukitt-Hale B, Carey AN, Jenkins D, Rabin BM, Joseph JA (2007) Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Neurobiol Aging 28(8):1187–1194

    Article  PubMed  CAS  Google Scholar 

  147. Shukitt-Hale B, Carey A, Simon L, Mark DA, Joseph JA (2006) Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 22(3):295–302

    Article  PubMed  CAS  Google Scholar 

  148. Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B, Joseph JA (2010) Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr 103(5):730–734

    Article  PubMed  CAS  Google Scholar 

  149. Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA (2010) Blueberry supplementation improves memory in older adults. J Agric Food Chem 58(7):3996–4000

    Article  PubMed  CAS  Google Scholar 

  150. Krikorian R, Boespflug EL, Fleck DE, Stein AL, Wightman JD, Shidler MD, Sadat-Hossieny S (2012) Concord grape juice supplementation and neurocognitive function in human aging. J Agric Food Chem

  151. Ng TP, Feng L, Niti M, Kua EH, Yap KB (2008) Tea consumption and cognitive impairment and decline in older Chinese adults. Am J Clin Nutr 88(1):224–231

    PubMed  CAS  Google Scholar 

  152. Song J, Xu H, Liu F, Feng L (2012) Tea and cognitive health in late life: current evidence and future directions. J Nutr Health Aging 16(1):31–34

    Article  PubMed  CAS  Google Scholar 

  153. Chow HH, Hakim IA (2011) Pharmacokinetic and chemoprevention studies on tea in humans. Pharmacol Res 64(2):105–112

    PubMed  CAS  Google Scholar 

  154. Butterfield DA, Poon HF (2005) The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease. Exp Gerontol 40(10):774–783

    Article  PubMed  CAS  Google Scholar 

  155. Takeda T (2009) Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice. Neurochem Res 34(4):639–659

    Article  PubMed  CAS  Google Scholar 

  156. Chan YC, Hosoda K, Tsai CJ, Yamamoto S, Wang MF (2006) Favorable effects of tea on reducing the cognitive deficits and brain morphological changes in senescence-accelerated mice. J Nutr Sci Vitaminol (Tokyo) 52(4):266–273

    Article  CAS  Google Scholar 

  157. Unno K, Ishikawa Y, Takabayashi F, Sasaki T, Takamori N, Iguchi K, Hoshino M (2008) Daily ingestion of green tea catechins from adulthood suppressed brain dysfunction in aged mice. Biofactors 34(4):263–271

    Article  PubMed  Google Scholar 

  158. Unno K, Takabayashi F, Kishido T, Oku N (2004) Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10). Exp Gerontol 39(7):1027–1034

    Article  PubMed  CAS  Google Scholar 

  159. Unno K, Takabayashi F, Yoshida H, Choba D, Fukutomi R, Kikunaga N, Kishido T, Oku N, Hoshino M (2007) Daily consumption of green tea catechin delays memory regression in aged mice. Biogerontology 8(2):89–95

    Article  PubMed  CAS  Google Scholar 

  160. Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, Shytle RD, Tan J (2008) Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res

  161. Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, Oh KW, Hong JT (2009) Green tea (−)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. J Nutr 139(10):1987–1993

    Article  PubMed  CAS  Google Scholar 

  162. Assuncao M, Santos-Marques MJ, Carvalho F, Lukoyanov NV, Andrade JP (2011) Chronic green tea consumption prevents age-related changes in rat hippocampal formation. Neurobiol Aging 32(4):707–717

    Article  PubMed  CAS  Google Scholar 

  163. Haque AM, Hashimoto M, Katakura M, Hara Y, Shido O (2008) Green tea catechins prevent cognitive deficits caused by Abeta1-40 in rats. J Nutr Biochem 19(9):619–626

    Article  PubMed  CAS  Google Scholar 

  164. Halliwell B, Gutteridge J (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford

    Google Scholar 

  165. Hall AM, Roberson ED (2012) Mouse models of Alzheimer's disease. Brain Res Bull 88(1):3–12

    Google Scholar 

  166. Balducci C, Forloni G (2011) APP transgenic mice: their use and limitations. Neuromolecular Med 13(2):117–137

    Article  PubMed  CAS  Google Scholar 

  167. Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M (2010) Alzheimer's disease: clinical trials and drug development. Lancet Neurol 9(7):702–716

    Article  PubMed  CAS  Google Scholar 

  168. Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M (2009) Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis 16(1):85–91

    PubMed  CAS  Google Scholar 

  169. Qiu L, Sautter J, Gu D (2012) Associations between frequency of tea consumption and health and mortality: evidence from old Chinese. Br J Nutr:1–12

  170. Howes MJ, Perry NS, Houghton PJ (2003) Plants with traditional uses and activities, relevant to the management of Alzheimer's disease and other cognitive disorders. Phytother Res 17(1):1–18

    Article  PubMed  CAS  Google Scholar 

  171. Eckert GP (2010) Traditional used plants against cognitive decline and Alzheimer disease. Front Pharmacol 1:138

    Article  PubMed  Google Scholar 

  172. Ihl R, Tribanek M, Bachinskaya N (2012) Efficacy and tolerability of a once daily formulation of Ginkgo biloba extract EGb 761(R) in Alzheimer's disease and vascular dementia: results from a randomised controlled trial. Pharmacopsychiatry 45(2):41–46

    Google Scholar 

  173. Sastre J, Lloret A, Borras C, Pereda J, Garcia-Sala D, Droy-Lefaix MT, Pallardo FV, Vina J (2002) Ginkgo biloba extract EGb 761 protects against mitochondrial aging in the brain and in the liver. Cell Mol Biol (Noisy-le-grand) 48(6):685–692

    CAS  Google Scholar 

  174. Abdel-Kader RM, Hauptmann S, Keil U, Scherping I, Leuner K, Eckert A, Muller WE (2007) Stabilization of mitochondrial function by Ginkgo biloba extract (EGb 761). Pharmacol Res 56(6):493–502

    Article  PubMed  CAS  Google Scholar 

  175. Eckert GP, Renner K, Eckert SH, Eckmann J, Hagl S, Abdel-Kader RM, Kurz C, Leuner K, Muller WE (2012) Mitochondrial dysfunction-a pharmacological target in Alzheimer's disease. Mol Neurobiol. doi:10.1007/s12035-012-8271-z

  176. Bedir E, Tatli II, Khan RA, Zhao J, Takamatsu S, Walker LA, Goldman P, Khan IA (2002) Biologically active secondary metabolites from Ginkgo biloba. J Agric Food Chem 50(11):3150–3155

    Article  PubMed  CAS  Google Scholar 

  177. Fehske CJ, Leuner K, Muller WE (2009) Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment. Pharmacol Res Off J Ital Pharmacol Soc 60(1):68–73

    CAS  Google Scholar 

  178. Yoshitake T, Yoshitake S, Kehr J (2010) The Ginkgo biloba extract EGb 761(R) and its main constituent flavonoids and ginkgolides increase extracellular dopamine levels in the rat prefrontal cortex. Br J Pharmacol 159(3):659–668

    Article  PubMed  CAS  Google Scholar 

  179. Hou Y, Aboukhatwa MA, Lei DL, Manaye K, Khan I, Luo Y (2010) Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice. Neuropharmacology 58(6):911–920

    Article  PubMed  CAS  Google Scholar 

  180. Tchantchou F, Xu Y, Wu Y, Christen Y, Luo Y (2007) EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer's disease. FASEB J 21(10):2400–2408

    Article  PubMed  CAS  Google Scholar 

  181. Muller WE, Heiser J, Leuner K (2012) Effects of standardized Ginkgo biloba extract EGb 761 on neuroplasticity. Int Psychogeriatr (in press)

  182. Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN (2010) Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr 10:14

    Article  PubMed  Google Scholar 

  183. Wang BS, Wang H, Song YY, Qi H, Rong ZX, Zhang L, Chen HZ (2010) Effectiveness of standardized ginkgo biloba extract on cognitive symptoms of dementia with a six-month treatment: a bivariate random effect meta-analysis. Pharmacopsychiatry 43(3):86–91

    Article  PubMed  Google Scholar 

  184. Farr SA, Price TO, Dominguez LJ, Motisi A, Saiano F, Niehoff ML, Morley JE, Banks WA, Ercal N, Barbagallo M (2012) Extra virgin olive oil improves learning and memory in SAMP8 mice. J Alzheimer's Dis: JAD 28(1):81–92

    CAS  Google Scholar 

  185. Schaffer S, Podstawa M, Visioli F, Bogani P, Müller WE, Eckert GP (2007) Hydroxytyrosol-rich olive mill wastewater extract protects brain cells in vitro and ex vivo. J Agric Food Chem 55(13):5043–5049

    Article  PubMed  CAS  Google Scholar 

  186. Gonzalez-Correa JA, Navas MD, Lopez-Villodres JA, Trujillo M, Espartero JL, De La Cruz JP (2008) Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain slices subjected to hypoxia-reoxygenation. Neurosci Lett 446(2-3):143–146

    Google Scholar 

  187. Tuck KL, Freeman MP, Hayball PJ, Stretch GL, Stupans I (2001) The in vivo fate of hydroxytyrosol and tyrosol, antioxidant phenolic constituents of olive oil, after intravenous and oral dosing of labeled compounds to rats. J Nutr 131(7):1993–1996

    PubMed  CAS  Google Scholar 

  188. Covas MI, Miro-Casas E, Fito M, Farre-Albadalejo M, Gimeno E, Marrugat J, De La Torre R (2003) Bioavailability of tyrosol, an antioxidant phenolic compound present in wine and olive oil, in humans. Drugs Exp Clin Res 29(5–6):203–206

    PubMed  CAS  Google Scholar 

  189. Miro-Casas E, Covas MI, Farre M, Fito M, Ortuno J, Weinbrenner T, Roset P, de la Torre R (2003) Hydroxytyrosol disposition in humans. Clin Chem 49(6 Pt 1):945–952

    Article  PubMed  CAS  Google Scholar 

  190. Miro-Casas E, Covas MI, Fito M, Farre-Albadalejo M, Marrugat J, de la Torre R (2003) Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans. Eur J Clin Nutr 57(1):186–190

    Article  PubMed  CAS  Google Scholar 

  191. Visioli F, Romani A, Mulinacci N, Zarini S, Conte D, Vincieri FF, Galli C (1999) Antioxidant and other biological activities of olive mill waste waters. J Agric Food Chem 47(8):3397–3401

    Article  PubMed  CAS  Google Scholar 

  192. Bitler CM, Viale TM, Damaj B, Crea R (2005) Hydrolyzed olive vegetation water in mice has anti-inflammatory activity. J Nutr 135(6):1475–1479

    PubMed  CAS  Google Scholar 

  193. Capasso R, Sannino F, De Martino A, Manna C (2006) Production of triacetylhydroxytyrosol from olive mill waste waters for use as stabilized bioantioxidant. J Agric Food Chem 54(24):9063–9070

    Article  PubMed  CAS  Google Scholar 

  194. Liang BC, Miller L, Weller A (1999) Ethyl-nitrosourea transformed astrocytes exhibit mitochondrial membrane hyperpolarization and constrained apoptosis. Apoptosis 4(2):89–97

    Article  PubMed  CAS  Google Scholar 

  195. Southam CM, Ehrlich J (1943) Effects of extract of western red-cedar heartwood on certain wood-decaying fungi in culture. Phytopathology 33:517–524

    Google Scholar 

  196. Mattson MP, Cheng A (2006) Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses. Trends Neurosci 29(11):632–639

    Article  PubMed  CAS  Google Scholar 

  197. Cypser JR, Tedesco P, Johnson TE (2006) Hormesis and aging in Caenorhabditis elegans. Exp Gerontol 41(10):935–939

    Article  PubMed  CAS  Google Scholar 

  198. Saul N, Pietsch K, Sturzenbaum SR, Menzel R, Steinberg CE (2011) Diversity of polyphenol action in Caenorhabditis elegans: between toxicity and longevity. J Nat Prod 74(8):1713–1720

    Article  PubMed  CAS  Google Scholar 

  199. Saul N, Pietsch K, Menzel R, Sturzenbaum SR, Steinberg CE (2009) Catechin induced longevity in C. elegans: from key regulator genes to disposable soma. Mech Ageing Dev 130(8):477–486

    Article  PubMed  CAS  Google Scholar 

  200. Shah ZA, Li RC, Ahmad AS, Kensler TW, Yamamoto M, Biswal S, Dore S (2010) The flavanol (−)-epicatechin prevents stroke damage through the Nrf2/HO1 pathway. J Cereb Blood Flow Metab 30(12):1951–1961

    Article  PubMed  CAS  Google Scholar 

  201. Nguyen T, Sherratt PJ, Pickett CB (2003) Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43:233–260

    Article  PubMed  CAS  Google Scholar 

  202. Calabrese V, Cornelius C, Stella AM, Calabrese EJ (2010) Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes. Neurochem Res 35(12):1880–1915

    Article  PubMed  CAS  Google Scholar 

  203. Dinkova-Kostova AT, Talalay P (2008) Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol Nutr Food Res 52(Suppl 1):S128–S138

    PubMed  Google Scholar 

  204. Satoh T, Harada N, Hosoya T, Tohyama K, Yamamoto M, Itoh K (2009) Keap1/Nrf2 system regulates neuronal survival as revealed through study of keap1 gene-knockout mice. Biochem Biophys Res Commun 380(2):298–302

    Article  PubMed  CAS  Google Scholar 

  205. Krejsa CM, Franklin CC, White CC, Ledbetter JA, Schieven GL, Kavanagh TJ (2010) Rapid activation of glutamate cysteine ligase following oxidative stress. J Biol Chem 285(21):16116–16124

    Article  PubMed  CAS  Google Scholar 

  206. McWalter GK, Higgins LG, McLellan LI, Henderson CJ, Song L, Thornalley PJ, Itoh K, Yamamoto M, Hayes JD (2004) Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. J Nutr 134(12 Suppl):3499S–3506S

    PubMed  CAS  Google Scholar 

  207. Pocernich CB, Butterfield DA (2012) Elevation of glutathione as a therapeutic strategy in Alzheimer disease. Biochim Biophys Acta 1822(5):625–630

    Article  PubMed  CAS  Google Scholar 

  208. Kulinsky VI, Kolesnichenko LS (2007) Mitochondrial glutathione. Biochemistry (Mosc) 72(7):698–701

    Article  CAS  Google Scholar 

  209. Wadey AL, Muyderman H, Kwek PT, Sims NR (2009) Mitochondrial glutathione uptake: characterization in isolated brain mitochondria and astrocytes in culture. J Neurochem 109(Suppl 1):101–108

    Article  PubMed  CAS  Google Scholar 

  210. Rivera F, Costa G, Abin A, Urbanavicius J, Arruti C, Casanova G, Dajas F (2008) Reduction of ischemic brain damage and increase of glutathione by a liposomal preparation of quercetin in permanent focal ischemia in rats. Neurotox Res 13(2):105–114

    Article  PubMed  CAS  Google Scholar 

  211. Rebrin I, Zicker S, Wedekind KJ, Paetau-Robinson I, Packer L, Sohal RS (2005) Effect of antioxidant-enriched diets on glutathione redox status in tissue homogenates and mitochondria of the senescence-accelerated mouse. Free Radic Biol Med 39(4):549–557

    Article  PubMed  CAS  Google Scholar 

  212. Shenvi SV, Smith E, Hagen TM (2012) Identification of age-specific Nrf2 binding to a novel antioxidant response element locus in the Gclc promoter: a compensatory means for the loss of glutathione synthetic capacity in the aging rat liver? Aging Cell 11(2):297–304

    Article  PubMed  CAS  Google Scholar 

  213. Arumugam TV, Gleichmann M, Tang SC, Mattson MP (2006) Hormesis/preconditioning mechanisms, the nervous system and aging. Ageing Res Rev 5(2):165–178

    Article  PubMed  CAS  Google Scholar 

  214. Tapia PC (2006) Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: "Mitohormesis" for health and vitality. Med Hypotheses 66(4):832–843

    Article  PubMed  CAS  Google Scholar 

  215. Biasutto L, Szabo I, Zoratti M (2011) Mitochondrial effects of plant-made compounds. Antioxid Redox Signal 15(12):3039–3059

    Article  PubMed  CAS  Google Scholar 

  216. Vina J, Gomez-Cabrera MC, Borras C, Froio T, Sanchis-Gomar F, Martinez-Bello VE, Pallardo FV (2009) Mitochondrial biogenesis in exercise and in ageing. Adv Drug Deliv Rev 61(14):1369–1374

    Article  PubMed  CAS  Google Scholar 

  217. Davis JM, Murphy EA, Carmichael MD, Davis B (2009) Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol 296(4):R1071–R1077

    Article  PubMed  CAS  Google Scholar 

  218. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127(6):1109–1122

    Article  PubMed  CAS  Google Scholar 

  219. Cipolla MJ, Crete R, Vitullo L, Rix RD (2004) Transcellular transport as a mechanism of blood–brain barrier disruption during stroke. Front Biosci 9:777–785

    Article  PubMed  CAS  Google Scholar 

  220. Spear LP, Varlinskaya EI (2005) Low dose effects in psychopharmacology: ontogenetic considerations. Nonlinearity Biol Toxicol Med 3(1):97–111

    Article  PubMed  CAS  Google Scholar 

  221. Gruber J, Tang SY, Halliwell B (2007) Evidence for a trade-off between survival and fitness caused by resveratrol treatment of Caenorhabditis elegans. Ann N Y Acad Sci 1100:530–542

    Article  PubMed  CAS  Google Scholar 

  222. Cook RR, Calabrese EJ (2006) Hormesis is biology, not religion. Environ Health Perspect 114(12):A688

    Article  PubMed  Google Scholar 

  223. Cook R, Calabrese EJ (2006) The importance of hormesis to public health. Environ Health Perspect 114(11):1631–1635

    PubMed  CAS  Google Scholar 

  224. Halliwell B (2012) The antioxidant paradox: less paradoxical now? Br J Clin. Pharmacol doi:10.1111/j.1365-2125.2012.04272.x

  225. Lock K, Pomerleau J, Causer L, Altmann DR, McKee M (2005) The global burden of disease attributable to low consumption of fruit and vegetables: implications for the global strategy on diet. Bull World Health Organ 83(2):100–108

    PubMed  Google Scholar 

  226. Vitaglione P, Donnarumma G, Napolitano A, Galvano F, Gallo A, Scalfi L, Fogliano V (2007) Protocatechuic acid is the major human metabolite of cyanidin-glucosides. J Nutr 137(9):2043–2048

    PubMed  CAS  Google Scholar 

  227. Tsuda T, Horio F, Osawa T (1999) Absorption and metabolism of cyanidin 3-O-β−D-glucoside in rats. FEBS Lett 449(2-3):179–182

    Article  PubMed  CAS  Google Scholar 

  228. Guan S, Jiang B, Bao YM, An LJ (2006) Protocatechuic acid suppresses MPP+ −induced mitochondrial dysfunction and apoptotic cell death in PC12 cells. Food Chem Toxicol 44(10):1659–1666

    Article  PubMed  CAS  Google Scholar 

  229. Liu YM, Jiang B, Bao YM, An LJ (2008) Protocatechuic acid inhibits apoptosis by mitochondrial dysfunction in rotenone-induced PC12 cells. Toxicol In Vitro 22(2):430–437

    Article  PubMed  CAS  Google Scholar 

  230. Traka MH, Mithen RF (2011) Plant science and human nutrition: challenges in assessing health-promoting properties of phytochemicals. Plant Cell 23(7):2483–2497

    Article  PubMed  CAS  Google Scholar 

  231. Kidd PM (2009) Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts. Altern Med Rev 14(3):226–246

    PubMed  Google Scholar 

  232. Oidtmann J, Schantz M, Mader K, Baum M, Berg S, Betz M, Kulozik U, Leick S, Rehage H, Schwarz K, Richling E (2012) Preparation and comparative release characteristics of three anthocyanin encapsulation systems. J Agric Food Chem 60(3):844–851

    Article  PubMed  CAS  Google Scholar 

  233. Scheepens A, Tan K, Paxton JW (2010) Improving the oral bioavailability of beneficial polyphenols through designed synergies. Genes Nutr 5(1):75–87

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Centre for Life Sciences, National University of Singapore, 22 Medical Drive, Singapore, 117456, Singapore

    Sebastian Schaffer

  2. Institute of Nutritional Sciences, University of Giessen, 35392, Giessen, Germany

    Heike Asseburg & Sabine Kuntz

  3. Department of Pharmacology, Biocenter, Campus Riedberg, Goethe University, Biocentre Geb. N260, R.1.09, Max-von-Laue Str. 9, 60438, Frankfurt, Germany

    Heike Asseburg, Walter E. Muller & Gunter P. Eckert

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  1. Sebastian Schaffer
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  2. Heike Asseburg
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  3. Sabine Kuntz
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  4. Walter E. Muller
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  5. Gunter P. Eckert
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Correspondence to Gunter P. Eckert.

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Schaffer, S., Asseburg, H., Kuntz, S. et al. Effects of Polyphenols on Brain Ageing and Alzheimer’s Disease: Focus on Mitochondria. Mol Neurobiol 46, 161–178 (2012). https://doi.org/10.1007/s12035-012-8282-9

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  • DOI: https://doi.org/10.1007/s12035-012-8282-9

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