Skip to main content
    • Aa
    • Aa

Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance: Symposium on ‘Diet and mental health’

  • Jeremy P. E. Spencer (a1)

Emerging evidence suggests that dietary-derived flavonoids have the potential to improve human memory and neuro-cognitive performance via their ability to protect vulnerable neurons, enhance existing neuronal function and stimulate neuronal regeneration. Long-term potentiation (LTP) is widely considered to be one of the major mechanisms underlying memory acquisition, consolidation and storage in the brain and is known to be controlled at the molecular level by the activation of a number of neuronal signalling pathways. These pathways include the phosphatidylinositol-3 kinase/protein kinase B/Akt (Akt), protein kinase C, protein kinase A, Ca–calmodulin kinase and mitogen-activated protein kinase pathways. Growing evidence suggests that flavonoids exert effects on LTP, and consequently memory and cognitive performance, through their interactions with these signalling pathways. Of particular interest is the ability of flavonoids to activate the extracellular signal-regulated kinase and the Akt signalling pathways leading to the activation of the cAMP-response element-binding protein, a transcription factor responsible for increasing the expression of a number of neurotrophins important in LTP and long-term memory. One such neurotrophin is brain-derived neurotrophic factor, which is known to be crucial in controlling synapse growth, in promoting an increase in dendritic spine density and in enhancing synaptic receptor density. The present review explores the potential of flavonoids and their metabolite forms to promote memory and learning through their interactions with neuronal signalling pathways pivotal in controlling LTP and memory in human subjects.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance
      Available formats
Corresponding author
*Corresponding author: Dr Jeremy P. E. Spencer, fax +44 118 931 0080, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1.KA Youdim & JA Joseph (2001) A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med 30, 583594.

2.KA Youdim , JPE Spencer , H Schroeter & C Rice-Evans (2002) Dietary flavonoids as potential neuroprotectants. Biol Chem 383, 503519.

3.RL Galli , B Shukitt-Hale , KA Youdim & JA Joseph (2002) Fruit polyphenolics and brain aging: nutritional interventions targeting age-related neuronal and behavioral deficits. Ann NY Acad Sci 959, 128132.

4.K Unno , F Takabayashi , T Kishido & N Oku (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, 10271034.

7.Y Wang , L Wang , J Wu & J Cai (2006) The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats. Br J Pharmacol 148, 147153.

8.O Inanami , Y Watanabe , B Syuto , M Nakano , M Tsuji & M Kuwabara (1998) Oral administration of (-)catechin protects against ischemia-reperfusion-induced neuronal death in the gerbil. Free Radic Res 29, 359365.

9.Y Luo , JV Smith , V Paramasivam , A Burdick , KJ Curry , JP Buford , I Khan , WJ Netzer , H Xu & P Butko (2002) Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci USA 99, 1219712202.

10.S Bastianetto , WH Zheng & R Quirion (2000) The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C. J Neurochem 74, 22682277.

12.KP Datla , M Christidou , WW Widmer , HK Rooprai & DT Dexter (2001) Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease. Neuroreport 12, 38713875.

13.CA Rice-Evans , NJ Miller & G Paganga (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20, 933956.

14.SE Pollard , GG Kuhnle , D Vauzour , K Vafeiadou , X Tzounis , M Whiteman , C Rice-Evans & JPE Spencer (2006) The reaction of flavonoid metabolites with peroxynitrite. Biochem Biophys Res Commun 350, 960968.

15.RJ Williams , JPE Spencer & C Rice-Evans (2004) Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36, 838849.

16.JPE Spencer , C Rice-Evans & RJ Williams (2003) Modulation of pro-survival Akt/PKB & ERK1/2 signalling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. J Biol Chem 278, 3478334793.

17.H Schroeter , C Boyd , JPE Spencer , RJ Williams , E Cadenas & C Rice-Evans (2002) MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Neurobiol Aging 23, 861880.

19.C Rice-Evans (2001) Flavonoid antioxidants. Curr Med Chem 8, 797807.

20.C Rice-Evans (1995) Plant polyphenols: free radical scavengers or chain-breaking antioxidants? Biochem Soc Symp 61, 103116.

21.JPE Spencer , H Schroeter , AR Rechner & C Rice-Evans (2001) Bioavailability of flavan-3-ols and procyanidins: gastrointestinal tract influences and their relevance to bioactive forms in vivo. Antioxid Redox Signal 3, 10231039.

23.JPE Spencer , G Chowrimootoo , R Choudhury , ES Debnam , SK Srai & C Rice-Evans (1999) The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett 458, 224230.

26.JPE Spencer , GG Kuhnle , RJ Williams & C Rice-Evans (2003) Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem J 372, 173181.

27.JPE Spencer , H Schroeter , AJ Crossthwaithe , G Kuhnle , RJ Williams & C Rice-Evans (2001) Contrasting influences of glucuronidation and O-methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts. Free Radic Biol Med 31, 11391146.

28.Y Miyake , K Shimoi , S Kumazawa , K Yamamoto , N Kinae & T Osawa (2000) Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats. J Agric Food Chem 48, 32173224.

29.J Terao , S Yamaguchi , M Shirai , M Miyoshi , JH Moon , S Oshima , T Inakuma , T Tsushida & Y Kato (2001) Protection by quercetin and quercetin 3-O-beta-D-glucuronide of peroxynitrite-induced antioxidant consumption in human plasma low-density lipoprotein. Free Radic Res 35, 925931.

30.M Shirai , JH Moon , T Tsushida & J Terao (2001) Inhibitory effect of a quercetin metabolite, quercetin 3-O-beta-D-glucuronide, on lipid peroxidation in liposomal membranes. J Agric Food Chem 49, 56025608.

31.N Yamamoto , JH Moon , T Tsushida , A Nagao & J Terao (1999) Inhibitory effect of quercetin metabolites and their related derivatives on copper ion-induced lipid peroxidation in human low-density lipoprotein. Arch Biochem Biophys 372, 347354.

32.EL da Silva , MK Piskula , N Yamamoto , JH Moon & J Terao (1998) Quercetin metabolites inhibit copper ion-induced lipid peroxidation in rat plasma. FEBS Lett 430, 405408.

33.L Letenneur , C Proust-Lima , A Le Gouge , JF Dartigues & P Barberger-Gateau (2007) Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 165, 13641371.

35.YB Lee , HJ Lee & HS Sohn (2005) Soy isoflavones and cognitive function. J Nutr Biochem 16, 641649.

36.SE File , N Jarrett , E Fluck , R Duffy , K Casey & H Wiseman (2001) Eating soya improves human memory. Psychopharmacology (Berl) 157, 430436.

37.H Kim , H Xia , L Li & J Gewin (2000) Attenuation of neurodegeneration-relevant modifications of brain proteins by dietary soy. Biofactors 12, 243250.

38.SJ Birge (1996) Is there a role for estrogen replacement therapy in the prevention and treatment of dementia? J Am Geriatr Soc 44, 865870.

39.VW Henderson (2006) Estrogen-containing hormone therapy and Alzheimer's disease risk: understanding discrepant inferences from observational and experimental research. Neuroscience 138, 10311039.

40.ML Casini , G Marelli , E Papaleo , A Ferrari , F D'Ambrosio & V Unfer (2006) Psychological assessment of the effects of treatment with phytoestrogens on postmenopausal women: a randomized, double-blind, crossover, placebo-controlled study. Fertil Steril 85, 972978.

41.D Kritz-Silverstein , Mühlen D Von , E Barrett-Connor & MA Bressel (2003) Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study. Menopause 10, 196202.

42.SE File , DE Hartley , S Elsabagh , R Duffy & H Wiseman (2005) Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function. Menopause 12, 193201.

43.R Zippel , M Balestrini , M Lomazzi & E Sturani (2000) Calcium and calmodulin are essential for Ras-GRF1-mediated activation of the Ras pathway by lysophosphatidic acid. Exp Cell Res 258, 403408.

44.S Kreijkamp-Kaspers , L Kok , DE Grobbee , EH de Haan , A Aleman , JW Lampe & YT van der Schouw (2004) Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA 292, 6574.

46.S Kreijkamp-Kaspers , L Kok , DE Grobbee , EH de Haan , A Aleman & YT van der Schouw (2007) Dietary phytoestrogen intake and cognitive function in older women. J Gerontol A Biol Sci Med Sci 62, 556562.

47.S Barnes , B Boersma , R Patel , M Kirk , VM Darley-Usmar , H Kim & J Xu (2000) Isoflavonoids and chronic disease: mechanisms of action. Biofactors 12, 209215.

49.H Schroeter , C Heiss , J Balzer , P Kleinbongard , CL Keen , NK Hollenberg , H Sies , C Kwik-Uribe , HH Schmitz & M Kelm (2006) (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA 103, 10241029.

50.ST Francis , K Head , PG Morris & IA Macdonald (2006) The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J Cardiovasc Pharmacol 47, Suppl. 2, S215S220.

51.ND Fisher , FA Sorond & NK Hollenberg (2006) Cocoa flavanols and brain perfusion. J Cardiovasc Pharmacol 47, Suppl. 2, S210S214.

52.DF Dinges (2006) Cocoa flavanols, cerebral blood flow, cognition, and health: going forward. J Cardiovasc Pharmacol 47, Suppl. 2, S221S223.

53.FH Gage (2000) Mammalian neural stem cells. Science 287, 14331438.

54.TD Palmer , AR Willhoite & FH Gage (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425, 479494.

55.KM Harris & SB Kater (1994) Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. Annu Rev Neurosci 17, 341371.

56.H van Praag , MJ Lucero , GW Yeo (2007) Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci 27, 58695878.

59.G Casadesus , B Shukitt-Hale , HM Stellwagen , X Zhu , HG Lee , MA Smith & JA Joseph (2004) Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci 7, 309316.

60.B Shukitt-Hale , DE Smith , M Meydani & JA Joseph (1999) The effects of dietary antioxidants on psychomotor performance in aged mice. Exp Gerontol 34, 797808.

62.P Goyarzu , DH Malin , FC Lau (2004) Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci 7, 7583.

63.JA Joseph , NA Denisova , G Arendash , M Gordon , D Diamond , B Shukitt-Hale & D Morgan (2003) Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci 6, 153162.

64.C Andres-Lacueva , B Shukitt-Hale , RL Galli , O Jauregui , RM Lamuela-Raventos & JA Joseph (2005) Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 8, 111120.

65.MR Ramirez , I Izquierdo , RM do Carmo Bassols , JA Zuanazzi , D Barros & AT Henriques (2005) Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in adult rats. Pharmacol Res 52, 457462.

66.YC Chan , K Hosoda , CJ Tsai , S Yamamoto & MF Wang (2006) Favorable effects of tea on reducing the cognitive deficits and brain morphological changes in senescence-accelerated mice. J Nutr Sci Vitaminol (Tokyo) 52, 266273.

67.B Shukitt-Hale , A Carey , L Simon , DA Mark & JA Joseph (2006) Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 22, 295302.

68.A Singh , PS Naidu & SK Kulkarni (2003) Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid. Free Radic Res 37, 12451252.

69.CS Patil , VP Singh , PS Satyanarayan , NK Jain , A Singh & SK Kulkarni (2003) Protective effect of flavonoids against aging- and lipopolysaccharide-induced cognitive impairment in mice. Pharmacology 69, 5967.

70.H Wang , Y Hu & JZ Tsien (2006) Molecular and systems mechanisms of memory consolidation and storage. Prog Neurobiol 79, 123135.

71.LR Squire & S Zola-Morgan (1991) The medial temporal lobe memory system. Science 253, 13801386.

72.LR Squire (2004) Memory systems of the brain: a brief history and current perspective. Neurobiol Learn Mem 82, 171177.

73.LR Squire , CE Stark & RE Clark (2004) The medial temporal lobe. Annu Rev Neurosci 27, 279306.

74.P Alvarez & LR Squire (1994) Memory consolidation and the medial temporal lobe: a simple network model. Proc Natl Acad Sci USA 91, 70417045.

76.SM Zola-Morgan & LR Squire (1990) The primate hippocampal formation: evidence for a time-limited role in memory storage. Science 250, 288290.

77.LR Squire & P Alvarez (1995) Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr Opin Neurobiol 5, 169177.

78.EJ Weeber & JD Sweatt (2002) Molecular neurobiology of human cognition. Neuron 33, 845848.

79.PK Dash , AN Moore , N Kobori & JD Runyan (2007) Molecular activity underlying working memory. Learn Mem 14, 554563.

80.T Tully (1998) Toward a molecular biology of memory: the light's coming on! Nat Neurosci 1, 543545.

81.TJ Carew (1996) Molecular enhancement of memory formation. Neuron 16, 58.

82.CR Bramham & DG Wells (2007) Dendritic mRNA: transport, translation and function. Nat Rev Neurosci 8, 776789.

83.KC Martin , M Barad & ER Kandel (2000) Local protein synthesis and its role in synapse-specific plasticity. Curr Opin Neurobiol 10, 587592.

84.RJ Kelleher III, A Govindarajan & S Tonegawa (2004) Translational regulatory mechanisms in persistent forms of synaptic plasticity. Neuron 44, 5973.

85.AF Arnsten , BP Ramos , SG Birnbaum & JR Taylor (2005) Protein kinase A as a therapeutic target for memory disorders: rationale and challenges. Trends Mol Med 11, 121128.

86.LP van der Heide , GM Ramakers & MP Smidt (2006) Insulin signaling in the central nervous system: learning to survive. Prog Neurobiol 79, 205221.

87.DL Alkon , MK Sun & TJ Nelson (2007) PKC signaling deficits: a mechanistic hypothesis for the origins of Alzheimer's disease. Trends Pharmacol Sci 28, 5160.

88.F Wei , CS Qiu , J Liauw , DA Robinson , N Ho , T Chatila & M Zhuo (2002) Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat Neurosci 5, 573579.

89.JD Sweatt (2001) The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76, 110.

90.JD Sweatt (2004) Mitogen-activated protein kinases in synaptic plasticity and memory. Curr Opin Neurobiol 14, 311317.

91.S Impey , SR McCorkle , H Cha-Molstad , JM Dwyer , GS Yochum , JM Boss , S McWeeney , JJ Dunn , G Mandel & RH Goodman (2004) Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 119, 10411054.

92.A Barco , CH Bailey & ER Kandel (2006) Common molecular mechanisms in explicit and implicit memory. J Neurochem 97, 15201533.

93.R Bourtchuladze , B Frenguelli , J Blendy , D Cioffi , G Schutz & AJ Silva (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 5968.

94.T Tully , R Bourtchouladze , R Scott & J Tallman (2003) Targeting the CREB pathway for memory enhancers. Nat Rev Drug Discov 2, 267277.

95.TA Pham , S Impey , DR Storm & MP Stryker (1999) CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period. Neuron 22, 6372.

96.S Impey , DM Smith , K Obrietan , R Donahue , C Wade & DR Storm (1998) Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat Neurosci 1, 595601.

97.S Impey , M Mark , EC Villacres , S Poser , C Chavkin & DR Storm (1996) Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus. Neuron 16, 973982.

98.S Finkbeiner (2000) CREB couples neurotrophin signals to survival messages. Neuron 25, 1114.

99.S Finkbeiner , SF Tavazoie , A Maloratsky , KM Jacobs , KM Harris & ME Greenberg (1997) CREB: a major mediator of neuronal neurotrophin responses. Neuron 19, 10311047.

100.NJ Abbott (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200, 629638.

101.KA Youdim , MS Dobbie , G Kuhnle , AR Proteggente , NJ Abbott & C Rice-Evans (2003) Interaction between flavonoids and the blood-brain barrier: in vitro studies. J Neurochem 85, 180192.

102.KA Youdim , B Shukitt-Hale & JA Joseph (2004) Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic Biol Med 37, 16831693.

103.KA Youdim , MZ Qaiser , DJ Begley , CA Rice-Evans & NJ Abbott (2004) Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med 36, 592604.

105.B Sperker , JT Backman & HK Kroemer (1997) The role of beta-glucuronidase in drug disposition and drug targeting in humans. Clin Pharmacokinet 33, 1831.

106.HK Kroemer & U Klotz (1992) Glucuronidation of drugs. A re-evaluation of the pharmacological significance of the conjugates and modulating factors. Clin Pharmacokinet 23, 292310.

107.JH Lin & M Yamazaki (2003) Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 42, 5998.

108.M Suganuma , S Okabe , M Oniyama , Y Tada , H Ito & H Fujiki (1998) Wide distribution of [3H](-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 19, 17711776.

109.MM Abd El Mohsen , G Kuhnle , AR Rechner , H Schroeter , S Rose , P Jenner & CA Rice-Evans (2002) Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic Biol Med 33, 16931702.

110.S Talavera , C Felgines , O Texier , C Besson , A Gil-Izquierdo , JL Lamaison & C Remesy (2005) Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. J Agric Food Chem 53, 39023908.

112.B Halliwell , K Zhao & M Whiteman (2000) The gastrointestinal tract: a major site of antioxidant action? Free Radic Res 33, 819830.

113.D Vauzour , K Vafeiadou , G Corona , SE Pollard , X Tzounis & JPE Spencer (2007) Champagne wine polyphenols protect primary cortical neurons against peroxynitrite-induced injury. J Agric Food Chem 55, 28542860.

114.K Vafeiadou , D Vauzour & JPE Spencer (2007) Neuroinflammation and its modulation by flavonoids. Endocr Metab Immune Disord Drug Targets 7, 211224.

115.WF Matter , RF Brown & CJ Vlahos (1992) The inhibition of phosphatidylinositol 3-kinase by quercetin and analogs. Biochem Biophys Res Commun 186, 624631.

117.G Agullo , L Gamet-Payrastre , S Manenti , C Viala , C Remesy , H Chap & B Payrastre (1997) Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition. Biochem Pharmacol 53, 16491657.

118.L Gamet-Payrastre , S Manenti , MP Gratacap , J Tulliez , H Chap & B Payrastre (1999) Flavonoids and the inhibition of PKC and PI 3-kinase. Gen Pharmacol 32, 279286.

119.AN Kong , R Yu , C Chen , S Mandlekar & T Primiano (2000) Signal transduction events elicited by natural products: role of MAPK and caspase pathways in homeostatic response and induction of apoptosis. Arch Pharm Res 23, 116.

120.H Schroeter , JPE Spencer , C Rice-Evans & RJ Williams (2001) Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochem J 358, 547557.

121.JPE Spencer (2007) The interactions of flavonoids within neuronal signalling pathways. Genes Nutr 2, 257273.

122.G Conseil , H Baubichon-Cortay , G Dayan , JM Jault , D Barron & A Di Pietro (1998) Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP- and steroid-binding sites on mouse P-glycoprotein. Proc Natl Acad Sci USA 95, 98319836.

123.A Di Pietro , C Godinot , ML Bouillant & DC Gautheron (1975) Pig heart mitochondrial ATPase: properties of purified and membrane-bound enzyme. Effects of flavonoids. Biochimie 57, 959967.

124.A Barzilai & H Rahamimoff (1983) Inhibition of Ca2+-transport ATPase from synaptosomal vesicles by flavonoids. Biochim Biophys Acta 730, 245254.

125.MP Revuelta , B Cantabrana & A Hidalgo (1997) Depolarization-dependent effect of flavonoids in rat uterine smooth muscle contraction elicited by CaCl2. Gen Pharmacol 29, 847857.

126.SF Lee & JK Lin (1997) Inhibitory effects of phytopolyphenols on TPA-induced transformation, PKC activation, and c-jun expression in mouse fibroblast cells. Nutr Cancer 28, 177183.

127.F Ursini , M Maiorino , P Morazzoni , A Roveri & G Pifferi (1994) A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation. Free Radic Biol Med 16, 547553.

128.S Kantengwa & BS Polla (1991) Flavonoids, but not protein kinase C inhibitors, prevent stress protein synthesis during erythrophagocytosis. Biochem Biophys Res Commun 180, 308314.

129.M Rosenblat , P Belinky , J Vaya , R Levy , T Hayek , R Coleman , S Merchav & M Aviram (1999) Macrophage enrichment with the isoflavan glabridin inhibits NADPH oxidase-induced cell-mediated oxidation of low density lipoprotein. A possible role for protein kinase C. J Biol Chem 274, 1379013799.

131.JH Medina , H Viola , C Wolfman , M Marder , C Wasowski , D Calvo & AC Paladini (1997) Overview – Flavonoids: a new family of benzodiazepine receptor ligands. Neurochem Res 22, 419425.

132.K Dekermendjian , P Kahnberg , MR Witt , O Sterner , M Nielsen & T Liljefors (1999) Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex. J Med Chem 42, 43434350.

133.PM Fischer & DP Lane (2000) Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics. Curr Med Chem 7, 12131245.

134.YT Huang , JJ Hwang , PP Lee , FC Ke , JH Huang , CJ Huang , C Kandaswami , E Middleton Jr & MT Lee (1999) Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br J Pharmacol 128, 9991010.

135.FV So , N Guthrie , AF Chambers , M Moussa & KK Carroll (1996) Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 26, 167181.

136.DR Green & JC Reed (1998) Mitochondria and apoptosis. Science 281, 13091312.

137.WG Tatton & CW Olanow (1999) Apoptosis in neurodegenerative diseases: the role of mitochondria. Biochim Biophys Acta 1410, 195213.

138.L Goyal (2001) Cell death inhibition: keeping caspases in check. Cell 104, 805808.

139.SM Srinivasula , R Hegde , A Saleh (2001) A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410, 112116.

140.H Schroeter , P Bahia , JPE Spencer , O Sheppard , M Rattray , C Rice-Evans & RJ Williams (2007) (-)-Epicatechin stimulates ERK-dependent cyclic AMP response element activity and upregulates GLUR2 in cortical neurons. J Neurochem 101, 15961606.

141.P Maher , T Akaishi & K Abe (2006) Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proc Natl Acad Sci USA 103, 1656816573.

142.D Vauzour , K Vafeiadou , C Rice-Evans , RJ Williams & JPE Spencer (2007) Activation of pro-survival Akt and ERK1/2 signaling pathways underlie the anti-apoptotic effects of flavanones in cortical neurons. J Neurochem 103, 13551367.

143.Y Levites , T Amit , MB Youdim & S Mandel (2002) Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action. J Biol Chem 277, 3057430580.

145.SE Pollard , M Whiteman & JPE Spencer (2006) Modulation of peroxynitrite-induced fibroblast injury by hesperetin: a role for intracellular scavenging and modulation of ERK signalling. Biochem Biophys Res Commun 347, 916923.

146.EH Walker , ME Pacold , O Perisic , L Stephens , PT Hawkins , MP Wymann & RL Williams (2000) Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell 6, 909919.

147.KA Jacobson , S Moro , JA Manthey , PL West & XD Ji (2002) Interactions of flavones and other phytochemicals with adenosine receptors. Adv Exp Med Biol 505, 163171.

148.GA Johnston (2005) GABA(A) receptor channel pharmacology. Curr Pharm Des 11, 18671885.

149.N Adachi , S Tomonaga , T Tachibana , DM Denbow & M Furuse (2006) (-)-Epigallocatechin gallate attenuates acute stress responses through GABAergic system in the brain. Eur J Pharmacol 531, 171175.

150.YS Han , S Bastianetto , Y Dumont & R Quirion (2006) Specific plasma membrane binding sites for polyphenols, including resveratrol, in the rat brain. J Pharmacol Exp Ther 318, 238245.

151.AP Nifli , A Bosson-Kouame , N Papadopoulou , C Kogia , M Kampa , C Castagnino , C Stournaras , J Vercauteren & E Castanas (2005) Monomeric and oligomeric flavanols are agonists of membrane androgen receptors. Exp Cell Res 309, 329339.

152.CM Klinge , KA Blankenship , KE Risinger , S Bhatnagar , EL Noisin , WK Sumanasekera , L Zhao , DM Brey & RS Keynton (2005) Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. J Biol Chem 280, 74607468.

153.MD Conkright , E Guzman , L Flechner , AI Su , JB Hogenesch & M Montminy (2003) Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness. Mol Cell 11, 11011108.

154.X Tao , S Finkbeiner , DB Arnold , AJ Shaywitz & ME Greenberg (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20, 709726.

155.PB Shieh , SC Hu , K Bobb , T Timmusk & A Ghosh (1998) Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20, 727740.

156.CR Bramham & E Messaoudi (2005) BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol 76, 99125.

157.SL Patterson , LM Grover , PA Schwartzkroin & M Bothwell (1992) Neurotrophin expression in rat hippocampal slices: a stimulus paradigm inducing LTP in CA1 evokes increases in BDNF & NT-3 mRNAs. Neuron 9, 10811088.

158.K Thomas & A Davies (2005) Neurotrophins: a ticket to ride for BDNF. Curr Biol 15, R262R264.

159.S Peng , J Wuu , EJ Mufson & M Fahnestock (2005) Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. J Neurochem 93, 14121421.

160.B Michalski & M Fahnestock (2003) Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease. Brain Res Mol Brain Res 111, 148154.

161.MF Egan , M Kojima , JH Callicott (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257269.

162.S Linnarsson , A Bjorklund & P Ernfors (1997) Learning deficit in BDNF mutant mice. Eur J Neurosci 9, 25812587.

163.JS Mu , WP Li , ZB Yao & XF Zhou (1999) Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats. Brain Res 835, 259265.

164.L Minichiello , M Korte , D Wolfer , R Kuhn , K Unsicker , V Cestari , C Rossi-Arnaud , HP Lipp , T Bonhoeffer & R Klein (1999) Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 24, 401414.

165.S Wullschleger , R Loewith & MN Hall (2006) TOR signaling in growth and metabolism. Cell 124, 471484.

166.PC Ferriola , V Cody & E Middleton Jr (1989) Protein kinase C inhibition by plant flavonoids. Kinetic mechanisms and structure-activity relationships. Biochem Pharmacol 38, 16171624.

167.GM Schratt , EA Nigh , WG Chen , L Hu & ME Greenberg (2004) BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development. J Neurosci 24, 73667377.

168.Y Yin , GM Edelman & PW Vanderklish (2002) The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes. Proc Natl Acad Sci USA 99, 23682373.

170.J Soule , E Messaoudi & CR Bramham (2006) Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. Biochem Soc Trans 34, 600604.

171.GL Lyford , K Yamagata , WE Kaufmann , CA Barnes , LK Sanders , NG Copeland , DJ Gilbert , NA Jenkins , AA Lanahan & PF Worley (1995) Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites. Neuron 14, 433445.

172.L Reznichenko , T Amit , MB Youdim & S Mandel (2005) Green tea polyphenol (-)-epigallocatechin-3-gallate induces neurorescue of long-term serum-deprived PC12 cells and promotes neurite outgrowth. J Neurochem 93, 11571167.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score