Skip to main content
×
Home
    • 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)
Abstract

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 no-reply@cambridge.org 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 @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ 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
      ×
Copyright
Corresponding author
*Corresponding author: Dr Jeremy P. E. Spencer, fax +44 118 931 0080, email j.p.e.spencer@reading.ac.uk
References
Hide All
1.Youdim KA & Joseph JA (2001) A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med 30, 583594.
2.Youdim KA, Spencer JPE, Schroeter H & Rice-Evans C (2002) Dietary flavonoids as potential neuroprotectants. Biol Chem 383, 503519.
3.Galli RL, Shukitt-Hale B, Youdim KA & Joseph JA (2002) Fruit polyphenolics and brain aging: nutritional interventions targeting age-related neuronal and behavioral deficits. Ann NY Acad Sci 959, 128132.
4.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, 10271034.
5.Haque AM, Hashimoto M, Katakura M, Tanabe Y, Hara Y & Shido O (2006) Long-term administration of green tea catechins improves spatial cognition learning ability in rats. J Nutr 136, 10431047.
6.Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H & Tsuji I (2006) Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr 83, 355361.
7.Wang Y, Wang L, Wu J & Cai J (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.Inanami O, Watanabe Y, Syuto B, Nakano M, Tsuji M & Kuwabara M (1998) Oral administration of (-)catechin protects against ischemia-reperfusion-induced neuronal death in the gerbil. Free Radic Res 29, 359365.
9.Luo Y, Smith JV, Paramasivam V, Burdick A, Curry KJ, Buford JP, Khan I, Netzer WJ, Xu H & Butko P (2002) Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci USA 99, 1219712202.
10.Bastianetto S, Zheng WH & Quirion R (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.
11.Zimmermann M, Colciaghi F, Cattabeni F & Di Luca M (2002) Ginkgo biloba extract: from molecular mechanisms to the treatment of Alzheimer's disease. Cell Mol Biol (Noisy-le-grand) 48, 613623.
12.Datla KP, Christidou M, Widmer WW, Rooprai HK & Dexter DT (2001) Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease. Neuroreport 12, 38713875.
13.Rice-Evans CA, Miller NJ & Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20, 933956.
14.Pollard SE, Kuhnle GG, Vauzour D, Vafeiadou K, Tzounis X, Whiteman M, Rice-Evans C & Spencer JPE (2006) The reaction of flavonoid metabolites with peroxynitrite. Biochem Biophys Res Commun 350, 960968.
15.Williams RJ, Spencer JPE & Rice-Evans C (2004) Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36, 838849.
16.Spencer JPE, Rice-Evans C & Williams RJ (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.Schroeter H, Boyd C, Spencer JPE, Williams RJ, Cadenas E & Rice-Evans C (2002) MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Neurobiol Aging 23, 861880.
18.Manach C, Scalbert A, Morand C, Remesy C & Jimenez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79, 727747.
19.Rice-Evans C (2001) Flavonoid antioxidants. Curr Med Chem 8, 797807.
20.Rice-Evans C (1995) Plant polyphenols: free radical scavengers or chain-breaking antioxidants? Biochem Soc Symp 61, 103116.
21.Spencer JPE, Schroeter H, Rechner AR & Rice-Evans C (2001) Bioavailability of flavan-3-ols and procyanidins: gastrointestinal tract influences and their relevance to bioactive forms in vivo. Antioxid Redox Signal 3, 10231039.
22.Spencer JPE, Abd El Mohsen MM, Minihane AM & Mathers JC (2007) Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research. Br J Nutr 111.
23.Spencer JPE, Chowrimootoo G, Choudhury R, Debnam ES, Srai SK & Rice-Evans C (1999) The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett 458, 224230.
24.Spencer JPE (2003) Metabolism of tea flavonoids in the gastrointestinal tract. J Nutr 133, 3255S3261S.
25.Scheline RR (1999) Metabolism of oxygen heterocyclic compounds. CRC Handbook of Mammalian Metabolism of Plant Compounds, pp. 243295 Boca Raton, FL: CRC Press Inc.
26.Spencer JPE, Kuhnle GG, Williams RJ & Rice-Evans C (2003) Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem J 372, 173181.
27.Spencer JPE, Schroeter H, Crossthwaithe AJ, Kuhnle G, Williams RJ & Rice-Evans C (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.Miyake Y, Shimoi K, Kumazawa S, Yamamoto K, Kinae N & Osawa T (2000) Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats. J Agric Food Chem 48, 32173224.
29.Terao J, Yamaguchi S, Shirai M, Miyoshi M, Moon JH, Oshima S, Inakuma T, Tsushida T & Kato Y (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.Shirai M, Moon JH, Tsushida T & Terao J (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.Yamamoto N, Moon JH, Tsushida T, Nagao A & Terao J (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.da Silva EL, Piskula MK, Yamamoto N, Moon JH & Terao J (1998) Quercetin metabolites inhibit copper ion-induced lipid peroxidation in rat plasma. FEBS Lett 430, 405408.
33.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, 13641371.
34.Ho SC, Chan AS, Ho YP, So EK, Sham A, Zee B & Woo JL (2007) Effects of soy isoflavone supplementation on cognitive function in Chinese postmenopausal women: a double-blind, randomized, controlled trial. Menopause 14, 489499.
35.Lee YB, Lee HJ & Sohn HS (2005) Soy isoflavones and cognitive function. J Nutr Biochem 16, 641649.
36.File SE, Jarrett N, Fluck E, Duffy R, Casey K & Wiseman H (2001) Eating soya improves human memory. Psychopharmacology (Berl) 157, 430436.
37.Kim H, Xia H, Li L & Gewin J (2000) Attenuation of neurodegeneration-relevant modifications of brain proteins by dietary soy. Biofactors 12, 243250.
38.Birge SJ (1996) Is there a role for estrogen replacement therapy in the prevention and treatment of dementia? J Am Geriatr Soc 44, 865870.
39.Henderson VW (2006) Estrogen-containing hormone therapy and Alzheimer's disease risk: understanding discrepant inferences from observational and experimental research. Neuroscience 138, 10311039.
40.Casini ML, Marelli G, Papaleo E, Ferrari A, D'Ambrosio F & Unfer V (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.Kritz-Silverstein D, Von Mühlen D, Barrett-Connor E & Bressel MA (2003) Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study. Menopause 10, 196202.
42.File SE, Hartley DE, Elsabagh S, Duffy R & Wiseman H (2005) Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function. Menopause 12, 193201.
43.Zippel R, Balestrini M, Lomazzi M & Sturani E (2000) Calcium and calmodulin are essential for Ras-GRF1-mediated activation of the Ras pathway by lysophosphatidic acid. Exp Cell Res 258, 403408.
44.Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, Lampe JW & van der Schouw YT (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.
45.Fournier LR, Ryan Borchers TA, Robison LM, Wiediger M, Park JS, Chew BP, McGuire MK, Sclar DA, Skaer TL & Beerman KA (2007) The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women. J Nutr Health Aging 11, 155164.
46.Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A & van der Schouw YT (2007) Dietary phytoestrogen intake and cognitive function in older women. J Gerontol A Biol Sci Med Sci 62, 556562.
47.Barnes S, Boersma B, Patel R, Kirk M, Darley-Usmar VM, Kim H & Xu J (2000) Isoflavonoids and chronic disease: mechanisms of action. Biofactors 12, 209215.
48.Kim H, Peterson TG & Barnes S (1998) Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor beta signaling pathways. Am J Clin Nutr 68, 1418S1425S.
49.Schroeter H, Heiss C, Balzer J, Kleinbongard P, Keen CL, Hollenberg NK, Sies H, Kwik-Uribe C, Schmitz HH & Kelm M (2006) (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA 103, 10241029.
50.Francis ST, Head K, Morris PG & Macdonald IA (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.Fisher ND, Sorond FA & Hollenberg NK (2006) Cocoa flavanols and brain perfusion. J Cardiovasc Pharmacol 47, Suppl. 2, S210S214.
52.Dinges DF (2006) Cocoa flavanols, cerebral blood flow, cognition, and health: going forward. J Cardiovasc Pharmacol 47, Suppl. 2, S221S223.
53.Gage FH (2000) Mammalian neural stem cells. Science 287, 14331438.
54.Palmer TD, Willhoite AR & Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425, 479494.
55.Harris KM & Kater SB (1994) Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. Annu Rev Neurosci 17, 341371.
56.van Praag H, Lucero MJ, Yeo GW et al. (2007) Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci 27, 58695878.
57.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, 80478055.
58.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, 81148121.
59.Casadesus G, Shukitt-Hale B, Stellwagen HM, Zhu X, Lee HG, Smith MA & Joseph JA (2004) Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci 7, 309316.
60.Shukitt-Hale B, Smith DE, Meydani M & Joseph JA (1999) The effects of dietary antioxidants on psychomotor performance in aged mice. Exp Gerontol 34, 797808.
61.Joseph JA, Shukitt-Hale B & Casadesus G (2005) Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr 81, 313S316S.
62.Goyarzu P, Malin DH, Lau FC et al. (2004) Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci 7, 7583.
63.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, 153162.
64.Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM & Joseph JA (2005) Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 8, 111120.
65.Ramirez MR, Izquierdo I, do Carmo Bassols RM, Zuanazzi JA, Barros D & Henriques AT (2005) Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in adult rats. Pharmacol Res 52, 457462.
66.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, 266273.
67.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, 295302.
68.Singh A, Naidu PS & Kulkarni SK (2003) Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid. Free Radic Res 37, 12451252.
69.Patil CS, Singh VP, Satyanarayan PS, Jain NK, Singh A & Kulkarni SK (2003) Protective effect of flavonoids against aging- and lipopolysaccharide-induced cognitive impairment in mice. Pharmacology 69, 5967.
70.Wang H, Hu Y & Tsien JZ (2006) Molecular and systems mechanisms of memory consolidation and storage. Prog Neurobiol 79, 123135.
71.Squire LR & Zola-Morgan S (1991) The medial temporal lobe memory system. Science 253, 13801386.
72.Squire LR (2004) Memory systems of the brain: a brief history and current perspective. Neurobiol Learn Mem 82, 171177.
73.Squire LR, Stark CE & Clark RE (2004) The medial temporal lobe. Annu Rev Neurosci 27, 279306.
74.Alvarez P & Squire LR (1994) Memory consolidation and the medial temporal lobe: a simple network model. Proc Natl Acad Sci USA 91, 70417045.
75.Anagnostaras SG, Maren S & Fanselow MS (1999) Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination. J Neurosci 19, 11061114.
76.Zola-Morgan SM & Squire LR (1990) The primate hippocampal formation: evidence for a time-limited role in memory storage. Science 250, 288290.
77.Squire LR & Alvarez P (1995) Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr Opin Neurobiol 5, 169177.
78.Weeber EJ & Sweatt JD (2002) Molecular neurobiology of human cognition. Neuron 33, 845848.
79.Dash PK, Moore AN, Kobori N & Runyan JD (2007) Molecular activity underlying working memory. Learn Mem 14, 554563.
80.Tully T (1998) Toward a molecular biology of memory: the light's coming on! Nat Neurosci 1, 543545.
81.Carew TJ (1996) Molecular enhancement of memory formation. Neuron 16, 58.
82.Bramham CR & Wells DG (2007) Dendritic mRNA: transport, translation and function. Nat Rev Neurosci 8, 776789.
83.Martin KC, Barad M & Kandel ER (2000) Local protein synthesis and its role in synapse-specific plasticity. Curr Opin Neurobiol 10, 587592.
84.Kelleher RJ III, Govindarajan A & Tonegawa S (2004) Translational regulatory mechanisms in persistent forms of synaptic plasticity. Neuron 44, 5973.
85.Arnsten AF, Ramos BP, Birnbaum SG & Taylor JR (2005) Protein kinase A as a therapeutic target for memory disorders: rationale and challenges. Trends Mol Med 11, 121128.
86.van der Heide LP, Ramakers GM & Smidt MP (2006) Insulin signaling in the central nervous system: learning to survive. Prog Neurobiol 79, 205221.
87.Alkon DL, Sun MK & Nelson TJ (2007) PKC signaling deficits: a mechanistic hypothesis for the origins of Alzheimer's disease. Trends Pharmacol Sci 28, 5160.
88.Wei F, Qiu CS, Liauw J, Robinson DA, Ho N, Chatila T & Zhuo M (2002) Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat Neurosci 5, 573579.
89.Sweatt JD (2001) The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76, 110.
90.Sweatt JD (2004) Mitogen-activated protein kinases in synaptic plasticity and memory. Curr Opin Neurobiol 14, 311317.
91.Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS, Boss JM, McWeeney S, Dunn JJ, Mandel G & Goodman RH (2004) Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 119, 10411054.
92.Barco A, Bailey CH & Kandel ER (2006) Common molecular mechanisms in explicit and implicit memory. J Neurochem 97, 15201533.
93.Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G & Silva AJ (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 5968.
94.Tully T, Bourtchouladze R, Scott R & Tallman J (2003) Targeting the CREB pathway for memory enhancers. Nat Rev Drug Discov 2, 267277.
95.Pham TA, Impey S, Storm DR & Stryker MP (1999) CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period. Neuron 22, 6372.
96.Impey S, Smith DM, Obrietan K, Donahue R, Wade C & Storm DR (1998) Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat Neurosci 1, 595601.
97.Impey S, Mark M, Villacres EC, Poser S, Chavkin C & Storm DR (1996) Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus. Neuron 16, 973982.
98.Finkbeiner S (2000) CREB couples neurotrophin signals to survival messages. Neuron 25, 1114.
99.Finkbeiner S, Tavazoie SF, Maloratsky A, Jacobs KM, Harris KM & Greenberg ME (1997) CREB: a major mediator of neuronal neurotrophin responses. Neuron 19, 10311047.
100.Abbott NJ (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200, 629638.
101.Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ & Rice-Evans C (2003) Interaction between flavonoids and the blood-brain barrier: in vitro studies. J Neurochem 85, 180192.
102.Youdim KA, Shukitt-Hale B & Joseph JA (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.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 Radic Biol Med 36, 592604.
104.Aasmundstad TA, Morland J & Paulsen RE (1995) Distribution of morphine 6-glucuronide and morphine across the blood-brain barrier in awake, freely moving rats investigated by in vivo microdialysis sampling. J Pharmacol Exp Ther 275, 435441.
105.Sperker B, Backman JT & Kroemer HK (1997) The role of beta-glucuronidase in drug disposition and drug targeting in humans. Clin Pharmacokinet 33, 1831.
106.Kroemer HK & Klotz U (1992) Glucuronidation of drugs. A re-evaluation of the pharmacological significance of the conjugates and modulating factors. Clin Pharmacokinet 23, 292310.
107.Lin JH & Yamazaki M (2003) Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 42, 5998.
108.Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H & Fujiki H (1998) Wide distribution of [3H](-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 19, 17711776.
109.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, 16931702.
110.Talavera S, Felgines C, Texier O, Besson C, Gil-Izquierdo A, Lamaison JL & Remesy C (2005) Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. J Agric Food Chem 53, 39023908.
111.Abd El Mohsen MM, Marks J, Kuhnle G, Moore K, Debnam E, Kaila SS, Rice-Evans C & Spencer JPE (2006) Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats. Br J Nutr 95, 5158.
112.Halliwell B, Zhao K & Whiteman M (2000) The gastrointestinal tract: a major site of antioxidant action? Free Radic Res 33, 819830.
113.Vauzour D, Vafeiadou K, Corona G, Pollard SE, Tzounis X & Spencer JPE (2007) Champagne wine polyphenols protect primary cortical neurons against peroxynitrite-induced injury. J Agric Food Chem 55, 28542860.
114.Vafeiadou K, Vauzour D & Spencer JPE (2007) Neuroinflammation and its modulation by flavonoids. Endocr Metab Immune Disord Drug Targets 7, 211224.
115.Matter WF, Brown RF & Vlahos CJ (1992) The inhibition of phosphatidylinositol 3-kinase by quercetin and analogs. Biochem Biophys Res Commun 186, 624631.
116.Vlahos CJ, Matter WF, Hui KY & Brown RF (1994) A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem 269, 52415248.
117.Agullo G, Gamet-Payrastre L, Manenti S, Viala C, Remesy C, Chap H & Payrastre B (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.Gamet-Payrastre L, Manenti S, Gratacap MP, Tulliez J, Chap H & Payrastre B (1999) Flavonoids and the inhibition of PKC and PI 3-kinase. Gen Pharmacol 32, 279286.
119.Kong AN, Yu R, Chen C, Mandlekar S & Primiano T (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.Schroeter H, Spencer JPE, Rice-Evans C & Williams RJ (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.Spencer JPE (2007) The interactions of flavonoids within neuronal signalling pathways. Genes Nutr 2, 257273.
122.Conseil G, Baubichon-Cortay H, Dayan G, Jault JM, Barron D & Di Pietro A (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.Di Pietro A, Godinot C, Bouillant ML & Gautheron DC (1975) Pig heart mitochondrial ATPase: properties of purified and membrane-bound enzyme. Effects of flavonoids. Biochimie 57, 959967.
124.Barzilai A & Rahamimoff H (1983) Inhibition of Ca2+-transport ATPase from synaptosomal vesicles by flavonoids. Biochim Biophys Acta 730, 245254.
125.Revuelta MP, Cantabrana B & Hidalgo A (1997) Depolarization-dependent effect of flavonoids in rat uterine smooth muscle contraction elicited by CaCl2. Gen Pharmacol 29, 847857.
126.Lee SF & Lin JK (1997) Inhibitory effects of phytopolyphenols on TPA-induced transformation, PKC activation, and c-jun expression in mouse fibroblast cells. Nutr Cancer 28, 177183.
127.Ursini F, Maiorino M, Morazzoni P, Roveri A & Pifferi G (1994) A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation. Free Radic Biol Med 16, 547553.
128.Kantengwa S & Polla BS (1991) Flavonoids, but not protein kinase C inhibitors, prevent stress protein synthesis during erythrophagocytosis. Biochem Biophys Res Commun 180, 308314.
129.Rosenblat M, Belinky P, Vaya J, Levy R, Hayek T, Coleman R, Merchav S & Aviram M (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.
130.Boege F, Straub T, Kehr A, Boesenberg C, Christiansen K, Andersen A, Jakob F & Kohrle J (1996) Selected novel flavones inhibit the DNA binding or the DNA religation step of eukaryotic topoisomerase I. J Biol Chem 271, 22622270.
131.Medina JH, Viola H, Wolfman C, Marder M, Wasowski C, Calvo D & Paladini AC (1997) Overview – Flavonoids: a new family of benzodiazepine receptor ligands. Neurochem Res 22, 419425.
132.Dekermendjian K, Kahnberg P, Witt MR, Sterner O, Nielsen M & Liljefors T (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.Fischer PM & Lane DP (2000) Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics. Curr Med Chem 7, 12131245.
134.Huang YT, Hwang JJ, Lee PP, Ke FC, Huang JH, Huang CJ, Kandaswami C, Middleton E Jr & Lee MT (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.So FV, Guthrie N, Chambers AF, Moussa M & Carroll KK (1996) Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 26, 167181.
136.Green DR & Reed JC (1998) Mitochondria and apoptosis. Science 281, 13091312.
137.Tatton WG & Olanow CW (1999) Apoptosis in neurodegenerative diseases: the role of mitochondria. Biochim Biophys Acta 1410, 195213.
138.Goyal L (2001) Cell death inhibition: keeping caspases in check. Cell 104, 805808.
139.Srinivasula SM, Hegde R, Saleh A et al. (2001) A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410, 112116.
140.Schroeter H, Bahia P, Spencer JPE, Sheppard O, Rattray M, Rice-Evans C & Williams RJ (2007) (-)-Epicatechin stimulates ERK-dependent cyclic AMP response element activity and upregulates GLUR2 in cortical neurons. J Neurochem 101, 15961606.
141.Maher P, Akaishi T & Abe K (2006) Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proc Natl Acad Sci USA 103, 1656816573.
142.Vauzour D, Vafeiadou K, Rice-Evans C, Williams RJ & Spencer JPE (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.Levites Y, Amit T, Youdim MB & Mandel S (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.
144.Reznichenko L, Amit T, Youdim MB & Mandel S (2005) Green tea polyphenol (-)-epigallocatechin-3-gallate induces neurorescue of long-term serum-deprived PC12 cells and promotes neurite outgrowth. J Neurochem 93, 11571167.
145.Pollard SE, Whiteman M & Spencer JPE (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.Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP & Williams RL (2000) Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell 6, 909919.
147.Jacobson KA, Moro S, Manthey JA, West PL & Ji XD (2002) Interactions of flavones and other phytochemicals with adenosine receptors. Adv Exp Med Biol 505, 163171.
148.Johnston GA (2005) GABA(A) receptor channel pharmacology. Curr Pharm Des 11, 18671885.
149.Adachi N, Tomonaga S, Tachibana T, Denbow DM & Furuse M (2006) (-)-Epigallocatechin gallate attenuates acute stress responses through GABAergic system in the brain. Eur J Pharmacol 531, 171175.
150.Han YS, Bastianetto S, Dumont Y & Quirion R (2006) Specific plasma membrane binding sites for polyphenols, including resveratrol, in the rat brain. J Pharmacol Exp Ther 318, 238245.
151.Nifli AP, Bosson-Kouame A, Papadopoulou N, Kogia C, Kampa M, Castagnino C, Stournaras C, Vercauteren J & Castanas E (2005) Monomeric and oligomeric flavanols are agonists of membrane androgen receptors. Exp Cell Res 309, 329339.
152.Klinge CM, Blankenship KA, Risinger KE, Bhatnagar S, Noisin EL, Sumanasekera WK, Zhao L, Brey DM & Keynton RS (2005) Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. J Biol Chem 280, 74607468.
153.Conkright MD, Guzman E, Flechner L, Su AI, Hogenesch JB & Montminy M (2003) Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness. Mol Cell 11, 11011108.
154.Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ & Greenberg ME (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20, 709726.
155.Shieh PB, Hu SC, Bobb K, Timmusk T & Ghosh A (1998) Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20, 727740.
156.Bramham CR & Messaoudi E (2005) BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol 76, 99125.
157.Patterson SL, Grover LM, Schwartzkroin PA & Bothwell M (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.Thomas K & Davies A (2005) Neurotrophins: a ticket to ride for BDNF. Curr Biol 15, R262R264.
159.Peng S, Wuu J, Mufson EJ & Fahnestock M (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.Michalski B & Fahnestock M (2003) Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease. Brain Res Mol Brain Res 111, 148154.
161.Egan MF, Kojima M, Callicott JH et al. (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257269.
162.Linnarsson S, Bjorklund A & Ernfors P (1997) Learning deficit in BDNF mutant mice. Eur J Neurosci 9, 25812587.
163.Mu JS, Li WP, Yao ZB & Zhou XF (1999) Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats. Brain Res 835, 259265.
164.Minichiello L, Korte M, Wolfer D, Kuhn R, Unsicker K, Cestari V, Rossi-Arnaud C, Lipp HP, Bonhoeffer T & Klein R (1999) Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 24, 401414.
165.Wullschleger S, Loewith R & Hall MN (2006) TOR signaling in growth and metabolism. Cell 124, 471484.
166.Ferriola PC, Cody V & Middleton E Jr (1989) Protein kinase C inhibition by plant flavonoids. Kinetic mechanisms and structure-activity relationships. Biochem Pharmacol 38, 16171624.
167.Schratt GM, Nigh EA, Chen WG, Hu L & Greenberg ME (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.Yin Y, Edelman GM & Vanderklish PW (2002) The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes. Proc Natl Acad Sci USA 99, 23682373.
169.Waltereit R, Dammermann B, Wulff P, Scafidi J, Staubli U, Kauselmann G, Bundman M & Kuhl D (2001) Arg3.1/Arc mRNA induction by Ca2+ and cAMP requires protein kinase A and mitogen-activated protein kinase/extracellular regulated kinase activation. J Neurosci 21, 54845493.
170.Soule J, Messaoudi E & Bramham CR (2006) Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. Biochem Soc Trans 34, 600604.
171.Lyford GL, Yamagata K, Kaufmann WE, Barnes CA, Sanders LK, Copeland NG, Gilbert DJ, Jenkins NA, Lanahan AA & Worley PF (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.Reznichenko L, Amit T, Youdim MB & Mandel S (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? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 129
Total number of PDF views: 633 *
Loading metrics...

Abstract views

Total abstract views: 967 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st October 2017. This data will be updated every 24 hours.