Beneficial Effects of Ginkgo biloba in Neurological Disorders

  • Akhlaq A. Farooqui


Ginkgo biloba (G. biloba), which belongs to the family Ginkgoaceae, is an important herb from the Chinese traditional system of medicine (Huh and Staba 1992). Extract prepared from its leaves has been used in traditional medicine for several hundred years. Major component of patented G. biloba leaves extract is called as EGb761. It was developed by Beaufour-Ipsen Pharma (Paris, France) and Dr. Willmar Schwabe Pharmaceuticals (Karlsruhe, Germany). EGb761 contains glycosides of the flavonols quercetin, isorhamnetin, and kaempferol (24 %); the terpene-lactones bilobalide and ginkgolides A, B and C, M, J, and bilobalide (6 %); and less than 5 ppm ginkgolic acid (Figs. 8.1 and 8.2) (Drieu 1986; DeFeudis and Drieu 2000). Other minor constituents of G. biloba include shikimic, vanillic, ascorbic, p-coumaric acids, steroids (sitosterol and stigmasterol), polyprenols, benzoic acid derivatives, carbohydrates, straight chain hydrocarbons, alcohol, ketones, and 2-hexenol. G. biloba constituents possess potent central nervous system (CNS) activity (Di Renzo 2000 including enhancement of memory, concentration, mental alertness, and decrease in mental fatigue. Many of these constituents produce memory boosting and mental altering effects, which are due to antioxidant- and neurogenesis-promoting properties of flavonols of G. biloba (Fig. 8.3) (Yoo et al. 2011). In addition, G. biloba terpenes are involved in antagonizing platelet activating factor, an endogenous mediator of inflammation and nociception produced by a variety of inflammatory cells, which may improve cardiovascular blood flow (Smith et al. 1996). G. biloba flavonoids have also been reported to dilate blood vessels by increasing the release of endothelium-derived relaxing factor and prostacyclin (PGI2) from vascular endothelial cells and decrease blood viscosity by antagonizing platelet activating factor.


Alzheimer Disease Huntington Disease Alzheimer Disease Patient Ginkgo Extract Ginkgo Biloba Extract 
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  1. Abdel-Kader R, Hauptmann S, Keil U, Scherping I, Leuner K, Eckert A (2007) Stabilization of mitochondrial function by Ginkgo biloba extract (EGb 761). Pharmacol Res 56:493–502PubMedGoogle Scholar
  2. Aderem A, Ulevitch RJ (2000) Toll-like receptors in the induction of the innate immune response. Nature 6797:782–787Google Scholar
  3. Ahlemeyer B, Krieglstein J (2003) Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci 60:1779–1792PubMedGoogle Scholar
  4. Amaral DG, Schumann CM, Wu NC (2008) Neuroanatomy of autism. Trends Neurosci 31:137–145PubMedGoogle Scholar
  5. Anderson KV (2000) Toll signaling pathways in the innate immune response. Curr Opin Immunol 12:13–19PubMedGoogle Scholar
  6. Ao Q, Sun XH, Wang AJ, Fu PF, Gong K, Zuo HC, Gong YD, Zhang XF (2006) Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after spinal cord injury in rats. Spinal Cord 44:662–667PubMedGoogle Scholar
  7. Arvanitis DN, Ducatenzeiler A, Ou JN, Grodstein E, Andrews SD, Tendulkar SR, Ribeiro-da-Silva A, Szyf M, Cuello AC (2007) High intracellular concentrations of amyloid-beta block nuclear translocation of phosphorylated CREB. J Neurochem 103:216–228PubMedGoogle Scholar
  8. Attella MJ, Hoffman SW, Stasio MJ, Stein DG (1989) Ginkgo biloba extract facilitates recovery from penetrating brain injury in adult male rats. Exp Neurol 105:62–71PubMedGoogle Scholar
  9. Augustin S, Rimbach G, Augustin K, Schliebs R, Wolffram S, Cermak R (2009) Effect of a short- and long-term treatment with Ginkgo biloba extract on amyloid precursor protein levels in a transgenic mouse model relevant to Alzheimer disease. Arch Biochem Biophys 481:177–182PubMedGoogle Scholar
  10. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495PubMedGoogle Scholar
  11. Bartus RT, Dean RI, Beer B, Lipppa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–417PubMedGoogle Scholar
  12. Bastianetto S, Ramassamy C, Dore S, Christen Y, Poirier J, Quirion R (2000) The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by betaamyloid. Eur J Neurosci 12:1882–1890PubMedGoogle Scholar
  13. Bate C, Salmona M, Williams A (2004) The role of platelet activating factor in prion and amyloid-beta neurotoxicity. Neuroreport 15:509–513PubMedGoogle Scholar
  14. Baudouin C, Ettaiche M, Fredj-Reygrobellet D, Droy-Lefaix MT, Gastaud P, Lapalus P (1992) Effects of gingko biloba extracts in a model of tractional retinal displacement. Lens Eye Toxic Res 9:513–519PubMedGoogle Scholar
  15. Bent S, Goldberg H, Padula A, Avins AL (2005) Spontaneous bleeding associated with Ginkgo biloba: a case report and systematic review of the literature: a case report and systematic review of the literature. J Gen Intern Med 20:657–661PubMedGoogle Scholar
  16. Biber A, Koch E (1999) Bioavailability of ginkgolides and bilobalide from extracts of Ginkgo biloba using GC/MS. Planta Med 65:192–193PubMedGoogle Scholar
  17. Biber A (2003) Pharmacokinetics of Ginkgo biloba extracts. Pharmacopsychiatry 36(Suppl 1):S32–S37PubMedGoogle Scholar
  18. Bidon C, Lachuer J, Molgó J, Wierinckx A, de la Porte S, Pignol B, Christen Y, Meloni R, Koenig H, Biguet NF, Jacques MJ (2009) The extract of Ginkgo biloba EGb 761 reactivates a juvenile profile in the skeletal muscle of sarcopenic rats by transcriptional reprogramming. PLoS One 4(11):e7998PubMedGoogle Scholar
  19. Birks J, Grimley Evan J (2009) Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev (1):CD003120Google Scholar
  20. Birkle DL, Kurian P, Braquet P, Bazan NG (1988) Platelet-activating factor antagonist BN52021 decreases accumulation of free polyunsaturated fatty acid in mouse brain during ischemia and electroconvulsive shock. J Neurochem 51:1900–1905PubMedGoogle Scholar
  21. Blecharz-Klin K, Oiechal A, Joniec I, Pyrzanowska J, Widy-Tysliewicz E (2009) Pharmacological and biochemical effects of Ginkgo biloba extract on learning, memory consolidation and motor activity in old rats. Acta Neurobiol Exp (Wars) 69:217–231Google Scholar
  22. Bolanos-Jimenez F, de Castro RM, Sarhan H, Prudhomme N, Drieu K, Fillion G (1995) Stress-induced 5-HT1A receptor desensitization: protective effects of Ginkgo biloba extract (EGb 761). Fundam Clin Pharmacol 9:169–174PubMedGoogle Scholar
  23. Braquet P (1988) Ginkgolides: chemistry, biology, pharmacology and clinical perspectives. J.R. Prous Science Publishers, Barcelona, SpainGoogle Scholar
  24. Chen C, Wei T-T, Gao Z, Zhao B-L, Hou J-W, Xu H-B (1999) Different effects of the constituents of Egb-761 on apoptosis in rat cerebellar granule cells induced by hydroxyl radicals. Biochem Mol Biol Int 47:397–405PubMedGoogle Scholar
  25. Chen JS, Huang PH, Wang CH, Lin FY, Tsai HY, Wu TC, Lin SJ, Chen JW (2011) Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract. Atherosclerosis 214:301–309PubMedGoogle Scholar
  26. Cho JH, Sung JH, Cho EH, Won CK, Lee HJ, Kim MO (2009) Gingko biloba Extract (EGb 761) prevents ischemic brain injury by activation of the Akt signaling pathway. Am J Chin Med 37:547–555PubMedGoogle Scholar
  27. Chopin P, Briley M (1992) Effects of four non-cholinergic cognitive enhancers in comparison with tacrine and galanthamine on scopolamine-induced amnesia in rats. Psychopharmacology (Berl) 106:26–30Google Scholar
  28. Chu X, Ci X, He J, Wei M, Yang X, Cao Q, Li H, Guan S, Deng Y, Pang D, Deng X (2011) A novel anti-inflammatory role for ginkgolide B in asthma via inhibition of the ERK/MAPK signaling pathway. Molecules 16:7634–7648PubMedGoogle Scholar
  29. Clostre F (1999) Ginkgo biloba extract (EGb 761). State of knowledge in the dawn of the year 2000. Ann Pharm Fr 57(Suppl 1):S8–S88Google Scholar
  30. Colciaghi F, Borroni B, Zimmermann M, Bellone C, Longhi A, Padovani A, Cattabene F, Christen Y, Di Luca M (2004) Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts. Neurobiol Dis 16:454–466PubMedGoogle Scholar
  31. DeFeudis FV (1991) Ginkgo biloba extract (EGb 761): pharmacological activities and clinical applications. Elsevier, Amsterdam, p 1187Google Scholar
  32. Defeudis FV (2002) Bilobalide and neuroprotection. Pharmacol Res 46:565–568PubMedGoogle Scholar
  33. DeFeudis FV, Drieu K (2000) Ginkgo biloba extract (EGb761) and CNS functions: basic studies and clinical applications. Curr Drug Targets 1:25–58PubMedGoogle Scholar
  34. Dinkova-Kostova AT, Holtzclaw WD, Kensler TW (2005) The role of Keap1 in cellular protective responses. Chem Res Toxicol 18:1779–1791PubMedGoogle Scholar
  35. Di Renzo G (2000) Ginkgo biloba and the central nervous system. Fitoterapia 71(Suppl 1):S43–S47PubMedGoogle Scholar
  36. Dorman DC, Cote LM, Buck WB (1992) Effects of an extract of gingko biloba on bromethalin-induced cerebral lipid peroxidation and edema in rats. Am J Vet Res 53:138–142PubMedGoogle Scholar
  37. Drieu K (1986) Preparation and definition of G. biloba extract. Presse Med 15:1455–1457PubMedGoogle Scholar
  38. Eckert A, Keil U, Kressmann S, Schindowski K, Leutner S, Leutz S, Muller WE (2003) Effects of EGb 761 Ginkgo biloba extract on mitochondrial function and oxidative stress. Pharmacopsychiatry 36(Suppl 1):S15–S23PubMedGoogle Scholar
  39. Edwards ER, Spira AP, Barnes DE, Yaffe K (2009) Neuropsychiatric symptoms in mild cognitive impairment: differences by subtype and progression to dementia. Int J Geriatr Psychiatry 24:716–722PubMedGoogle Scholar
  40. Fang W, Deng Y, Li Y, Shang E, Fang F, Lv P, Bai L, Qi Y, Yan F, Mao L (2010) Blood–brain barrier permeability and therapeutic time window of Ginkgolide B in ischemia-reperfusion injury. Eur J Pharm Sci 39:8–14PubMedGoogle Scholar
  41. Faraone SV, Biederman J (1998) Neurobiology of attention-deficit hyperactivity disorder. Biol Psychiatry 44:951–958PubMedGoogle Scholar
  42. Farooqui AA, Horrocks LA (2007) Glycerophospholipids in brain. Springer, New YorkGoogle Scholar
  43. Farooqui AA (2009) Hot topics in neural membrane lipidology. Springer, New YorkGoogle Scholar
  44. Farooqui AA (2010) Neurochemical aspects of neurotraumatic and neurodegenerative diseases. Springer, New YorkGoogle Scholar
  45. Farooqui AA (2012) Generation of reactive oxygen species in the brain: signaling for neural cell survival or suicide. In: Farooqui T, Farooqui AA (eds) Molecular aspects of oxidative stress on cell signaling in vertebrate and invertebrate. Wiley-Blackwell Publishers, Hoboken, pp 3–15Google Scholar
  46. Farooqui AA, Farooqui T, Panza F, Frisardi V (2012) Metabolic syndrome as a risk factor for neurological disorders. Cell Mol Life Sci 69(5):741–62PubMedGoogle Scholar
  47. Fong KC, Kinnear PE (2003) Retrobulbar haemorrhage associated with chronic Ginkgo biloba ingestion. Postgrad Med J 79:531–532PubMedGoogle Scholar
  48. Geda YE, Roberts RO, Knopman DS, Petersen RC, Christianson TJH, Pankratz VS, Smith GE, Boeve BF, Ivnik RJ, Tangalos EG, Rocca WA (2008) Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging. Arch Gen Psychiatry 65:1193–1198PubMedGoogle Scholar
  49. Goh LML, Barlow PJ (2004) Flavonoid recovery and stability from Ginkgo biloba subjected to a simulated digestion process. Food Chem 86:195–202Google Scholar
  50. Gohil K, Packer L (2002) Global gene expression analysis identifies cell and tissue specific actions of Ginkgo biloba extract, EGb 761. Cell Mol Biol 48:625–631PubMedGoogle Scholar
  51. Gunther EC, Strittmater SM (2010) beta-Amyloid oligomers and cellular prion protein in Alzheimer disease. J Mol Med (Berl) 88:331–338Google Scholar
  52. Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson disease: a target for neuroprotection? Lancet Neurol 8:382–397PubMedGoogle Scholar
  53. Holtzclaw WD, Dinkova-Kostova AT, Talalay P (2004) Protection against electrophile and oxidative stress by induction of phase 2 genes: the quest for the elusive sensor that responds to inducers. Adv Enzyme Regul 44:335–367PubMedGoogle Scholar
  54. Hoshino K, Kaisho T, Iwabe T, Takeuchi O, Akira S (2002) Differential involvement of IFN-β in Toll-like receptor-stimulated dendritic cell activation. Int Immunol 14:1225–1231PubMedGoogle Scholar
  55. 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 58:911–920PubMedGoogle Scholar
  56. Hoyer S, Lannert H, Nöldner M, Chatterjee SS (1999) Damaged neuronal energy metabolism and behavior are improved by Ginkgo biloba extract (EGb 761®). J Neural Transm 106:1171–1188PubMedGoogle Scholar
  57. Huang SH, Duke RK, Chebib M, Sasaki K, Wada K, Johnstob GA (2003) Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant α1β2γ2L GABAA receptors. Eur J Pharmacol 464:1–8PubMedGoogle Scholar
  58. Huguet F, Drieu K, Piriou A (1994) Decreased cerebral 5-HT1a receptors during ageing: reversal by Ginkgo biloba extract (EGb761). J Pharm Pharmacol 46:316–318PubMedGoogle Scholar
  59. Huh H, Staba EJ (1992) Botany and chemistry of Ginkgo biloba L. J Herbs Spices Med Plants 1:92–124Google Scholar
  60. Ihl R, Tribanek M, Bachinskaya N (2010) Baseline neuropsychiatric symptoms are effect modifiers in Ginkgo biloba extract (EGb 761®) treatment of dementia with neuropsychiatric features. Retrospective data analyses of a randomized controlled trial. J Neurol Sci 299:184–187PubMedGoogle Scholar
  61. Ivic L, Sands TT, Fishkin N, Nakanishi K, Kriegstein AR, Stromgaard K (2003) Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABAA receptors. J Biol Chem 278:49279–49285PubMedGoogle Scholar
  62. Jezova D, Duncko R, Lassanova M, Kriska M, Moncek F (2002) Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb 761®) in healthy volunteers. J Physiol Pharmacol 53:337–348PubMedGoogle Scholar
  63. Johannessen M, Delghandi MP, Moens U (2004) What turns CREB on? Cell Signal 16:1211–1227PubMedGoogle Scholar
  64. Karcher L, Zagerman P, Krieglstein J (1984) Effect of an extract of Ginkgo biloba on rat brain energy metabolism in hypoxia. Naunyn Schmiedebergs Arch Pharmacol 327:31–35PubMedGoogle Scholar
  65. Kiewert C, Kumar V, Hildmann O, Rueda M, Hartmann J, Naik RS, Klein J (2007) Role of GABAergic antagonism in the neuroprotective effects of bilobalide. Brain Res 1128:70–78PubMedGoogle Scholar
  66. Kiewert C, Kumar V, Hildmann O, Hartmann J, Hillert M, Klein J (2008) Role of glycine receptors and glycine release for the neuroprotective activity of bilobalide. Brain Res 1201:143–150PubMedGoogle Scholar
  67. Koch E (2005) Inhibition of platelet activating factor (PAF)-induced aggregation of human thrombocytes by ginkgolides: considerations on possible bleeding complications after oral intake of Ginkgo biloba extracts. Phytomedicine 12:10–16PubMedGoogle Scholar
  68. Koltermann A, Hartkorn A, Koch E, Fürst R, Vollmar AM, Zahler S (2007) Ginkgo biloba extract EGb 761 increases endothelial nitric oxide production in vitro and in vivo. Cell Mol Life Sci 64:1715–1722PubMedGoogle Scholar
  69. Költringer P, Langsteger W, Eber O (1995) Dose-dependent hemorheological effects and microcirculatory modifications following intravenous administration of Ginkgo biloba special extract EGb 761. Clin Hemorheol 15:649–656Google Scholar
  70. 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 23:1–16PubMedGoogle Scholar
  71. Krieglstein J, Beck T, Seibert A (1986) Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism. Life Sci 39:2327–2334PubMedGoogle Scholar
  72. Kristofiková Z and Klaschka J (1997) In vitro effect of Ginkgo biloba extract (EGb 761) on the activity of presynaptic cholinergic nerve terminals in rat hippocampus. Dement Geriatr Cogn Disord 8:43–48PubMedGoogle Scholar
  73. Kuchler-Bopp S, Dietrich J-B, Zaepfel M, Delaunoy J-P (2000) Receptor-mediated endocytosis of transthyretin by ependymoma cells. Brain Res 7:185–194Google Scholar
  74. Lacour M, Ez-Zaher L, Raymond J (1991) Plasticity mechanisms in vestibular compensation in the cat are improved by an extract of Ginkgo biloba (EGb 761). Pharmacol Biochem Behav 40:367–379PubMedGoogle Scholar
  75. Lang D, Ude C, Wurglics M, Schubert-Zsilavecz M, Klein J (2010) Brain permeability of bilobalide as probed by microdialysis before and after middle cerebral artery occlusion in mice. J Pharm Pharm Sci 13:607–614PubMedGoogle Scholar
  76. Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457:1128–1132PubMedGoogle Scholar
  77. Li Y, Peng H (2004) A study on suppressive effect of Ginkgo biloba extract on expressions of cell adhesion molecules induced by homocysteine. J Apoplexy Nerv Dis 21:332–334Google Scholar
  78. Li W, Trovero F, Cordier J, Wang Y, Drieu K, Papadopoulos V (2003) Prenatal exposure of rats to Ginkgo biloba extract (EGb 761) increases neuronal survival/growth and alters gene expression in the developing fetal hippocampus. Brain Res Dev Brain Res 144:169–180PubMedGoogle Scholar
  79. Liu XP, Goldring CEP, Copple IM, Wang HY, Wei W, Kitteringham NR, Park BK (2007) Extract of Ginkgo biloba induces phase 2 genes through keap1-NrF2-ARE signaling pathway. Life Sci 80:1586–1591PubMedGoogle Scholar
  80. Liu H, Dinkova-Kostova AT, Talalay P (2008a) Coordinate regulation of enzyme markers for inflammation and for protection against oxidants and electrophiles. Proc Natl Acad Sci USA 105:15926–15931PubMedGoogle Scholar
  81. Liu XP, Goldring CEP, Wang HY, Copple IM, Kitteringham NR, Park BK, Wei W (2008b) Extract of Ginkgo biloba induces glutamate cysteine ligase catalytic subunit (GCLC). Phytother Res 22:367–371PubMedGoogle Scholar
  82. Liu F, Zhang J, Yu S, Wang R, Wang B, Lai L, Yin H, Liu G (2008c) Inhibitory effect of Ginkgo Biloba extract on hyperhomocysteinemia-induced intimal thickening in rabbit abdominal aorta after balloon injury. Phytother Res 22:506–510PubMedGoogle Scholar
  83. Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM, Copeland JR, Dartigues JF, Jagger C, Martinez-Lage J, Soininen H, Hofman A (2000) Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 54(11 Suppl 5):S4–S9PubMedGoogle Scholar
  84. Loew D (2002) Value of Ginkgo biloba in treatment of Alzheimer dementia. Wien Med Wochenschr 152:418–422PubMedGoogle Scholar
  85. Longpre F, Garneau P, Christen Y, Ramassamy C (2006) Protection by EGb 761 against beta-amyloid-induced neurotoxicity: involvement of NF-kappaB, SIRT1, and MAPKs pathways and inhibition of amyloid fibril formation. Free Radic Biol Med 41:1781–1794PubMedGoogle Scholar
  86. Lu S, Guo X, Zhao P (2011) Effect of Ginkgo biloba extract 50 on immunity and antioxidant enzyme activities in ischemia reperfusion rats. Molecules 16:9194–9206PubMedGoogle Scholar
  87. Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JCS (2000) Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 157:708–714PubMedGoogle Scholar
  88. Ma Y, Hei A, Jin Y (1999) Beneficial effects of Ginkgo biloba injection on experimental focal cerebral ischemia in rats. J Cap Univ Med Sci 20:21–23Google Scholar
  89. Mahadevan S, Park Y (2008) Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses. J Food Sci 73:R14–R19PubMedGoogle Scholar
  90. Mahdy HM, Tadros MG, Mohamed MR, Karim AM, Khalifa AE (2011) The effect of Ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats. Neurochem Int 59:770–778PubMedGoogle Scholar
  91. Malinow MR, Nieto FJ, Szklo M, Chambless LE, Bond G (1993) Carotid artery intimal-medial wall thickening and plasma homocysteine in asymptomatic adults. The atherosclerosis risk in communities study. Circulation 87:1107–1113PubMedGoogle Scholar
  92. Martin SJ, Grimwood PD, Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711PubMedGoogle Scholar
  93. Mattson MP, Meffert MK (2006) Roles for NF-kappaB in nerve cell survival, plasticity, and disease. Cell Death Differ 13:852–860PubMedGoogle Scholar
  94. Mattson MP (2007) Mitochondrial regulation of neuronal plasticity. Neurochem Res 32:707–715PubMedGoogle Scholar
  95. Mattson MP, Gleichmann M, Cheng A (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60:748–766PubMedGoogle Scholar
  96. Mauri P, Minoggio M, Iemoli L, Rossoni G, Morazzoni P, Bombardelli E, Pietta P (2003) Liquidchromatography/atmospheric pressure chemical ionization ion trap mass spectrometry of terpene lactones in plasma of animals. J Pharm Biomed Anal 32:633–639PubMedGoogle Scholar
  97. Menkü A, Koç RK, Tayfur V, Saraymen R, Narin F, Akdemir H (2003) Effects of mexiletine, Ginkgo biloba extract (EGb 761), and their combination on experimental head injury. Neurosurg Rev 26:288–291PubMedGoogle Scholar
  98. Morita H, Kurihara H, Kuwaki T, Hamada C, Kitaoka M, Suzuki S (2000) Homocysteine as a risk factor for restenosis after coronary angioplasty. Thromb Haemost 84:27–31PubMedGoogle Scholar
  99. Morita H, Kurihara H, Yoshida S, Saito Y, Shindo T, Oh-hashi Y, Kurihara Y, Yazaki Y, Nagai R (2001) Diet-induced hyperhomocysteinemia exacerbates neointima formation in rat carotid arteries after balloon injury. Circulation 103:133–139PubMedGoogle Scholar
  100. Mössner R, Schmitt A, Syagailo Y, Gerlach M, Riederer P, Lesch KP (2000) The serotonin transporter in Alzheimer’s and Parkinson disease. J Neural Transm Suppl 60:345–350PubMedGoogle Scholar
  101. Naik SR, Pilgaonkar VW, Panda VS (2006) Evaluation of antioxidant activity of Ginkgo biloba phytosomes in rat brain. Phytother Res 20:1013–1016PubMedGoogle Scholar
  102. Nathan P (2000) Can the cognitive enhancing effects of Ginkgo biloba be explained by its pharmacology? Med Hypotheses 55:491–493PubMedGoogle Scholar
  103. Ni Y, Zhao B, Hou J, Xin W (1996) Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals. Neurosci Lett 214:115–118PubMedGoogle Scholar
  104. Niederhofer H (2009) First preliminary results of an observation of Ginkgo Biloba treating patients with autistic disorder. Phytother Res 23:1645–1646PubMedGoogle Scholar
  105. Niederhofer H (2010) Ginkgo biloba treating patients with attention-deficit disorder. Phytother Res 24:26–27PubMedGoogle Scholar
  106. Nishimura A, Ueda S, Takeuchi Y, Sawada T, Kawata M (1995) Age-related decrease of serotonergic fibres and S-100 beta immunoreactivity in the rat dentate gyrus. Neuroreport 6:1445–1448PubMedGoogle Scholar
  107. Numakawa T, Suzuki S, Kumamaru E, Adachi N, Richards M, Kunugi H (2010) BDNF function and intracellular signaling in neurons. Histol Histopathol 25:237–258PubMedGoogle Scholar
  108. Nygaard HB, Strittmatter SM (2009) Cellular prion protein mediates the toxicity of beta-amyloid oligomers: implications for Alzheimer disease. Arch Neurol 66:1325–1328PubMedGoogle Scholar
  109. Oken B, Storzbach D, Kaye J (1998) The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch Neurol 55:1409–1415PubMedGoogle Scholar
  110. Olanow CW, Tatton WG (1999) Etiology and pathogenesis of Parkinson disease. Annu Rev Neurosci 22:123–144PubMedGoogle Scholar
  111. Oliveira DR, Sanada PF, Saragossa Filho AC, Innocenti LR, Oler G, Cerutti JM, Cerutti SM (2009) Neuromodulatory property of standardized extract Ginkgo biloba L. (EGb 761) on memory: behavioral and molecular evidence. Brain Res 1269:68–89PubMedGoogle Scholar
  112. Palmen SJ, van Engeland H, Hof PR, Schmitz C (2004) Neuropathological findings in autism. Brain 127:2572–2583PubMedGoogle Scholar
  113. Park JW, Kwon HJ, Chung WS, Kim CY, Seong GJ (2011) Short-term effects of Ginkgo biloba extract on peripapillary retinal blood flow in normal tension glaucoma. Korean J Ophthalmol 25:323–328PubMedGoogle Scholar
  114. Peng H, Li Y-F, Sun S-G (2003) Effects of Ginkgo biloba extract on acute cerebral ischemia in rats analyzed by magnetic resonance spectroscopy. Acta Pharmacol Sin 24:467–471PubMedGoogle Scholar
  115. Pierre S, Jamme I, Droy-Lefaix M, Nouvelot A, Maixent J (1999) Ginkgo biloba extract (EGb 761) protects Na, K-ATPase activity during cerebral inschemia in mice. NeuroReport 10:47–51PubMedGoogle Scholar
  116. Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33:88–109PubMedGoogle Scholar
  117. Pittler MH, Ernst E (2000) Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med 108:276–281PubMedGoogle Scholar
  118. Polšek D, Jagatic T, Cepanec M, Hof PR, Simić G (2011) Recent developments in neuropathology of autism spectrum disorders. Transl Neurosci 2:256–264PubMedGoogle Scholar
  119. Porterfield SP (2000) Thyroidal dysfunction and environmental chemicals–potential impact on brain development. Environ Health Perspect 108:433–438PubMedGoogle Scholar
  120. Postina R (2008) A closer look at alpha-secretase. Curr Alzheimer Res 5:179–186PubMedGoogle Scholar
  121. Prusiner SB (2001) Shattuck lecture–neurodegenerative diseases and prions. N Engl J Med 344:1516–1526PubMedGoogle Scholar
  122. Przedborski S, Jackson-Lewis V, Djaldetti R, Liberatore G, Vila M, Vukosavic S, Almer G (2000) The parkinsonian toxin MPTP: action and mechanism. Restor Neurol Neurosci 16:135–142PubMedGoogle Scholar
  123. Rachidi W, Riondel J, McMahon HM, Favier A (2005) Prion protein and copper: a mysterious relationship. Pathol Biol (Paris) 53:244–250Google Scholar
  124. Ramassamy C, Christen Y, Clostre F, Costentin J (1992) The Ginkgo biloba extract, EGb761, increases synaptosomal uptake of 5-hydroxytptamine: in-vitro and ex-vitro studies. J Pharm Pharmacol 44:943–945PubMedGoogle Scholar
  125. Ramassamy C, Longpre F, Christen Y (2007) Ginkgo biloba extract (EGb 761) in Alzheimer disease: is there any evidence? Curr Alzheimer Res 4:253–262PubMedGoogle Scholar
  126. Rapin JR, Lamproglou I, Drieu K, Defeudis FV (1993) Demonstration of the “anti-stress” activity of an extract of Ginkgo biloba (EGb 761) using a discrimination learning task. Gen Pharmacol 25:1009–1016Google Scholar
  127. Rapport MD, Denney C, DuPaul GJ, Gardner MJ (1994) Attention deficit disorder and methylphenidate: normalization rates, clinical effectiveness, and response prediction in 76 patients. J Am Acad Child Adolesc Psychiatry 33:882–893PubMedGoogle Scholar
  128. Rendeiro C, Spencer JPE, Vauzour D, Butler LT, Ellis JA, Williams CM (2009) The impact of flavonoids on spatial memory in rodents: from behaviour to underlying hippocampal mechanisms. Genes Nutr 4:251–270PubMedGoogle Scholar
  129. Rhein V, Giese M, Baysang G, Meier F, Rao S, Schulz KL, Hamburger M, Eckert A (2010) Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure. PLoS One 5:e12359PubMedGoogle Scholar
  130. Rocher MN, Carré D, Spinnewyn B, Schulz J, Delaflotte S, Pignol B, Chabrier PE, Auguet M (2011) Long-term treatment with standardized Ginkgo biloba extract (EGb 761) attenuates cognitive deficits and hippocampal neuron loss in a gerbil model of vascular dementia. Fitoterapia 82:1075–1080PubMedGoogle Scholar
  131. Rojas P, Serrano-Garcia N, Mares-Samano JJ, Medina Campos ON, Pedraza J, Ogren SO (2008) EGb761 protects against nigrostriatal dopaminergic neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice: role of oxidative stress. Eur J Neurosci 28:41–50PubMedGoogle Scholar
  132. Rojas P, Serrano-García N, Medina-Campos ON, Pedraza-Chaverri J, Ogren SO, Rojas C (2011) Antidepressant-like effect of a Ginkgo biloba extract (EGb761) in the mouse forced swimming test: role of oxidative stress. Neurochem Int 59:628–636PubMedGoogle Scholar
  133. Rossi R, Basilico F, Rossoni G, Riva A, Morazzoni P, Mauri PL (2009) Liquid chromatography/atmospheric pressure chemical ionization ion trap mass spectrometry of bilobalide in plasma and brain of rats after oral administration of its phospholipidic complex. J Pharm Biomed Anal 50:224–227PubMedGoogle Scholar
  134. Ryu KH, Han HY, Lee SY, Jeon SD, Im GJ, Lee BY, Kim K, Lim KN, Chung JH (2009) Ginkgo biloba extract enhances antiplatelet and antithrombotic effects of cilostazol without prolongation of bleeding time. Thromb Res 124:328–334PubMedGoogle Scholar
  135. Saleem S, Zhuang H, Biswal S, Christen Y, Doré S (2008) Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury. Stroke 39:3389–3396PubMedGoogle Scholar
  136. Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A (2011) Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol 21:841–860PubMedGoogle Scholar
  137. Sasaki Y, Noguchi T, Yamamoto E, Giddings JC, Ikeda K, Yamori Y, Yamamoto J (2002) Effects of Ginkgo biloba extract (EGb 761) on cerebral thrombosis and blood pressure in stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 29:963–967PubMedGoogle Scholar
  138. Sastre J, Pallardo FV, de la Asuncion JG, Vina J (2000) Mitochondria, oxidative stress and aging. Free Radic Res 32:189–198PubMedGoogle Scholar
  139. Scoville WB, Milner B (2000) Loss of recent memory after bilateral hippocampal lesions. 1957. J Neuropsychiatry Clin Neurosci 12:103–113PubMedGoogle Scholar
  140. Shah ZA, Sharma P, Vohora SB (2003) Ginkgo biloba normalises stress-elevated alterations in brain catecholamines, serotonin and plasma corticosterone levels. Eur Neuropsychopharmacol 13:321–325PubMedGoogle Scholar
  141. Shi C, Zhao L, Zhu B, Li Q, Yew DT, Yao Z, Xu J (2009) Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against beta-amyloid peptideinduced toxicity in SH-SY5Y cells. Chem Biol Interact 181:115–123PubMedGoogle Scholar
  142. Shi C, Liu J, Wu F, Yew DT (2010) Ginkgo biloba extract in Alzheimer disease: from action mechanisms to medical practice. Int J Mol Sci 11:107–123PubMedGoogle Scholar
  143. Shi C, Zheng DD, Wu FM, Liu J, Xu J (2011) The phosphatidyl inositol 3 kinase-glycogen synthase kinase 3β pathway mediates bilobalide-induced reduction in amyloid β-peptide. Neurochem Res 37(2):298–306PubMedGoogle Scholar
  144. Singh N, Das D, Singh A, Mohan ML (2009) Prion protein and metal interaction: physiological and pathological implications. Curr Issues Mol Biol 12:99–108PubMedGoogle Scholar
  145. Smith PF, Maclennan K, Darlington CL (1996) The neuroprotective properties of the Ginkgo biloba leaf: a review of the possible relationship to platelet-activating factor (PAF). J Ethnopharmacol 50:131–139PubMedGoogle Scholar
  146. Smith J, Luo Y (2003) Elevation of oxidative free radicals in Alzheimer disease models can be attenuated by Ginkgo biloba extract EGb 761. J Alzheimers Dis 5:287–300PubMedGoogle Scholar
  147. Smith JV, Luo Y (2004) Studies on molecular mechanisms of Ginkgo biloba extract. Appl Microbiol Biotechnol 64:465–472PubMedGoogle Scholar
  148. Soule J, Messaoudi E, Bramham CR (2006) Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. Biochem Soc Trans 34:600–604PubMedGoogle Scholar
  149. Spencer JP, Rice-Evans C, Williams RJ (2003) Modulation of pro-survival Akt/Protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. J Biol Chem 278:34783–34793PubMedGoogle Scholar
  150. Squire LR, Zola-Morgan S (1991) The medial temporal lobe memory system. Science 253:1380–1386PubMedGoogle Scholar
  151. Steinberg M, Shao H, Zandi P, Lyketsos CG, Welsh-Bohmer KA, Norton MC, Breitner JC, Steffens DC, Tschanz JT, Investigators CC (2008) Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry 23:170–177PubMedGoogle Scholar
  152. Supattapone S (2004) Prion protein conversion in vitro. J Mol Med 82:348–356PubMedGoogle Scholar
  153. Tadano T, Nakagawasai O, Tan-no K, Morikawa Y, Takahashi N, Kisara K (1998) Effects of Ginkgo biloba extract on impairment of learning induced by cerebral ischemia in mice. Am J Chin Med 26:127–132PubMedGoogle Scholar
  154. Taylor JE (1986) Neuromediator binding to receptors in the rat brain. The effect of chronic administration of Ginkgo biloba extract. Presse Med 15:491–493Google Scholar
  155. 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 disease. FASEB J 21:2400–2408PubMedGoogle Scholar
  156. Tendi EA, Bosetti F, Dasgupta SF, Stella AM, Drieu K, Rapoport SI (2002) Ginkgo biloba extracts EGb 761 and bilobalide increase NADH dehydrogenase mRNA level and mitochondrial respiratory control ratio in PC12 cells. Neurochem Res 27:319–323PubMedGoogle Scholar
  157. Teng W, Wang L, Xue W, Guan C (2009) Activation of TLR4-mediated NFkappaB signaling in hemorrhagic brain in rats. Mediators Inflamm 2009:473276PubMedGoogle Scholar
  158. Tong L, Thornton PL, Balazs R, Cotman CW (2001) Beta -amyloid-(1-42) impairs activity-dependent cAMP-response element-binding protein signaling in neurons at concentrations in which cell survival Is not compromised. J Biol Chem 276:17301–17306PubMedGoogle Scholar
  159. Tsuzuki K, Fukatsu R, Yamaguchi H, Tateno M, Imai K, Fujii N, Yamauchi T (2000) Transthyretin binds amyloid beta peptides, Abeta1-42 and Abeta1-40 to form complex in the autopsied human kidney - possible role of transthyretin for abeta sequestration. Neurosci Lett 281:171–174PubMedGoogle Scholar
  160. Uchida K, Shiraishi M, Naito Y, Torii Y, Nakamura Y, Osawa T (1999) Activation of stress signaling pathways by the end product of lipid peroxidation 4-hydroxy-2-nonenal is a potential inducer of intracellular peroxide production. J Biol Chem 274:2234–2242PubMedGoogle Scholar
  161. Uríková A, Babusíková E, Dobrota D, Drgová A, Kaplán P, Tatarková Z, Lehotský J (2006) Impact of Ginkgo Biloba Extract EGb 761 on ischemia/reperfusion – induced oxidative stress products formation in rat forebrain. Cell Mol Neurobiol 26:1343–1353PubMedGoogle Scholar
  162. Usai S, Grazzi L, Bussone G (2011) Gingkolide B as migraine preventive treatment in young age: results at 1-year follow-up. Neurol Sci 32(Suppl 1):S197–S199PubMedGoogle Scholar
  163. Viles JH, Klewpatinond M, Nadal RC (2008) Copper and the structural biology of the prion protein. Biochem Soc Trans 36:1288–1292PubMedGoogle Scholar
  164. Watanabe CM, Wolffram S, Ader P, Rimbach G, Packer L, Maguire JJ, Schultz PG, Gohil K (2001) The in vivo neuromodulatory effects of the herbal medicine Ginkgo biloba. Proc Natl Acad Sci USA 98:6577–6580PubMedGoogle Scholar
  165. White HL, Scates PW, Cooper BR (1996) Extracts of Ginkgo biloba leaves inhibit monoamine oxidase. Life Sci 58:1315–1321PubMedGoogle Scholar
  166. Williams B, Watanabe CM, Schultz PG, Rimbach G, Krucker T (2004) Age-related effects of Ginkgo biloba extract on synaptic plasticity and excitability. Neurobiol Aging 25:955–962PubMedGoogle Scholar
  167. Wilson JF (2007) In the clinic: migraine. Ann Intern Med 147:ITC11-1–ITC11-16Google Scholar
  168. Winter JC, Timineri D (1999) The discriminative stimulus properties of EGb 761, an extract of Ginkgo biloba. Pharmacol Biochem Behav 62:543–547PubMedGoogle Scholar
  169. Woelkart K, Fetzimayr E, Dittrich P, Beubler E, Pinl F, Suter A, Bauer R (2010) Pharmacokinetics of bilobalide, ginkgolide A and B after administration of three different Ginkgo biloba L. preparations in humans. Phytother Res 24:445–450PubMedGoogle Scholar
  170. Wu GY, Deisseroth K, Tsien RW (2001) Activity-dependent CREB phosphorylation: convergence of a fast sensitive calmodulin kinase pathway and a slow less sensitive mitogen-activated protein kinase pathway. Proc Natl Acad Sci USA 98:2808–2813PubMedGoogle Scholar
  171. Xin W-J, Wei T-T, Chen C, Ni Y-C, Zhao B-L, Hou J-W (2000) Mechanisms of apoptosis in rat cerebellar granule cells induced by hydroxyl radicals and effects of Egb761 and its constitutes. Toxicology 148:103–110PubMedGoogle Scholar
  172. Xu JP, Rui YC, Li TJ (1999) Antagonistic effects of Ginkgo biloba extract on adhesion of monocytes and neutrophils to cultured cerebral microvascular endothelial cells. Zhongguo Yao Li Xue Bao 20:423–425PubMedGoogle Scholar
  173. Xu Y, Cui C, Pang C, Christen Y, Luo Y (2007) Restoration of impaired phosphorylation of cyclic AMP response element-binding protein (CREB) by EGb 761 and its constituents in Abeta-expressing neuroblastoma cells. Eur J Neurosci 26:2931–2939PubMedGoogle Scholar
  174. Yagmur E, Piatkowski A, Groger A, Pallua N, Gressner AM, Kiefer P (2005) Bleeding complication under Ginkgo biloba medication. Am J Hematol 79:343–344PubMedGoogle Scholar
  175. Yoo DY, Nam Y, Kim W, Yoo KY, Park J, Lee CH, Choi JH, Yoon YS, Kim DW, Won MH, Hwang IK (2011) Effects of Ginkgo biloba extract on promotion of neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice. J Vet Med Sci 73:71–76PubMedGoogle Scholar
  176. Yeh KY, Pu HF, Kaphle K, Lin SF, Wu LS, Lin JH, Tsai YF (2008) Ginkgo biloba extract enhances male copulatory behavior and reduces serum prolactin levels in rats. Horm Behav 53:225–231PubMedGoogle Scholar
  177. Yoshitake T, Yoshitake S, Kehr J (2010) The Ginkgo biloba extract EGb 761® and its main constituent flavonoids and ginkgolides increase extracellular dopamine levels in the rat prefrontal cortex. Br J Pharmacol 159:659–668PubMedGoogle Scholar
  178. Zambrano N, Minopoli G, Duilio A, De Renzis S, Cimino F, Russo T (1997) DNA-binding protein Pur alpha and transcription factor YY1 function as transcription activators of the neuron-specific FE65 gene promoter. Biochem J 328:293–300PubMedGoogle Scholar
  179. Zhuang H, Pin S, Christen Y, Doré S (2002) Induction of heme oxygenase 1 by Ginkgo biloba in neuronal cultures and potential implications in ischemia. Cell Mol Biol (Noisy-le-grand) 48:647–653Google Scholar
  180. Zhao X, Zhang Y, Strong R, Zhang J, Grotta JC, Aronowski J (2007) Distinct patterns of intracerebral hemorrhage-induced alterations in NF-_B subunit, iNOS, and COX-2 expression. J Neurochem 101:652–663PubMedGoogle Scholar
  181. Zhao Z, Liu N, Huang J, Lu RH, Xu XM (2011) Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death. J Neurochem 116:1057–1065PubMedGoogle Scholar
  182. Zhou W, Chai H, Courson A, Lin PH, Lumsden AB, Yao Q, Chen C (2006) Ginkgolide A attenuates homocysteine-induced endothelial dysfunction in porcine coronary arteries. J Vasc Surg 44:853–862PubMedGoogle Scholar
  183. Zimmermann M, Colciaghi F, Cattabeni F, Di Luca M (2002) Ginkgo biloba extract: from molecular mechanisms to the treatment of Alzheimer disease. Cell Mol Biol 48:613–623PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Akhlaq A. Farooqui
    • 1
  1. 1.Department of Molecular and Cellular BiochemistryOhio State UniversityColumbusUSA

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