The Efficacy of Ginkgo biloba on Cognitive Function in Alzheimer Disease

Oken, Barry; Storzbach, Daniel; Kaye, Jeffrey

doi:10.1001/archneur.55.11.1409

Cited by 538 publications

(286 citation statements)

References 45 publications

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“…8 EGb has been considered as a polyvalent therapeutic agent in the treatment of disturbances of multifactorial origin, including cerebral insufficiency, 9 mild cognitive impairments in elderly patients, 10 Alzheimer's disease, and vascular dementia. 11,12 Patients have displayed good tolerance for EGb, with no verified adverse drug interactions. 11 EGb has become the most widely sold phytomedicine in Europe and 1 of the 10 best-selling herbal medications in the United States.…”

Section: Human Immunodeficiency Virus (Hiv)-1 Tat Protein Ismentioning

confidence: 98%

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

Zou

Kim

Zhou

et al. 2007

The American Journal of Pathology

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Human immunodeficiency virus (HIV)-1 Tat protein isan important pathogenic factor in HIV-associated neuropathogenesis. Despite recent progress, the molecular mechanisms underlying Tat neurotoxicity are still not completely understood. However, few therapeutics have been developed to specifically target HIV infection in the brain. Recent development of an inducible brain-specific Tat transgenic mouse model has made it possible to define the mechanisms of Tat neurotoxicity and evaluate anti-neuroAIDS therapeutic candidates in the context of a whole organism. Herein, we demonstrate that administration of EGb 761, a standardized formulation of Ginkgo biloba extract, markedly protected Tat transgenic mice from Tat-induced developmental retardation, inflammation, death, astrocytosis, and neuron loss. EGb 761 directly down-regulated glial fibrillary acidic protein (GFAP) expression at both protein and mRNA levels. This down-regulation was, at least in part, attributable to direct effects of EGb 761 on the interactions of the AP1 and NF-B transcription factors with the GFAP promoter. Most strikingly, Tat-induced neuropathological phenotypes including macrophage/microglia activation, central nervous system infiltration of T lymphocytes, and oxidative stress were significantly alleviated in GFAP-null/Tat transgenic mice. Taken together, these results provide the first evidence to support the potential for clinical use of EGb 761 to treat HIV-associated neurological diseases. Moreover, these findings suggest for the first time that GFAP activation is directly involved in Tat neurotoxicity, supporting the notion that astrocyte activation or astrocytosis may directly contribute to HIV-associated neurological disorders.

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Section: Human Immunodeficiency Virus (Hiv)-1 Tat Protein Ismentioning

confidence: 98%

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

Zou

Kim

Zhou

et al. 2007

The American Journal of Pathology

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“…Recent epidemiological and dietary intervention studies in humans and animals suggest that flavonoids may play a useful role in preventing neurodegeneration, especially age-related cognitive, motoric, and mood decline and protect against oxidative stress as well as cerebral ischemia/ reperfusion injuries. Studies in humans using flavonoidcontaining plant extracts, such as Ginkgo biloba, or pure flavonoid preparations demonstrate positive effects on cognitive function and memory performance in healthy volunteers from all age groups [42,97,213] as well as in patients with age-or Alzheimer' disease-associated dementia [128,146,208]. Watanabe et al [211] reported that G. biloba supplementation in mice had neuromodulatory effects as indicated by a more than three-fold increase of mRNA expression for neuronal tyrosine/threonine phosphatases-1, microtubule-associated tau, prolactin, different calcium, and chloride channels as well as transthyretin.…”

Section: Flavonoids: Neuroprotective Agents In Vivo and In Vitro?mentioning

confidence: 99%

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

302

176

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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“…The positive effects of ginkgo extracts are presumed to result from the synergistic action of two distinct classes of constituents, the flavonoids (glycosides of quercetin, kaempferol, and isorhamnetin) and terpenoids (bilobalide, ginkgolides A, B, C, and J) [1].…”

mentioning

confidence: 99%

Simultaneous determination of ginkgo flavonoids and terpenoids in plasma: Ammonium formate in LC mobile phase enhancing electrospray ionization efficiency and capacity

Zhao

Sun

2008

J. Am. Soc. Mass Spectrom.

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Extracts from Ginkgo biloba leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components. We herein describe the development of an LC-MS/MS-based method for simultaneous determination of flavonoids (quercetin, kaempferol, and isorhamnetin) and terpenoids (bilobalide, ginkgolides A, B, C, and J) in acid-hydrolyzed plasma by circumventing cross-interference between the flavonoids and terpenoids identified. Notably, inclusion of ammonium formate (0.2 mM) in the mobile phase generated beneficial LC-electrolyte effects, including increased ESI efficiency and capacity, with the result that the newly developed procedure exhibits the highest analytical performance reported to date for ginkgo-associated studies. The method yields high sensitivity, negligible matrix interference and cross-interference, wide linear dynamic ranges, high sample throughput, and quite small initial sample size. The assay utility to dog pharmacokinetic measurements of commercial ginkgo products yielded the most comprehensive data on systemic exposure to the ginkgo compounds to date. The newly developed multi-analyte procedure should be widely useful. (J

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The Efficacy of Ginkgo biloba on Cognitive Function in Alzheimer Disease

Cited by 538 publications

References 45 publications

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Simultaneous determination of ginkgo flavonoids and terpenoids in plasma: Ammonium formate in LC mobile phase enhancing electrospray ionization efficiency and capacity

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