Effects of <i>Ginkgo biloba</i> extract (EGb 761) on gene expression: Possible relevance to neurological disorders and age‐associated cognitive impairment

DeFeudis, F.V.

doi:10.1002/ddr.10151

Cited by 35 publications

(27 citation statements)

References 171 publications

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“…Neuroprotection by EGb 761 is known as a "multipotent" action (i.e., it is achieved by modulating a variety of biological pathways simultaneously because of its complex nature) (DeFeudis, 2002;Smith and Luo, 2003). We next asked whether the inhibitory effect on oligomerization by an individual constituent is sufficient to correlate with its alleviative effect on A␤-induced paralysis.…”

Section: Egb 761 Modulates A␤ Oligomers In the Transgenic C Elegansmentioning

confidence: 99%

“…Currently, a National Institutes of Health-supported GEM (Ginkgo Evaluation of Memory) study in the United States and a GuidAge study in Europe are underway to evaluate EGb 761 as a preventive drug (DeKosky et al, 2006). Substantial experimental data indicate that EGb 761 has neuroprotective and neuromodulatory effects (Luo, 2001;Watanabe et al, 2001;Yao et al, 2001;DeFeudis, 2002). Two of its major constituents, flavonoids (24%) and terpenoids (6%), have been actively investigated for their neuroprotective properties (DeFeudis, 1998;Smith and Luo, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Amyloid-β-Induced Pathological Behaviors Are Suppressed byGinkgo bilobaExtract EGb 761 and Ginkgolides in TransgenicCaenorhabditis elegans

Wu¹,

Wu²,

Butko³

et al. 2006

J. Neurosci.

368

366

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Amyloid-␤ (A␤) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that the standardized Ginkgo biloba extract EGb 761, commonly used to enhance memory and by AD patients for dementia, inhibits A␤-induced apoptosis in neuroblastoma cells. In this study, we use EGb 761 and its single constituents to associate A␤ species with A␤-induced pathological behaviors in a model organism, Caenorhabditis elegans. We report that EGb 761 and one of its components, ginkgolide A, alleviates A␤-induced pathological behaviors, including paralysis, and reduces chemotaxis behavior and 5-HT hypersensitivity in a transgenic C. elegans. We also show that EGb 761 inhibits A␤ oligomerization and A␤ deposits in the worms. Moreover, reducing oxidative stress is not the mechanism by which EGb 761 and ginkgolide A suppress A␤-induced paralysis because the antioxidant L-ascorbic acid reduced intracellular levels of hydrogen peroxide to the same extent as EGb 761, but was not nearly as effective in suppressing paralysis in the transgenic C. elegans. These findings suggest that (1) EGb 761 suppresses A␤-related pathological behaviors, (2) the protection against A␤ toxicity by EGb 761 is mediated primarily by modulating A␤ oligomeric species, and (3) ginkgolide A has therapeutic potential for prevention and treatment of AD.

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Section: Egb 761 Modulates A␤ Oligomers In the Transgenic C Elegansmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Amyloid-β-Induced Pathological Behaviors Are Suppressed byGinkgo bilobaExtract EGb 761 and Ginkgolides in TransgenicCaenorhabditis elegans

Wu¹,

Wu²,

Butko³

et al. 2006

J. Neurosci.

368

366

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“…47, 48 EGb 761 has been shown to alter expression of a number of host genes. 49 Recent cDNA microarray stud- For NO experiments, primary astrocytes were prepared and exposed to Dox (5 g/ml) for 3 days, and the culture supernatants were collected to determine NO production using a Griess assay. Distilled H 2 O with the same pH was used as the control (Ϫ).…”

Section: Regulation Of Gfap Expression In Astrocytes By Egb 761mentioning

confidence: 99%

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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“…Numerous studies have shown that EGb 761 can counteract the detrimental effects of oxidative damage caused by free radicals and related ROS [e.g., Chatterjee, 1985;DeFeudis et al, 1985;Pincemail et al, 1989;Pietri et al, 1997;Soulie et al, 2002; see also reviews by DeFeudis, 1991DeFeudis, , 1998DeFeudis, , 2002Christen, 2000]. This ''oxidative stress'' that is overcome by EGb 761 occurs when free radicals and related ROS are present in excess and may be due to increased free radical formation and/or decreased activity of endogenous antioxidant activity.…”

Section: Antioxidant Effects Of Egb 761 In Relation To Stressmentioning

confidence: 98%

“Stress‐alleviating” and “vigilance‐enhancing” actions of Ginkgo biloba extract (EGb 761)

DeFeudis¹,

Drieu

2004

Drug Development Research

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This overview is focused on the stress-alleviating and vigilance-enhancing properties of Ginkgo biloba extract (EGb 761) that have been observed in animal models and in humans and that appear useful in explaining the therapeutic effects of the extract on non-cognitive brain functions that may be reflective of mood changes. With regard to its stress-alleviating activity, in rodents EGb 761 facilitates behavioral adaptation, decreases circulating levels of corticosterone, catecholamines, ACTH, and CRH, suppresses the expression of the mitochondrial peripheral benzodiazepine receptor of the adrenal cortex, increases the anxiolytic activity of diazepam, increases arousal by an action that may involve GABA A receptor antagonism, induces anxiolytic-like activity, prevents stress-induced desensitization of hippocampal 5-HT 1A receptors, suppresses the down-regulation of hippocampal glucocorticoid receptors, and facilitates decision-making. In humans, EGb 761 has vigilance-enhancing effects that support its clinical use in treating disorders involving stress-induced brain dysfunction and those non-cognitive symptoms of dementia currently classified as ''behavioral and psychological symptoms of dementia'' (BPSD). Collectively, these findings indicate that EGb 761 is useful for treating symptoms that are now classified as components of BPSD. As drug combinations consisting of EGb 761 and a non-selective cholinesterase inhibitor, an antidepressant drug, or a neuroleptic could possibly be even more useful in treating BPSD, evaluation of such therapy is recommended. Drug Dev.

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Effects of Ginkgo biloba extract (EGb 761) on gene expression: Possible relevance to neurological disorders and age‐associated cognitive impairment

Cited by 35 publications

References 171 publications

Amyloid-β-Induced Pathological Behaviors Are Suppressed byGinkgo bilobaExtract EGb 761 and Ginkgolides in TransgenicCaenorhabditis elegans

Amyloid-β-Induced Pathological Behaviors Are Suppressed byGinkgo bilobaExtract EGb 761 and Ginkgolides in TransgenicCaenorhabditis elegans

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

“Stress‐alleviating” and “vigilance‐enhancing” actions of Ginkgo biloba extract (EGb 761)

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