Inhibition of amyloid-β aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761 (original) (raw)
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Inhibition of amyloid- aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761
Proceedings of the National Academy of Sciences, 2002
Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, has been used in clinical trials for its beneficial effects on brain functions, particularly in connection with agerelated dementias and Alzheimer's disease (AD). Substantial experimental evidence indicates that EGb761 protects against neuronal damage from a variety of insults, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing an AD-associated double mutation, we report that EGb761 inhibits formation of amyloid- (A) fibrils, which are the diagnostic, and possibly causative, feature of AD.
European Journal of Neuroscience, 2000
Substantial evidence suggests that the accumulation of b-amyloid (Ab)-derived peptides, and to a lesser extent free radicals, may contribute to the aetiology and/or progression of Alzheimer's disease (AD). Ginkgo biloba extract (EGb 761) is a well-de®ned plant extract containing two major groups of constituents, i.e.¯avonoids and terpenoids. It is viewed as a polyvalent agent with a possible therapeutic use in the treatment of neurodegenerative diseases of multifactorial origin, e.g. AD. We have investigated here the potential effectiveness of EGb 761 against toxicity induced by (Ab)-derived peptides (Ab 25±35 , Ab 1±40 and Ab 1±42) on hippocampal primary cultured cells, this area being severely affected in AD. A co-treatment with EGb 761 concentration-dependently (10±100 mg/ mL) protected hippocampal neurons against toxicity induced by Ab fragments, with a maximal and complete protection at the highest concentration tested. Similar, albeit less potent protective effects were seen with the¯avonoid fraction of the extract (CP 205), while the terpenes were ineffective. Most interestingly, EGb 761 (100 mg/mL) was even able to protect (up to 8 h) hippocampal cells from a pre-exposure to Ab 25±35 and Ab 1±40. EGb 761 was also able to both protect and rescue hippocampal cells from toxicity induced by H 2 O 2 (50±150 mM), a major peroxide possibly involved in mediating Ab toxicity. Moreover, EGb 761 (10±100 mg/mL), and to a lesser extent CP 205 (10±50 mg/mL), completely blocked Ab-induced events, e.g. reactive oxygen species accumulation and apoptosis. These results suggest that the neuroprotective effects of EGb 761 are partly associated with its antioxidant properties and highlight its possible effectiveness in neurodegenerative diseases, e.g. AD via the inhibition of Ab-induced toxicity and cell death.
European Journal of Neuroscience, 2000
Substantial evidence suggests that the accumulation of b-amyloid (Ab)-derived peptides, and to a lesser extent free radicals, may contribute to the aetiology and/or progression of Alzheimer's disease (AD). Ginkgo biloba extract (EGb 761) is a well-de®ned plant extract containing two major groups of constituents, i.e.¯avonoids and terpenoids. It is viewed as a polyvalent agent with a possible therapeutic use in the treatment of neurodegenerative diseases of multifactorial origin, e.g. AD. We have investigated here the potential effectiveness of EGb 761 against toxicity induced by (Ab)-derived peptides (Ab 25±35 ,A b 1±40 and Ab 1±42 ) on hippocampal primary cultured cells, this area being severely affected in AD. A co-treatment with EGb 761 concentration-dependently (10±100 mg/ mL) protected hippocampal neurons against toxicity induced by Ab fragments, with a maximal and complete protection at the highest concentration tested. Similar, albeit less potent protective effects were seen with the¯avonoid fraction of the extract (CP 205), while the terpenes were ineffective. Most interestingly, EGb 761 (100 mg/mL) was even able to protect (up to 8 h) hippocampal cells from a pre-exposure to Ab 25±35 and Ab 1±40 . EGb 761 was also able to both protect and rescue hippocampal cells from toxicity induced by H 2 O 2 (50±150 mM), a major peroxide possibly involved in mediating Ab toxicity. Moreover, EGb 761 (10±100 mg/mL), and to a lesser extent CP 205 (10±50 mg/mL), completely blocked Ab-induced events, e.g. reactive oxygen species accumulation and apoptosis. These results suggest that the neuroprotective effects of EGb 761 are partly associated with its antioxidant properties and highlight its possible effectiveness in neurodegenerative diseases, e.g. AD via the inhibition of Ab-induced toxicity and cell death.
Ginkgo biloba extract in Alzheimer's disease: from action mechanisms to medical practice
International journal of molecular sciences, 2010
Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, is one of the most popular herbal supplements. Numerous preclinical studies have shown the neuroprotective effects of EGb761 and support the notion that it may be effective in the treatment and prevention of neurodegenerative disorders such as Alzheimer's disease (AD). Despite the preclinical promise, the clinical efficacy of this drug remains elusive. In this review, possible mechanisms underlying neuroprotective actions of EGb761 are described in detail, together with a brief discussion of the problem of studying this herb clinically to verify its efficacy in the treatment and prevention of AD. Moreover, various parameters e.g., the dosage and the permeability of the blood brain barrier (BBB), impacting the outcome of the clinical effectiveness of the extract are also discussed. Overall, the findings summarized in this review suggest that, a better understanding of the neuroprotective mechanisms of...
Journal of Neuroscience, 2006
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.
The Journal of Neuroscience, 2006
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.
Protection against β-amyloid induced abnormal synaptic function and cell death by Ginkgolide J
Neurobiology of Aging, 2009
A new Ginkgo biloba extract P8A (TTL), 70% enriched with terpene trilactones, prevents Aβ 1-42 induced inhibition of long-term potentiation in the CA1 region of mouse hippocampal slices. This neuroprotective effect is attributed in large part to ginkgolide J that completely replicates the effect of the extract. Ginkgolide J is also capable of inhibiting cell death of rodent hippocampal neurons caused by Aβ 1-42 . This beneficial and multi-faceted mode of action of the ginkgolide makes it a new and promising lead in designing therapies against Alzheimer's disease.
Journal of neuroinflammation, 2017
Ginkgo biloba has been reported to possess free radical-scavenging antioxidant activity and anti-inflammatory properties. In our pilot study, YY-1224, a terpene trilactone-strengthened extract of G. biloba, showed anti-inflammatory, neurotrophic, and antioxidant effects. We investigated the pharmacological potential of YY-1224 in β-amyloid (Aβ) (1-42)-induced memory impairment using cyclooxygenase-2 (COX-2) knockout (-/-) and APPswe/PS1dE9 transgenic (APP/PS1 Tg) mice. Repeated treatment with YY-1224 significantly attenuated Aβ (1-42)-induced memory impairment in COX-2 (+/+) mice, but not in COX-2 (-/-) mice. YY-1224 significantly attenuated Aβ (1-42)-induced upregulation of platelet-activating factor (PAF) receptor gene expression, reactive oxygen species, and pro-inflammatory factors. In addition, YY-1224 significantly inhibited Aβ (1-42)-induced downregulation of PAF-acetylhydrolase-1 (PAF-AH-1) and peroxisome proliferator-activated receptor γ (PPARγ) gene expression. These chang...
Alzheimer's disease (AD) is the most common progressive human neurodegenerative disorder affecting elderly population worldwide. Hence, prevention of AD has been a priority of AD research worldwide. Based on understanding of disease mechanism, different therapeutic strategies involving synthetic and herbal approaches are being used against AD. Among the herbal extract, Ginkgo biloba extract (GBE) is one of the most investigated herbal remedy for cognitive disorders and Alzheimer's disease (AD). Standardized extract of Ginkgo biloba is a popular dietary supplement taken by the elderly population to improve memory and age-related loss of cognitive function. Nevertheless, its efficacy in the prevention and treatment of dementia remains controversial. Specifically, the added effects of GBE in subjects already receiving "conventional" anti-dementia treatments have been to date very scarcely investigated. This review summarizes recent advancements in our understanding of the potential use of Ginkgo biloba extract in the prevention of AD including its antioxidant property. A better understanding of the mechanisms of action of GBE against AD will be important for designing therapeutic strategies, for basic understanding of the underlying neurodegenerative processes, and for a better understanding of the effectiveness and complexity of this herbal medicine.
Acta Oto-Laryngologica, 2010
Standardized Ginkgo biloba extract, EGb761, has been shown to possess polyvalent properties, such as anti-oxidation, anti-apoptosis and anti-inflammation. Recently, it has also been proposed to have direct protective effects on mitochondria. The effects of EGb761 make it a potential anti-aging drug. Despite that, the 'anti-aging' effect of EGb761, particularly its effect on the central nervous system, is still inconclusive. Using two age groups (3-week-old and 40-week-old) of SAMP8 mice (a senescence-accelerated strain of mice), the effects of EGb761 on mitochondrial function in platelets and hippocampi were investigated in this study. It was found that mitochondrial functions, evaluated as cytochrome c oxidase (COX) activity, mitochondrial ATP (adenosine-5 0-triphosphate) content and mitochondrial glutathione (GSH) content, decreased with age. EGb761 protected against mitochondrial dysfunction in platelets of young and old mice, suggesting a peripheral effect of this herb in the prevention and treatment of age-associated degeneration. In contrast, in hippocampi, protective effects of EGb761 were observed only in the old mice, probably due to an age-associated increase in the permeability of the blood brain barrier (BBB). Therefore, while EGb761 has a potential anti-aging effect, its central effect can be affected by in vivo factors such as the BBB permeability. A better understanding of the in vivo pharmacological actions of EGb761 may contribute to a better understanding of the effectiveness and complexity of this drug.