title: The Ginkgo biloba extract EGb 761 rescues the PC12 neuronal cells from beta-amyloid-induced cell death by inhibiting the formation of beta-amyloid-derived diffusible neurotoxic ligands.
abstract: beta Amyloid (Abeta) treatment induced free radical production and increased glucose uptake, apoptosis and cell death in PC12 nerve cells. Addition of the standardized extract of Ginkgo biloba leaves, EGb 761 together with the Abeta protein prevented, in a dose-dependent manner, the Abeta-induced free radical production, increased glucose uptake, apoptosis and cell death. However, pretreatment of the cells with EGb 761 did not rescue the cells from the Abeta-induced toxicity although it prevented the Abeta-induced reactive oxygen species generation. Moreover, the terpene and flavonoid-free EGb 761 extract, HE 208, although inhibited the Abeta-induced increased glucose uptake, it failed to protect the cells from apoptosis and cytotoxicity induced by Abeta. In conclusion, these results indicate that the terpenoid and flavonoid constituents of EGb 761, acting probably in combination with components present in HE 208, are responsible for rescuing the neuronal cells from Abeta-induced apoptosis and cell death; their mechanism of action being distinct of their antioxidant properties. Because pre- and post-treatment with EGb 761 did not protect the cells from Abeta-induced neurotoxicity, we examined whether EGb 761 interacts directly with Abeta. Indeed, in vitro reconstitution studies demonstrated that EGb 761 inhibits, in a dose-dependent manner, the formation of beta-amyloid-derived diffusible neurotoxic soluble ligands (ADDLs), suggested to be involved in the pathogenesis of Alzheimer's disease.
authors.affiliation: Division of Hormone Research, Departments of Cell Biology, Pharmacology, and Neuroscience, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yao
authors.forename: K
authors.initials: K
authors.lastname: Drieu
authors.forename: V
authors.initials: V
authors.lastname: Papadopoulos
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D020441:Ginkgo biloba; D005947:Glucose / Q000378:metabolism; D008024:Ligands; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D016716:PC12 Cells; D010936:Plant Extracts; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000096983:Ginkgo Extract
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001973:Bromodeoxyuridine; D003847:Deoxyglucose; D005419:Flavonoids; D005947:Glucose; D008024:Ligands; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract