Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans.
Amyloid-beta (Abeta) 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 Abeta-induced apoptosis in neuroblastoma cells. In this study, we use EGb 761 and its single constituents to associate Abeta species with Abeta-induced pathological behaviors in a model organism, Caenorhabditis elegans. We report that EGb 761 and one of its components, ginkgolide A, alleviates Abeta-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 Abeta oligomerization and Abeta deposits in the worms. Moreover, reducing oxidative stress is not the mechanism by which EGb 761 and ginkgolide A suppress Abeta-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 Abeta-related pathological behaviors, (2) the protection against Abeta toxicity by EGb 761 is mediated primarily by modulating Abeta oligomeric species, and (3) ginkgolide A has therapeutic potential for prevention and treatment of AD.
Wu
Yanjue
Y
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA.
Wu
Zhixin
Z
Butko
Peter
P
Christen
Yves
Y
Lambert
Mary P
MP
Klein
William L
WL
Link
Christopher D
CD
Luo
Yuan
Y
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000494:pharmacology*; D010291:Paresis / Q000139:chemically induced / Q000517:prevention & control; D010936:Plant Extracts / Q000494:pharmacology*; D000096983:Ginkgo Extract
D016229:Amyloid beta-Peptides; D046934:Ginkgolides; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract