Amyloid-B-Induced Pathological Behaviors Are Suppressed by Ginkgo biloba Extract EGb 761 and Ginkgolides in Transgenic Caenorhabditis elegans

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[Note: Amyloid beta is the main constituent of amyloid plaques in the brains of Alzheimer’s patients. Study concludes component of Ginkgo biloba extract “has therapeutic potential for prevention and treatment of Alzheimer’s disease.”]

Journal: The Journal of Neuroscience. December 13, 2006. 26(50); 13102-13113. [E-publication ahead of print]

Authors and affiliations: Wu Y, Wu Z, Butko P, Christen Y, Lambert MP, Klein WL, Link CD, Luo Y. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland (Y Wu, Luo); Departments of Biological Sciences (Z Wu) and Chemistry and Biochemistry (Butko), University of Southern Mississippi, Hattiesburg, Mississippi; Ipsen, Paris, France (Christen); Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois (Lambert, Klein); Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado (Link). [E-mail: yluo@rx.umaryland.edu ]

DOI:10.1523/JNEUROSCI.3448-06.2006

Amyloid-B (AB) 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 Alzheimer’s disease patients for dementia, inhibits AB-induced apoptosis in neuroblastoma cells.

In this study, we use Ginkgo biloba extract EGb 761 and its single constituents to associate AB species with Amyloid-B-induced pathological behaviors in a model organism, Caenorhabditis elegans.

We report that Ginkgo biloba extract EGb 761 and one of its components, ginkgolide A, alleviates AB-induced pathological behaviors, including paralysis, and reduces chemotaxis behavior and 5-HT hypersensitivity in a transgenic C. elegans.

We also show that Ginkgo biloba extract EGb 761 inhibits AB oligomerization and AB deposits in the worms. Moreover, reducing oxidative stress is not the mechanism by which EGb 761 and ginkgolide A suppress AB-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. Ginkgo biloba extract EGb 761 suppresses AB-related pathological behaviors,
2. The protection against AB toxicity by EGb 761 is mediated primarily by modulating AB oligomeric species, and
3. Ginkgolide A [a component of Ginkgo biloba extract EGb 761] has therapeutic potential for prevention and treatment of Alzheimer’s disease.

Key words: AB peptide, Alzheimer's disease, behavior, mutant, phenotype, serotonin

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