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Pharmacology
Original Paper | Planta Med 2008; 74: 6-13
DOI: 10.1055/s-2007-993776 |
© Georg Thieme Verlag KG Stuttgart · New York |
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Ginkgo biloba Extract and its Flavonol and Terpenelactone Fractions do not Affect β-Secretase mRNA and Enzyme Activity Levels in Cultured Neurons and in Mice |
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| Sabine Augustin1, Patricia Huebbe2, Nicole Matzner2, Kay Augustin2, Reinhard Schliebs3, Rainer Cermak4, Siegfried Wolffram1, Gerald Rimbach2 |
1 Institute of Animal Nutrition and Physiology, Christian Albrechts University of Kiel, Kiel, Germany
2 Institute of Human Nutrition and Food Science, Christian Albrechts University of Kiel, Kiel, Germany
3 University of Leipzig, Institute for Brain Research, Department of Neurochemistry, Leipzig, Germany
4 University of Leipzig, Institute for Veterinary Physiology, Leipzig, Germany |
Abstract
Numerous clinical trials have reported beneficial effects of the Ginkgo biloba extract EGb761 in the prevention and therapy of cognitive disorders including Alzheimer's disease (AD). Although neuroprotective properties of EGb761 have been consistently reported, the molecular mechanisms of EGb761 and the specific role of its major constituents, the flavonols and terpenlactones, are largely unknown. One major hallmark of AD is the deposition of amyloid-beta (Aβ) as amyloid plaques in the brain. Aβ is a cleavage product of amyloid precursor protein (APP). Certain proteases, called β-secretases (BACE), are crucial in the formation of Aβ. The purpose of the present study was to investigate the efficacy of EGb761 and its flavonol and terpenelactone fraction to modulate BACE-1 enzyme activity and mRNA levels in vitro and in vivo. Neither EGb761 nor its fractions affected BACE-1 activity in vitro. Furthermore, also in Neuro-2a cells and wild-type as well as transgenic (Tg2576) laboratory mice, no significant effect of EGb761 on BACE-1 enzyme activity and mRNA levels were observed. Current findings suggest that BACE-1 may not be a major molecular target of EGb761 and its flavonol and terpenelactone fraction.
Key words
Ginkgo biloba - Ginkgoaceae - EGb761 - β-secretase - Alzheimer's disease - amyloid-beta - Tg2576
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