No abstract

The standardised Ginkgo biloba extract EGb761 is known for its potential beneficial effects in the prevention and therapy of neurodegenerative disorders including Alzheimer’s disease (AD). However, the molecular mechanisms and the specific role of its constituents are largely unknown. The aim of the present feeding trial was to investigate the effects of EGb761 and its major constituents on the expression of genes encoding for proteins involved in the pathogenesis of AD in mouse brain. Six month old C57B6 mice were fed semi synthetic diets enriched with either EGb761 or one of its main fractions, flavonols and terpenelactones, respectively, over a period of 4 weeks. Thereafter, mRNA of α-secretase, neprilysin, amyloid precursor protein (App), App binding protein-1 and acetylcholine esterase was quantified in hippocampus and cortex. EGb761 and its flavonol fraction had no effects on relative mRNA levels of the respective genes in mouse brain. However, the terpenelactone fraction significantly decreased the mRNA levels of App in the hippocampus. Taken together, a 4 week dietary treatment with EGb761 or its main fractions had only moderate effects on mRNA levels of AD related genes in cortex and hippocampus of mice.

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 (A beta) as amyloid plaques in the brain. A beta is a cleavage product of amyloid precursor protein (APP). Certain proteases, called beta-secretases (BACE), are crucial in the formation of A beta. 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.