Ginkgo biloba extract and its flavonol and terpenelactone fractions do not affect beta-secretase mRNA and enzyme activity levels in cultured neurons and in 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.
Augustin
Sabine
S
Institute of Animal Nutrition and Physiology, Christian Albrechts University of Kiel, Kiel, Germany.
Huebbe
Patricia
P
Matzner
Nicole
N
Augustin
Kay
K
Schliebs
Reinhard
R
Cermak
Rainer
R
Wolffram
Siegfried
S
Rimbach
Gerald
G
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D002478:Cells, Cultured; D005260:Female; D044948:Flavonols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020441:Ginkgo biloba; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D012333:RNA, Messenger / Q000032:analysis; D000096983:Ginkgo Extract
D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D044948:Flavonols; D010936:Plant Extracts; D012333:RNA, Messenger; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C509282:Bace1 protein, mouse