Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761.
Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, has been used in clinical trials for its beneficial effects on brain functions, particularly in connection with age-related dementias and Alzheimer's disease (AD). Substantial experimental evidence indicates that EGb761 protects against neuronal damage from a variety of insults, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing an AD-associated double mutation, we report that EGb761 inhibits formation of amyloid-beta (Abeta) fibrils, which are the diagnostic, and possibly causative, feature of AD. The decreased Abeta fibrillogenesis in the presence of EGb761 was observed both in the conditioned medium of this Abeta-secreting cell line and in solution in vitro. In the cells, EGb761 significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of caspase 3, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that (i) neuronal damage in AD might be due to two factors: a direct Abeta toxicity and the apoptosis initiated by the mitochondria; and (ii) multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of Abeta aggregation, underlie the neuroprotective effects of EGb761.
Luo
Yuan
Y
Departments of Biological Sciences and Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA. yuan.luo@usm.edu
Smith
Julie V
JV
Paramasivam
Vijaykumar
V
Burdick
Adam
A
Curry
Kenneth J
KJ
Buford
Justin P
JP
Khan
Ikhlas
I
Netzer
William J
WJ
Xu
Huaxi
H
Butko
Peter
P
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D020441:Ginkgo biloba; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D000096983:Ginkgo Extract
D016229:Amyloid beta-Peptides; D053148:Caspase 3; D020169:Caspases; D046911:Macromolecular Substances; D018696:Neuroprotective Agents; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C505407:CASP3 protein, human