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Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons
journal contribution
posted on 2018-12-12, 00:00 authored by Li-Chen Kuo, Yan-Qing Song, Chien-An Yao, Irene H. Cheng, Chiang-Ting Chien, Guan-Chiun Lee, Wen-Chin Yang, Yenshou LinUtilizing the N-methyl-d-aspartate (NMDA) receptor antagonist as a strategy, memantine
is the only agent available for clinically treating mild to severe
Alzheimer’s disease (AD). Our aim was to develop novel similar
herb-based drugs. Using a screening platform, ginkgolide A (GA), a
pure compound extracted from Ginkgo biloba, was found to attenuate amyloid β (Aβ)-induced abnormal
depolarization in mouse primary cortical neurons. Using receptor agonists,
it was determined that GA inhibits both NMDA receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid receptors. Furthermore, the Aβ-induced increase in c-Jun
N-terminal kinase phosphorylation in neurons was prevented by GA.
Body weight, glutamate oxaloacetate transaminase, glutamic–pyruvic
transaminase, liver histology, and kidney histology were similar when
the wild-type/AD animal model mice with and without GA treatment were
compared. This pure compound improves the memory of wild-type mice.
Our findings indicate that GA has great potential clinically for the
treatment of AD because it might target NMDA receptors just like memantine.