Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons
journal contributionposted on 12.12.2018 by Li-Chen Kuo, Yan-Qing Song, Chien-An Yao, Irene H. Cheng, Chiang-Ting Chien, Guan-Chiun Lee, Wen-Chin Yang, Yenshou Lin
Any type of content formally published in an academic journal, usually following a peer-review process.
Utilizing 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.