Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity

Molecules

Le Yang²  Qi Yang²  Kun Zhang²  Yu-JiaoLi²  Yu-Mei Wu²  Shui-Bing Liu²  Lian-He Zheng¹ 

[1] Department Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, Xi’an 710032, China;Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China; E-Mails:

关键词: daphnetin;    excitotoxicity;    neuron;    apoptosis;    calcium;   

DOI  :  10.3390/molecules190914542

来源: mdpi

【 摘 要 】

The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced excitotoxicity. We evaluated the neuroprotective activities in the primary cultured cortical neurons against NMDA-induced excitotoxicity. Pretreatment with Dap significantly prevented NMDA-induced neuronal cell loss. Dap significantly inhibited the neuronal apoptosis by regulating balance of Bcl-2 and Bax expression. Furthermore, pretreatment of Dap reversed the up-regulation of NR2B-containing NMDA receptors and inhibited the intracellular Ca²⁺ overload induced by NMDA exposure. In addition, Dap prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion in vivo. The findings suggest that Dap prevents the excitotoxicity through inhibiting the NR2B-containing NMDA receptors and the subsequent calcium overload in cultured cortical neurons.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.