Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity
AbstractThe 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. View Full-Text
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Yang, L.; Yang, Q.; Zhang, K.; Li, Y.-J.; Wu, Y.-M.; Liu, S.-B.; Zheng, L.-H.; Zhao, M.-G. Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity. Molecules 2014, 19, 14542-14555.
Yang L, Yang Q, Zhang K, Li Y-J, Wu Y-M, Liu S-B, Zheng L-H, Zhao M-G. Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity. Molecules. 2014; 19(9):14542-14555.Chicago/Turabian Style
Yang, Le; Yang, Qi; Zhang, Kun; Li, Yu-Jiao; Wu, Yu-Mei; Liu, Shui-Bing; Zheng, Lian-He; Zhao, Ming-Gao. 2014. "Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity." Molecules 19, no. 9: 14542-14555.