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Molecules 2014, 19(9), 14542-14555;

Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity

Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
Department Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 7 July 2014 / Revised: 4 August 2014 / Accepted: 6 August 2014 / Published: 15 September 2014
(This article belongs to the Section Natural Products Chemistry)
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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. View Full-Text
Keywords: daphnetin; excitotoxicity; neuron; apoptosis; calcium daphnetin; excitotoxicity; neuron; apoptosis; calcium

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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.

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