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Molecules 2014, 19(9), 14542-14555; https://doi.org/10.3390/molecules190914542

Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity

1
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China
2
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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Abstract

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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