title: Neuroprotective effects of daphnetin against NMDA receptor-mediated excitotoxicity.
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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yanglefmmu@163.com.
authors.forename: Le
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yangqifmmu@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. kunzhang1900@163.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yujiao_li@126.com.
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yumeiwu@fmmu.edu.cn.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. liushb1974@aliyun.com.
authors.forename: Shui-Bing
authors.initials: SB
authors.lastname: Liu
authors.affiliation: Department Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lian-He
authors.initials: LH
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. minggao@fmmu.edu.cn.
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism* / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D061251:Primary Cell Culture; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014468:Umbelliferones / Q000008:administration & dosage*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016194:Receptors, N-Methyl-D-Aspartate; D014468:Umbelliferones; D051028:bcl-2-Associated X Protein; D018698:Glutamic Acid; D016202:N-Methylaspartate; C039952:daphnetin