Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity
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 neuroprotectiv...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2014-09-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/19/9/14542 |
| _version_ | 1819237161978822656 |
|---|---|
| author | Le Yang Qi Yang Kun Zhang Yu-Jiao Li Yu-Mei Wu Shui-Bing Liu Lian-He Zheng Ming-Gao Zhao |
| author_facet | Le Yang Qi Yang Kun Zhang Yu-Jiao Li Yu-Mei Wu Shui-Bing Liu Lian-He Zheng Ming-Gao Zhao |
| author_sort | Le Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T13:15:56Z |
| format | Article |
| id | doaj.art-7d04b84a92ea4245a302332af0547c1f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-23T13:15:56Z |
| publishDate | 2014-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7d04b84a92ea4245a302332af0547c1f2022-12-21T17:45:36ZengMDPI AGMolecules1420-30492014-09-01199145421455510.3390/molecules190914542molecules190914542Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated ExcitotoxicityLe Yang0Qi Yang1Kun Zhang2Yu-Jiao Li3Yu-Mei Wu4Shui-Bing Liu5Lian-He Zheng6Ming-Gao Zhao7Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, ChinaDepartment Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, ChinaThe 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.http://www.mdpi.com/1420-3049/19/9/14542daphnetinexcitotoxicityneuronapoptosiscalcium |
| spellingShingle | Le Yang Qi Yang Kun Zhang Yu-Jiao Li Yu-Mei Wu Shui-Bing Liu Lian-He Zheng Ming-Gao Zhao Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity Molecules daphnetin excitotoxicity neuron apoptosis calcium |
| title | Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity |
| title_full | Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity |
| title_fullStr | Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity |
| title_full_unstemmed | Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity |
| title_short | Neuroprotective Effects of Daphnetin against NMDA Receptor-Mediated Excitotoxicity |
| title_sort | neuroprotective effects of daphnetin against nmda receptor mediated excitotoxicity |
| topic | daphnetin excitotoxicity neuron apoptosis calcium |
| url | http://www.mdpi.com/1420-3049/19/9/14542 |
| work_keys_str_mv | AT leyang neuroprotectiveeffectsofdaphnetinagainstnmdareceptormediatedexcitotoxicity AT qiyang neuroprotectiveeffectsofdaphnetinagainstnmdareceptormediatedexcitotoxicity AT kunzhang neuroprotectiveeffectsofdaphnetinagainstnmdareceptormediatedexcitotoxicity AT yujiaoli neuroprotectiveeffectsofdaphnetinagainstnmdareceptormediatedexcitotoxicity AT yumeiwu neuroprotectiveeffectsofdaphnetinagainstnmdareceptormediatedexcitotoxicity AT shuibingliu neuroprotectiveeffectsofdaphnetinagainstnmdareceptormediatedexcitotoxicity AT lianhezheng neuroprotectiveeffectsofdaphnetinagainstnmdareceptormediatedexcitotoxicity AT minggaozhao neuroprotectiveeffectsofdaphnetinagainstnmdareceptormediatedexcitotoxicity |