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.
Highlights
Daphnetin (7,8-dihydroxycoumarin, Dap, Figure 1A) extracted from Daphne odora Var. marginata (D. marginata) mainly contains coumarin compounds
NMDA receptor has been proven to be involved in the pathogenesis of neurodegenerative disorders associated with glutamate excitotoxicity
The neurons exposed to NMDA (200 μM) for 30 min induced significant cell injury as shown by the cell viability measured by the MTT assay
Summary
Daphnetin (7,8-dihydroxycoumarin, Dap, Figure 1A) extracted from Daphne odora Var. marginata (D. marginata) mainly contains coumarin compounds. Among these coumarins, daphnetin has been reported to make important contributions to the analgesic and anti-inflammatory activity of Daphne odora [1]. Daphnetin has been reported to make important contributions to the analgesic and anti-inflammatory activity of Daphne odora [1] It has been clinically used in the treatment of coagulation disorders and rheumatoid arthritis [2]. The aim of this study was to investigate the possible protective efficacy of Dap in neuronal apoptosis induced by NMDA receptor activation and to elucidate the underlying mechanisms. We found that pretreatment of Dap significantly attenuated exitotoxicity by depressing the apoptotic signaling pathways
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
