Journal
NEUROCHEMICAL RESEARCH
Volume 39, Issue 2, Pages 269-275Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-013-1218-6
Keywords
Stroke; Daphnetin; Glutathione; Superoxide dismutase
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Funding
- National Natural Science Foundation of China [30700245, 81071095, 813111078]
- Suzhou science and technology development program [SYS201232]
- Priority Academic Program Development of Jiangsu Higher Education Institutions of China
- Jiangsu Key Laboratory of Translational Research [BM2013003]
- Jiangsu Province's Key Provincial Talents Program
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Daphnetin (DAP), a coumarin derivative, has been reported to have multiple pharmacological actions including analgesia, antimalarial, anti-arthritic, and anti-pyretic properties. It is unclear whether DAP has neuroprotective effects on ischemic brain injury. In this study, we found that DAP treatment (i.c.v.) reduced the infarct volume at 24 h after ischemia/reperfusion injury and improved neurological behaviors in a middle cerebral artery occlusion mouse model. Moreover, we provided evidences that DAP had protective effects on infarct volume in neonate rats even it was administrated at 4 h after cerebral hypoxia/ischemia injury. To explore its neuroprotective mechanisms of DAP, we examined the protection of DAP on glutamate toxicity-induced cell death in hippocampal HT-22 cells. Our results demonstrated that DAP protected against glutamate toxicity in HT-22 cells in a concentration-dependent manner. Further, we found that DAP maintained the cellular levels of glutathione and superoxide dismutase activity, suggesting the anti-oxidatant activity of DAP. Since DAP has been used for the treatment of coagulation disorder and rheumatoid arthritis for long time with a safety profile, DAP will be a promising agent for the treatment of stroke.
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