title: Daphnetin, a natural coumarin derivative, provides the neuroprotection against glutamate-induced toxicity in HT22 cells and ischemic brain injury.
abstract: 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.
authors.affiliation: Department of Neurology and Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Du
authors.forename: Hui
authors.initials: H
authors.lastname: Tu
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Li
authors.forename: Aijie
authors.initials: A
authors.lastname: Pei
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Miao
authors.forename: Jizhen
authors.initials: J
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Xingshun
authors.initials: X
authors.lastname: Xu
authors.forename: Heqing
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D014468:Umbelliferones; D018698:Glutamic Acid; D013482:Superoxide Dismutase; D005978:Glutathione; C039952:daphnetin