title: A natural coumarin derivative esculetin offers neuroprotection on cerebral ischemia/reperfusion injury in mice.
abstract: Previous studies have demonstrated that a natural coumarin compound esculetin (Esc) possesses antioxidant, anti-tumor, and anti-inflammation activities and rescues cultured primary neurons from NMDA toxicity. In this study, we investigated the neuroprotective effects of Esc on cerebral ischemia/reperfusion (I/R) injury in a middle cerebral artery occlusion model in mice. Esc (20 μg) was administered intracerebroventricularly at 30 min before ischemia. We found that Esc significantly reduced infarct volume and decreased neurological deficit scores after 75 min of ischemia and 24 h of reperfusion. Post-treatment of Esc still provided neuroprotection even when Esc was administered after 4 h of reperfusion. Our data also indicated that intraperitoneal administration of Esc showed protective effects on cerebral I/R injury in a dose-dependent manner. We further explored the protective mechanisms of Esc on cerebral I/R injury and found that Esc decreased cleaved caspase 3 level, a marker of apoptosis. Finally, our data demonstrated that Esc exerted its anti-apoptotic activity by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax, two apoptosis-related proteins. Because of its clinical use as an anticoagulant and its safety profile, Esc may have a therapeutic potential for the treatment of stroke in the future clinical trials.
authors.affiliation: Department of Anesthesiology, the Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Aijie
authors.initials: A
authors.lastname: Pei
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Hailong
authors.initials: H
authors.lastname: Yu
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Sun
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
authors.forename: Xingshun
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D014468:Umbelliferones; C007628:esculetin