title: Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice.
abstract: Carvacrol (CAR), a naturally occurring monoterpenic phenol and food additive, has been shown to have antimicrobials, antitumor, and antidepressant-like activities. A previous study demonstrated that CAR has the ability to protect liver against ischemia/reperfusion injury in rats. In this study, we investigated the protective effects of CAR on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that CAR (50 mg/kg) significantly reduced infarct volume and improved neurological deficits after 75 min of ischemia and 24 h of reperfusion. This neuroprotection was in a dose-dependent manner. Post-treatment with CAR still provided protection on infarct volume when it was administered intraperitoneally at 2 h after reperfusion; however, intracerebroventricular post-treatment reduced infarct volume even when the mice were treated with CAR at 6 h after reperfusion. These findings indicated that CAR has an extended therapeutic window, but delivery strategies may affect the protective effects of CAR. Further, we found that CAR significantly decreased the level of cleaved caspase-3, a marker of apoptosis, suggesting the anti-apoptotic activity of CAR. Finally, our data indicated that CAR treatment increased the level of phosphorylated Akt and the neuroprotection of CAR was reversed by a PI3K inhibitor LY-294002, demonstrating the involvement of the PI3K/Akt pathway in the anti-apoptotic mechanisms of CAR. Due to its safety and wide use in the food industry, CAR is a promising agent to be translated into clinical trials.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, People's Republic of China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Yu
authors.forename: Zeng-Li
authors.initials: ZL
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Aijie
authors.initials: A
authors.lastname: Pei
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.forename: Xuanchen
authors.initials: X
authors.lastname: Qian
authors.forename: Jinjiang
authors.initials: J
authors.lastname: He
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; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D000081007:Cymenes; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005503:Food Additives / Q000008:administration & dosage / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053148:Caspase 3; D002867:Chromones; D000081007:Cymenes; D004791:Enzyme Inhibitors; D005503:Food Additives; D039821:Monoterpenes; D009025:Morpholines; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C073316:carvacrol; C505409:Casp3 protein, mouse