title: Pretreatment by evodiamine is neuroprotective in cerebral ischemia: up-regulated pAkt, pGSK3β, down-regulated NF-κB expression, and ameliorated BBB permeability.
abstract: Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Evodiamine (Evo) has been proved to elicit a variety of biological effects through its anti-inflammatory property in the treatment of infectious disease, Alzheimer's disease and hypoxia-induced inflammatory response. Whether this protective effect applies to cerebral ischemic injury, we therefore investigated the potential neuroprotective role of Evo and the underlying mechanisms. Male Institute of Cancer Research (ICR) mice were subjected to permanent middle cerebral artery occlusion (pMCAO) and randomly divided into five groups: Sham (sham-operated + 1% DMSO + 0.5% tween80), pMCAO (pMCAO + 0.9% saline), Vehicle (pMCAO + 1% DMSO + 0.5% tween80), Evo-L (Vehicle + Evo 50 mg/kg) and Evo-H (Vehicle + Evo 100 mg/kg) groups. Evo was administered intragastrically twice daily for 3 days, and once again 30 min before mouse brain ischemia was induced by pMCAO. Neurological deficit, brain water content and infarct size were measured at 24 h after stroke. The expression of pAkt, pGSK3β, NF-κB and claudin-5 in ischemic cerebral cortex was analyzed by western blot and qRT-PCR. Compared with Vehicle group, Evo significantly ameliorated neurological deficit, brain water content and infarct size, upregulated the expression of pAkt, pGSK3β and claudin-5, and downregulated the nuclear accumulation of NF-κB (P < 0.05). Evo protected the brain from ischemic damage caused by pMCAO; this effect may be through upregulation of pAkt, pGSK3β and claudin-5, and downregulation of NF-κB expression.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, Hebei, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Xumeng
authors.initials: X
authors.lastname: Zhao
authors.forename: Linyu
authors.initials: L
authors.lastname: Chen
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010936:Plant Extracts / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D011799:Quinazolines / Q000008:administration & dosage*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D010936:Plant Extracts; D011799:Quinazolines; C049639:evodiamine; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3