title: Neuroprotective effect of early and short-time applying sophoridine in pMCAO rat brain: down-regulated TRAF6 and up-regulated p-ERK1/2 expression, ameliorated brain infaction and edema.
abstract: BACKGROUND
  Matrine has been proven to protect ischemic injury in brain and sophoridine (SOP) is an isomeride of matrine. It is unknown whether SOP has this protective effect on ischemic injury in brain. We therefore investigated the potential neuroprotective role of SOP and the underlying mechanism.
  
  
  METHODS
  Male, Sprague-Dawley rats were randomly assigned into five groups: Vehicle (pMCAO+saline), High dose (pMCAO+SOP 10 mg/kg), Middle dose (pMCAO+SOP 5 mg/kg), Low dose (pMCAO+SOP 2.5 mg/kg) and Sham operated group. Permanent middle cerebral artery occlusion (pMCAO) model was used and SOP was administered intraperitoneally immediately after cerebral ischemia and once daily in the following days. Neurological deficit was evaluated using a modified six point scale; brain water content and infarct volume were measured. The expression of TRAF6 and ERK1/2 were measured by immunohistochemistry, Western blotting.
  
  
  RESULTS
  Compared with Vehicle group, the cerebral edema was alleviated in High dose group (P<0.05), and the infarct volume was decreased in Low dose group (P<0.05). Consistent with these results, immunohistochemistry and Western blot analysis indicated that TRAF6 expression was significantly decreased in SOP administrated groups at 24 h, and the expression of phosphorylated ERK1/2 increased in Low dose at 72 h.
  
  
  CONCLUSIONS
  SOP protected the brain from damage caused by pMCAO, and this effect may be through down-regulation of TRAF6 expression and up-regulation of ERK1/2 phosphorylation expression.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.
authors.forename: Zongjie
authors.initials: Z
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.forename: Lipeng
authors.initials: L
authors.lastname: Dong
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Xing
authors.forename: Chaohui
authors.initials: C
authors.lastname: Wang
authors.forename: Huimin
authors.initials: H
authors.lastname: Qiao
authors.forename: Linyu
authors.initials: L
authors.lastname: Chen
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D015536:Down-Regulation; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D015854:Up-Regulation; D000093842:Matrines
chemical_list: D000470:Alkaloids; D018696:Neuroprotective Agents; D011807:Quinolizines; D048029:TNF Receptor-Associated Factor 6; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000093842:Matrines