title: Bicyclol upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia.
abstract: Oxidative damage plays a detrimental role in the pathophysiology of cerebral ischemia and may represent a therapeutic target. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) controls the coordinated expression of the important antioxidant and detoxification genes through a promotor sequence termed the antioxidant response element. Bicyclol has been proved to elicit a variety of biological effects through its antioxidant and anti-inflammatory properties. But the underlying mechanisms are poorly understood. In this study, the role of bicyclol in cerebral ischemia and its potential mechanism were investigated.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly assigned to five groups: MCAO (middle cerebral artery occlusion), Vehicle (MCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50mg/kg), By-H (Vehicle+bicyclol 100mg/kg) and Sham operated groups. Bicyclol was administered intragastrically once a day for 3 consecutive days; after 1h of bicyclol pretreatment on the third day, rat ischemic stroke was induced by MCAO. Neurological deficit, infarct volume, and brain edema were detected at 24h after stroke. Western blot and RT-qPCR were used to measure the expression of Nrf2, HO-1 and SOD1. MDA was detected by the spectrophotometer.
  
  
  RESULTS
  Compared with MCAO group, By-H group significantly ameliorated neurological deficit, lessened the infarct volume and brain edema, increased the expression of Nrf2, HO-1 and SOD1 (P<0.05), and decreased the content of MDA (P<0.05).
  
  
  CONCLUSIONS
  Bicyclol protected the rat brain from ischemic damage caused by MCAO, and this effect may be through the upregulation of the transcription factor Nrf2 expression.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China. Electronic address: zhang6xj@aliyun.com.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Xumeng
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Linyu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; C477843:bicyclol; D051547:Heme Oxygenase-1
keywords: BW; Bicyclol; By; GSH; GST; HO-1; I/R; Ischemic stroke; MCA; MCAO; MDA; Nrf2; Oxidative; ROS; SD; SOD1; bicyclol; brain water content; glutathione; glutathione S-transferase; heme oxygenase 1; ischemia/reperfusion; malondialdehyde; middle cerebral artery; middle cerebral artery occlusion; nuclear factor erythroid 2-related factor 2; pMCAO; permanent middle cerebral artery occlusion; reactive oxygen species; standard deviation; superoxide dismutase 1