title: The edaravone and 3-n-butylphthalide ring-opening derivative 10b effectively attenuates cerebral ischemia injury in rats.
abstract: OBJECTIVE
  Compound 10b is a hybrid molecule of edaravone and a ring-opening derivative of 3-n-butylphthalide (NBP). The aim of this study was to examine the effects of compound 10b on brain damage in rats after focal cerebral ischemia.
  
  
  METHODS
  SD rats were subjected to 2-h-middle cerebral artery occlusion (MCAO). At the onset of reperfusion, the rats were orally treated with NBP (60 mg/kg), edaravone (3 mg/kg), NBP (60 mg/kg)+edaravone (3 mg/kg), or compound 10b (70, 140 mg/kg). The infarct volume, motor behavior deficits, brain water content, histopathological alterations, and activity of GSH, SOD, and MDA were analyzed 24 h after reperfusion. The levels of relevant proteins in the ipsilateral striatum were examined using immunoblotting.
  
  
  RESULTS
  Administration of compound 10b (70 or 140 mg/kg) significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound 10b were more pronounced compared to NBP, edaravone or NBP+edaravone. Furthermore, compound 10b significantly upregulated the protein levels of the cytoprotective molecules Bcl-2, HO-1, Nrf2, Trx, P-NF-κB p65, and IκB-α, while decreasing the expression of Bax, caspase 3, caspase 9, Txnip, NF-κB p65, and P-IκB-α.
  
  
  CONCLUSIONS
  Oral administration of compound 10b effectively attenuates rat cerebral ischemia injury.
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hua
authors.affiliation: 1] State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China [2] Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lin-na
authors.initials: LN
authors.lastname: Wang
authors.affiliation: 1] State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China [2] Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yi-hua
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: 1] State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China [2] Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhang-jian
authors.initials: ZJ
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000077553:Edaravone; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014867:Water / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001572:Benzofurans; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014867:Water; C027125:3-n-butylphthalide; D000077553:Edaravone; D000983:Antipyrine