title: Diosmin protects against cerebral ischemia/reperfusion injury through activating JAK2/STAT3 signal pathway in mice.
abstract: OBJECTIVE
  Apoptosis is a major form of cell death in cerebral ischemia/reperfusion (I/R) pathogenesis and may represent a target for treatment. Diosmin (DM), a micronized purified flavonoid drug, possesses an anti-apoptotic effect in the treatment of varicose veins and renal injury. However, the effect of DM in the acute phase of cerebral I/R is not clear. This study investigated DM's role in cerebral I/R and its potential mechanism.
  
  
  METHODS
  Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO). Experiment 1 was used to evaluate the time course expression of Janus tyrosine kinase-2 (JAK2), signal transducer and activator of transcription-3 (STAT3), phosphorylated JAK2 (pJAK2) and phosphorylated STAT3 (pSTAT3) after cerebral I/R, and six time points were included. In experiment 2, DM was given orally at doses of 50mg/kg or 100mg/kg for 6 consecutive days before receiving tMCAO. At 24h after reperfusion, neurological deficit, Nissl staining, brain water content and infarct volume were examined. Bcl-2, Bax, pJAK2, and pSTAT3 were detected by immunohistochemistry, qRT-PCR and Western blot. Confocal microscope was used to observe the location of pSTAT3 in the cerebral cortex.
  
  
  RESULTS
  Compared with Vehicle group, the high dose of DM significantly alleviated neurological deficit, brain water content, infarct volume, increased the Nissl-positive cells, upregulated the expression of pJAK2, pSTAT3 and Bcl-2 and downregulated Bax (P<0.05).
  
  
  CONCLUSIONS
  These results showed that DM protected against cerebral I/R injury through activating JAK2/STAT3 signal pathway.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
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: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: N
authors.initials: N
authors.lastname: Kang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Cui
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.
authors.forename: L
authors.initials: L
authors.lastname: Cui
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.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China. Electronic address: wangxl2014@yahoo.com.
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004145:Diosmin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053614:Janus Kinase 2 / Q000378:metabolism*; D008297:Male; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D013995:Time; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051028:bcl-2-Associated X Protein; D004145:Diosmin; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
keywords: JAK2/STAT3; apoptosis; cerebral ischemia/reperfusion; diosmin