title: Neuroprotective Effect of Scutellarin on Ischemic Cerebral Injury by Down-Regulating the Expression of Angiotensin-Converting Enzyme and AT1 Receptor.
abstract: OBJECTIVE
  Previous studies have demonstrated that angiotensin-converting enzyme (ACE) is involved in brain ischemic injury. In the present study, we investigated whether Scutellarin (Scu) exerts neuroprotective effects by down-regulating the Expression of Angiotensin-Converting Enzyme and AT1 receptor in a rat model of permanent focal cerebral ischemia.
  
  
  METHODS
  Adult Sprague-Dawley rats were administrated with different dosages of Scu by oral gavage for 7 days and underwent permanent middle cerebral artery occlusion (pMCAO). Blood pressure was measured 7 days after Scu administration and 24 h after pMCAO surgery by using a noninvasive tail cuff method. Cerebral blood flow (CBF) was determined by Laser Doppler perfusion monitor and the neuronal dysfunction was evaluated by analysis of neurological deficits before being sacrificed at 24 h after pMCAO. Histopathological change, cell apoptosis and infarct area were respectively determined by hematoxylin-eosin staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end labeling (TUNEL) analysis and 2,3,5-triphenyltetrazolium chloride staining. Tissue angiotensin II (Ang II) and ACE activity were detected by enzyme-linked immunosorbent assays. The expression levels of ACE, Ang II type 1 receptor (AT1R), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured by Western blot and real-time PCR. ACE inhibitory activity of Scu in vitro was detected by the photometric determination.
  
  
  RESULTS
  Scu treatment dose-dependently decreased neurological deficit score, infarct area, cell apoptosis and morphological changes induced by pMCAO, which were associated with reductions of ACE and AT1R expression and the levels of Ang II, TNF-α, IL-6, and IL-1β in ischemic brains. Scu has a potent ACE inhibiting activity.
  
  
  CONCLUSIONS
  Scu protects brain from acute ischemic injury probably through its inhibitory effect on the ACE/Ang II/AT1 axis, CBF preservation and proinflammation inhibition.
authors.affiliation: Pharmacy School, Shihezi University, Shihezi, China.|Department of Pharmacy, the First Division Hospital of Xinjiang Production and Construction Corps, Aksu, Xinjiang, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Neurological Disease, Zhanjiang Medical College, Zhanjiang, Guangdong, China.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Pharmacy School, Shihezi University, Shihezi, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Han
authors.affiliation: Weifang Medical University, Weifang, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Pharmacy School, Shihezi University, Shihezi, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Ren
authors.affiliation: Institute of Neurological Disease, Zhanjiang Medical College, Zhanjiang, Guangdong, China.
authors.forename: Qunwen
authors.initials: Q
authors.lastname: Pan
authors.affiliation: College of Life Sciences, Northwest A&F University, Yangling, Shanxi, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Pharmacy School, Shihezi University, Shihezi, China.|Binzhou Medical University, Yantai, China.
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D005965:Glucuronates / Q000494:pharmacology / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005965:Glucuronates; D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; C484876:scutellarin; D047310:Apigenin; D007703:Peptidyl-Dipeptidase A