title: An-Gong-Niu-Huang Wan protects against cerebral ischemia induced apoptosis in rats: up-regulation of Bcl-2 and down-regulation of Bax and caspase-3.
abstract: BACKGROUND
  The An-Gong-Niu-Huang Wan (AGNH), a Chinese traditional medicine, has been used for treatment of cerebral diseases for centuries in China and other Asian countries, and is approved by the State Food and Drug Administration of China for the treatment of stroke. The aim of present study is to test the neuroprotective effects of AGNH on cerebral ischemia in rats and to explore the underlying mechanisms.
  
  
  METHODS
  75 Male Sprague-Dawley rats were randomly divided into 5 groups: sham, ischemia-reperfusion (I/R), and I/R plus 0.065 g/kg/d AGNH, 0.125 g/kg/d AGNH and 0.25 g/kg/d AGNH. Cerebral ischemia was induced by 1.5h of middle cerebral artery occlusion (MCAO). Neurological functional deficits were evaluated according to Zea longa׳s score, cerebral infarct area was measured by tetrazolium staining. Cell injury and apoptosis were assessed by Nissl staining and DNA fragmentation assay. The expression of Bax, Bcl-2 and caspase-3 were analyzed by Western blot.
  
  
  RESULTS
  Rats subjected to MCAO exhibited worsened neurological score, infarct area, cell damage and apoptosis. These were all attenuated by AGNH (0.125 and 0.25 g/kg/d). Moreover, AGNH reversed cerebral ischemia induced decreases in Bcl-2 expression and increases in Bax and caspase-3 expression.
  
  
  CONCLUSIONS
  These results suggest that AGNH exerts neuroprotective effects, and the neuroprotection is likely to relate to depressed Bax/Bcl-2 ratio and caspase-3 level, leading to inhibition of apoptotic cell death.
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Lan
authors.affiliation: Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xin-De
authors.initials: XD
authors.lastname: Zhen
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: xiang.jun@zs-hospital.sh.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: dingfangcai@163.com.
authors.forename: Ding-Fang
authors.initials: DF
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008516:Medicine, Chinese Traditional; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C000594495:an-gong-niu-huang wan; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: An-Gong-Niu-Huang Wan; Apoptosis; Cerebral ischemia; Traditional Chinese medicine