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

J Ethnopharmacol. 2014 May 28;154(1):156-62. doi: 10.1016/j.jep.2014.03.057. Epub 2014 Mar 29.

Abstract

Ethnopharmacological relevance: 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.

Materials and 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.

Keywords: An-Gong-Niu-Huang Wan; Apoptosis; Cerebral ischemia; Traditional Chinese medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain / drug effects
  • Brain / pathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Caspase 3 / metabolism
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Infarction, Middle Cerebral Artery
  • Male
  • Medicine, Chinese Traditional
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Phytotherapy
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats, Sprague-Dawley
  • Up-Regulation
  • bcl-2-Associated X Protein / metabolism

Substances

  • Drugs, Chinese Herbal
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • an-gong-niu-huang wan
  • bcl-2-Associated X Protein
  • Casp3 protein, rat
  • Caspase 3