title: Ginsenoside Rd Attenuates DNA Damage by Increasing Expression of DNA Glycosylase Endonuclease VIII-like Proteins after Focal Cerebral Ischemia.
abstract: BACKGROUND
  Ginsenoside Rd (GSRd), one of the main active ingredients in traditional Chinese herbal Panax ginseng, has been found to have therapeutic effects on ischemic stroke. However, the molecular mechanisms of GSRd's neuroprotective function remain unclear. Ischemic stroke-induced oxidative stress results in DNA damage, which triggers cell death and contributes to poor prognosis. Oxidative DNA damage is primarily processed by the base excision repair (BER) pathway. Three of the five major DNA glycosylases that initiate the BER pathway in the event of DNA damage from oxidation are the endonuclease VIII-like (NEIL) proteins. This study aimed to investigate the effect of GSRd on the expression of DNA glycosylases NEILs in a rat model of focal cerebral ischemia.
  
  
  METHODS
  NEIL expression patterns were evaluated by quantitative real-time polymerase chain reaction in both normal and middle cerebral artery occlusion (MCAO) rat models. Survival rate and Zea-Longa neurological scores were used to assess the effect of GSRd administration on MCAO rats. Mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damages were evaluated by the way of real-time analysis of mutation frequency. NEIL expressions were measured in both messenger RNA (mRNA) and protein levels by quantitative polymerase chain reaction and Western blotting analysis. Apoptosis level was quantitated by the expression of cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling assay.
  
  
  RESULTS
  We found that GSRd administration reduced mtDNA and nDNA damages, which contributed to an improvement in survival rate and neurological function; significantly up-regulated NEIL1 and NEIL3 expressions in both mRNA and protein levels of MCAO rats; and reduced cell apoptosis and the expression of cleaved caspase-3 in rats at 7 days after MCAO.
  
  
  CONCLUSIONS
  Our results indicated that the neuroprotective function of GSRd for acute ischemic stroke might be partially explained by the up-regulation of NEIL1 and NEIL3 expressions.
authors: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032; Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors: Long-Xiu
authors: LX
authors: Yang
authors: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Xiao
authors: X
authors: Zhang
authors: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Gang
authors: G
authors: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology*; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D036145:Ginsenosides / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D036145:Ginsenosides; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C049863:ginsenoside Rd