title: Targeted metabolomic profiling of cardioprotective effect of Ginkgo biloba L. extract on myocardial ischemia in rats.
abstract: BACKGROUND
  Myocardial ischemia (MI) is one of the highest mortality diseases in the world. It is closely associated with metabolism disorders of endogenous substances. Ginkgo biloba L. extract (GBE) is a popular herbal medicine used for prevention and therapy of MI. But its regulation effect on the metabolism disorders caused by MI remains currently unknown.
  
  
  OBJECTIVE
  Our metabolomic profiling study provided insight into endogenous metabolic disorders of MI and cardioprotective mechanisms of GBE.
  
  
  METHODS
  The rats were preventive administrated of GBE (200mg/kg, i.g.) for 4 weeks and then subcutaneous injected of isoproterenol to establish MI model. Heart marker enzymes and histopathological examination were adopted to evaluate MI model and effect of GBE. On this base, endogenous metabolites in rat plasma and heart were well profiled using the developed targeted metabolomic profiling platform to comprehensively analyze metabolic pathways and find biomarkers.
  
  
  METHODS
  A targeted metabolomic profiling platform was developed and only 100μl biological sample was used to quantify 808 metabolites covering the core network of lipid, energy, amino acid and nucleotide metabolism. Then using this platform, endogenous metabolites of rats undergoing MI model and GBE pre-treatment were well profiled. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between groups and find biomarkers.
  
  
  RESULTS
  The metabolomic profiles of MI model rats pre-protected by GBE were significantly different from those of unprotected. 47 metabolites were found as potential biomarkers and indicated MI would lead to disturbed metabolism due to inflammation, oxidative stress and structural damage; while GBE could effectively restore fatty acid, sphingolipid, phosphoglyceride, glyceride, amino acid and energy metabolism, closely related to its antioxidant, PAF antagonist and hypolipidemic properties.
  
  
  CONCLUSIONS
  The cardioprotective effect of GBE can be achieved through the comprehensive regulation of multiple metabolic pathways.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: zhjl@imm.ac.cn.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Tiankun
authors.initials: T
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry; D006321:Heart / Q000187:drug effects*; D008297:Male; D055432:Metabolomics; D017202:Myocardial Ischemia / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts
keywords: Cardioprotective effect; Ginkgo biloba L. extract; High-performance liquid chromatography–mass spectrometry; Metabolomic; Myocardial ischemia