title: A metabonomic study of cardioprotection of ginsenosides, schizandrin, and ophiopogonin D against acute myocardial infarction in rats.
abstract: BACKGROUND
  Metabonomics is a useful tool for studying mechanisms of drug treatment using systematic metabolite profiles. Ginsenosides Rg1 and Rb1, ophiopogonin D, and schizandrin are the main bioactive components of a traditional Chinese formula (Sheng-Mai San) widely used for the treatment of coronary heart disease. It remains unknown the effect of individual bioactive component and how the multi-components in combination affect the treating acute myocardial infarction (AMI).
  
  
  METHODS
  Rats were divided into 7 groups and dosed consecutively for 7 days with mono and combined-therapy administrations. Serum samples were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Partial least squares discriminate analysis (PLS-DA) was employed to distinguish the metabolic profile of rats in different groups and identify potential biomarkers.
  
  
  RESULTS
  Score plots of PLS-DA exhibited that combined-therapy groups were significantly different from AMI group, whereas no differences were observed for mono-therapy groups. We found that AMI caused comprehensive metabolic changes involving stimulation of glycolysis, suppression of fatty acid oxidation, together with disturbed metabolism of arachidonic acid, linoleate, leukotriene, glycerophospholipid, phosphatidylinositol phosphate, and some amino acids. β-hydroxybutyrate, cholines and glucose were regulated by mono-therapy of schizandrin and ginsenosides respectively. Besides these metabolites, combined-therapy ameliorated more of the AMI-induced metabolic changes including glycerol, and O-acetyl glycoprotein. A remarkable reduction of lactate suggested the therapeutic effect of combined-therapy through improving myocardial energy metabolism.
  
  
  CONCLUSIONS
  This study provided novel metabonomic insights on the mechanism of synergistic cardioprotection of combined-therapy with ginsenosides, schizandrin, and ophiopogonin D, and demonstrated the potential of discovering new drugs by combining bioactive components from traditional Chinese formula.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Jiang
authors.forename: Liyuan
authors.initials: L
authors.lastname: Kang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 88 Yuquan Road, Nankai District, Tianjin 300193, China. lizheng1@gmail.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D034242:Cyclooctanes / Q000737:chemistry / Q000494:pharmacology*; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome / Q000187:drug effects; D055432:Metabolomics; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D013150:Spirostans / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D034242:Cyclooctanes; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D017705:Lignans; D011083:Polycyclic Compounds; D012503:Saponins; D013150:Spirostans; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; C046996:ophiopogonin D; C011105:schizandrin