title: Differential cardioprotective effects of salvianolic acid and tanshinone on acute myocardial infarction are mediated by unique signaling pathways.
abstract: BACKGROUND
  Salvianolic acid (SAL) and tanshinone (TAN) are major hydrophilic and lipophilic compounds, respectively, from one herbal medicine, Danshen, which has been widely and successfully used for treating cardiovascular diseases in Asian countries. Because few studies have reported different molecular mechanisms between the different compounds in same herb, we investigate if separate molecular pathways are involved in cardioprotective effect by different active components of Danshen.
  
  
  METHODS
  We used an acute myocardial infarction (MI) model to compare the cardioprotective effects of SAL and TAN in rats. Both infarct size and echocardiographic response were evaluated at 3, 7, 14 and 28 days after surgery. Genes involved in ischemic injury and in responses to SAL or TAN treatment in ischemic hearts were identified by microarray analysis and verified by quantitative real-time RT-PCR.
  
  
  RESULTS
  Results showed that both SAL and TAN delay the development of ischemia by decreasing infarct size and improving systolic function post MI. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated different kinetics and gene expression profiles by SAL and TAN. SAL acts in a later period after ischemia, and its effect is probably mediated by downregulation of genes involved in oxidative stress, certain G-protein coupled receptor activities and apoptosis. On the other hand, TAN acts relatively early after ischemic injury and its effect is at least in part mediated by inhibition of intracellular calcium, cell adhesion and alternative complement pathway. Strikingly, we found that TAN, a recently identified member of selective estrogen receptor modifier (SERM), indeed regulates genes known to be involved in estrogen metabolism post MI.
  
  
  CONCLUSIONS
  Although both SAL and TAN contribute to the cardioprotective effect of Danshen, there are significant mechanistic and temporal differences between the two: TAN acts at an early stage after ischemic injury mainly by inhibition of intracellular calcium and cell adhesion pathways whereas SAL acts mainly by down-regulating apoptosis.
authors.affiliation: Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Limin
authors.initials: L
authors.lastname: Hu
authors.forename: Guanwei
authors.initials: G
authors.lastname: Fan
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Li
authors.forename: Xiumei
authors.initials: X
authors.lastname: Gao
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D003170:Complement Pathway, Alternative / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004967:Estrogens / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007773:Lactates / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D046228:Microarray Analysis; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010618:Phenanthrolines / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013599:Systole / Q000187:drug effects / Q000502:physiology
chemical_list: D045784:Abietanes; D002109:Caffeic Acids; D002317:Cardiovascular Agents; D004365:Drugs, Chinese Herbal; D004967:Estrogens; D007773:Lactates; D010618:Phenanthrolines; D020845:Selective Estrogen Receptor Modulators; C021751:tanshinone; C028972:dan-shen root extract; C066201:salvianolic acid A; D002118:Calcium