title: Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats.
abstract: BACKGROUND
  Traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizaeare are prescribed together for their putative cardioprotective effects in clinical practice. However, the rationale of the combined use remains unclear. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms.
  
  
  METHODS
  Paeonol (80 mg kg(-1)) and danshensu (160 mg kg(-1)) were administered orally to Sprague Dawley rats in individual or in combination for 21 days. At the end of this period, rats were administered isoproterenol (85 mg kg(-1)) subcutaneously to induce myocardial injury. After induction, rats were anaesthetized with pentobarbital sodium (35 mg kg(-1)) to record electrocardiogram, then sacrificed and biochemical assays of the heart tissues were performed.
  
  
  RESULTS
  Induction of rats with isoproterenol resulted in a marked (P<0.001) elevation in ST-segment, infarct size, level of serum marker enzymes (CK-MB, LDH, AST and ALT), cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GR, and GST) and protein expression of Bcl-2. Pretreatment with paeonol and danshensu combination showed a significant (P<0.001) decrease in ST-segment elevation, infarct size, cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants and protein expression of Bcl-2 and Nrf2 when compared with individual treated groups.
  
  
  CONCLUSIONS
  This study demonstrates the cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial infarction in rats. The mechanism might be associated with the enhancement of antioxidant defense system through activating of Nrf2 signaling and anti-apoptosis through regulating Bax, Bcl-2 and Caspase-3. It could provide experimental evidence to support the rationality of combinatorial use of traditional Chinese medicine in clinical practice.
authors.affiliation: Institute of Materia Medica, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Xie
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.forename: Si-Wang
authors.initials: SW
authors.lastname: Wang
authors.forename: Bang-Le
authors.initials: BL
authors.lastname: Zhang
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bi
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Sun
authors.forename: Shan
authors.initials: S
authors.lastname: Miao
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Xuan-Xuan
authors.initials: XX
authors.lastname: Zhou
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Qiu
mesh_terms: D000098:Acetophenones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D007545:Isoproterenol; D007773:Lactates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism; D014463:Ultrasonography; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D015415:Biomarkers; D002316:Cardiotonic Agents; D007773:Lactates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017392:Thiobarbituric Acid Reactive Substances; D019210:Troponin I; D051028:bcl-2-Associated X Protein; C013638:paeonol; C035055:3,4-dihydroxyphenyllactic acid; D053148:Caspase 3; D005978:Glutathione; D007545:Isoproterenol