title: Protective role of deoxyschizandrin and schisantherin A against myocardial ischemia-reperfusion injury in rats.
abstract: BACKGROUND
  Our previous studies suggested that deoxyschizandrin (DSD) and schisantherin A (STA) may have cardioprotective effects, but information in this regard is lacking. Therefore, we explored the protective role of DSD and STA in myocardial ischemia-reperfusion (I/R) injury.
  
  
  RESULTS
  Anesthetized male rats were treated once with DSD and STA (each 40 µmol/kg) through the tail vein after 45 min of ischemia, followed by 2-h reperfusion. Cardiac function, infarct size, biochemical markers, histopathology and apoptosis were measured and mRNA expression of gp91 (phox) in myocardial tissue assessed by RT-PCR. Neonatal rat cardiomyocytes were pretreated with DSD and STA and then damaged by H2O2. Cell apoptosis was tested by a flow cytometric assay. Compared with the I/R group: (i) DSD and STA could significantly reduce the abnormalities of LVSP, LVEDP, ±dp/dtmax and arrhythmias, thereby showing their protective roles in cardiac function; (ii) DSD and STA could significantly attenuate the infarct size and MDA release while increasing SOD activity, suggesting a role in reducing myocardial injury; (iii) tissue morphology and myocardial textual analysis revealed that DSD and STA mitigated changes in myocardial histopathology; (iv) DSD and STA decreased apoptosis (33.56±2.58% to 10.28±2.80% and 10.98±1.99%, respectively) and caspase-3 activity in the myocardium (0.62±0.02 OD/mg to 0.38±0.02 OD/mg and 0.32±0.02 OD/mg, respectively), showing their protective effects upon cardiomyocytes; and (v) DSD and STA had similar protective effects on I/R injury as those seen with the positive control metoprolol. In vitro, DSD and STA could significantly decrease the apoptosis of neonatal cardiomyocytes.
  
  
  CONCLUSIONS
  These data suggest that DSD and STA can protect against myocardial I/R injury. The underlining mechanism may be related to their role in inhibiting cardiomyocyte apoptosis.
authors.affiliation: College of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi Province, China.
authors.forename: Ruimiao
authors.initials: R
authors.lastname: Chang
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Xingxin
authors.initials: X
authors.lastname: Yang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yue
authors.forename: Lili
authors.initials: L
authors.lastname: Dou
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Wang
authors.forename: Weifang
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D034242:Cyclooctanes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019610:Cytoprotection / Q000187:drug effects; D004149:Dioxoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017705:Lignans / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D008562:Membrane Glycoproteins; D011083:Polycyclic Compounds; D012333:RNA, Messenger; D008315:Malondialdehyde; C034734:schizandrin A; C034557:schizandrer A; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D053148:Caspase 3