Protective Role of Deoxyschizandrin and Schisantherin A against Myocardial Ischemia-Reperfusion Injury in Rats

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. Methodology/Principal Findings: Anesthetized male rats were treated once with DSD and STA (each 40 mmol/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/dt(max) 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/Significance: 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.