Abstract
Evidence suggests Ginsenoside Rd (GSRd), a biologically active extract from the medical plant Panax Ginseng, exerts antioxidant effect, decreasing reactive oxygen species (ROS) formation. Current study determined the effect of GSRd on myocardial ischemia/reperfusion (MI/R) injury (a pathological condition where ROS production is significantly increased) and investigated the underlying mechanisms. The current study utilized an in vivo rat model of MI/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of simulated ischemia/reperfusion (SI/R) injury. Infarct size was measured by Evans blue/TTC double staining. NRC injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. ROS accumulation and apoptosis were assessed by flow cytometry. Mitochondrial membrane potential (MMP) was determined by 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetrathylbenzimidazol carbocyanine iodide (JC-1). Cytosolic translocation of mitochondrial cytochrome c and expression of caspase-9, caspase-3, Bcl-2 family proteins, and phosphorylated Akt and GSK-3β were determined by western blot. Pretreatment with GSRd (50 mg/kg) significantly augmented rat cardiac function, as evidenced by increased left ventricular ejection fraction (LVEF) and ±dP/dt. GSRd reduced myocardial infarct size, apoptotic cell death, and blood creatine kinase/lactate dehydrogenase levels after MI/R. In NRCs, GSRd (10 µM) inhibited SI/R-induced ROS generation (P<0.01), decreased cellular apoptosis, stabilized the mitochondrial membrane potential (MMP), and attenuated cytosolic translocation of mitochondrial cytochrome c. GSRd inhibited activation of caspase-9 and caspase-3, increased the phosphorylated Akt and GSK-3β, and increased the Bcl-2/Bax ratio. Together, these data demonstrate GSRd mediated cardioprotective effect against MI/R–induced apoptosis via a mitochondrial-dependent apoptotic pathway.
Highlights
Ginseng, the root of Panax ginseng C.A
Ginsenoside Rd improves rat cardiac function after myocardial ischemia- reperfusion (MI/R) GSRd had no effects on blood glucose, blood pressure and cardiac function in the absence of MI/R
There were no significant differences in heart rate (HR) and mean arterial pressure (MAP) between any groups during MI/R
Summary
The root of Panax ginseng C.A. Mayer (Araliaceae), is a popular traditional Chinese medicinal herb. The mechanisms responsible for ginseng’s various effects remain largely unknown, several active ingredients termed ginsenosides have been isolated from the plant [1,2,3]. D-glucopyranosyl-(1R2)-b-D-gluco-pyranoside (GSRd, C48H82O18?3H2O, molecular weight 1001, Figure 1), one of the major P. ginseng isolates, scavenges free radicals [4,5], inhibits Ca2+-influx via receptor and store-operated Ca2+ channels [6], and protects against neuronal apoptosis [4,7]. In addition to being highly lipophilic and capable of diffusing across biological membranes, GSRd may have significant advantageous cardiac effects. It has not been investigated whether GSRd exerts protective effect against myocardial ischemia- reperfusion (MI/R) injury, or by what potential mechanisms
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