title: Ginsenoside Rd attenuates myocardial ischemia/reperfusion injury via Akt/GSK-3β signaling and inhibition of the mitochondria-dependent apoptotic pathway.
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.
authors: Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors: Yang
authors: Y
authors: Wang
authors: Xu
authors: X
authors: Li
authors: Xiaoliang
authors: X
authors: Wang
authors: Waynebond
authors: W
authors: Lau
authors: Yajing
authors: Y
authors: Wang
authors: Yuan
authors: Y
authors: Xing
authors: Xing
authors: X
authors: Zhang
authors: Xinliang
authors: X
authors: Ma
authors: Feng
authors: F
authors: Gao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D002232:Carbocyanines; D002316:Cardiotonic Agents / Q000494:pharmacology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D036145:Ginsenosides / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001562:Benzimidazoles; D002232:Carbocyanines; D002316:Cardiotonic Agents; D005456:Fluorescent Dyes; D036145:Ginsenosides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D020169:Caspases; C049863:ginsenoside Rd
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