title: Ginsenoside Rg3 attenuates myocardial ischemia/reperfusion injury via Akt/endothelial nitric oxide synthase signaling and the B‑cell lymphoma/B‑cell lymphoma‑associated X protein pathway.
abstract: Previous studies have suggested that ginsenoside Rg3 (GSRg3) extract from the medicinal plant Panax ginseng, may increase nitric oxide production via increases in the phosphorylation and expression of endothelial nitric oxide synthase (eNOS). The present study used an in vitro neonatal rat cardiomyocyte (NRC) model of anoxia‑reoxygenation injury and an in vivo rat model of myocardial ischemia/reperfusion (MI/R) injury. Hemodynamic, histopathological and biochemical assessment of the myocardial injury was performed and the expression levels of lactate dehydrogenase (LDH), superoxide dismutase and creatine kinase (CK) were measured in serum from the animal model, which may reflect myocardial injury. NRC injury was determined using a Cell Counting kit‑8. The GSRg3 anti‑apoptotic effects were assessed using flow cytometry to investigate the number of early‑late apoptotic cells and western blot analysis was performed to analyze the protein expression levels of caspase‑3, caspase‑9, B‑cell lymphoma‑2 (Bcl‑2), phosphorylated (p‑)Akt and eNOS. The results suggested that pretreatment with GSRg3 (60 mg/kg) significantly improved rat cardiac function, as demonstrated by increased left ventricular systolic pressure, heart rate and first derivative of left ventricular pressure. GSRg3 also reduced the size of the myocardial infarct and LDH/CK levels in the blood following MI/R. In vitro investigations revealed that GSRg3 (10 mM) decreased NRC apoptosis through inhibiting the activation of caspase‑3 and caspase‑9, and increasing the expression levels of p‑Akt, eNOS and the ratio of Bcl‑2/Bcl‑2‑associated X protein (Bax). Overall, the present study revealed that GSRg3 mediated a cardioprotective effect against MI/R‑induced apoptosis via Akt/eNOS signaling and the Bcl‑2/Bax pathway.
authors: Department of Cardiology, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
authors: Yiping
authors: Y
authors: Wang
authors: Department of Cardiology, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
authors: Zhaohui
authors: Z
authors: Hu
authors: Department of Cardiology, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
authors: Bing
authors: B
authors: Sun
authors: Department of Cardiology, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
authors: Jiahong
authors: J
authors: Xu
authors: Department of Cardiology, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
authors: Jinfa
authors: J
authors: Jiang
authors: Department of Cardiology, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
authors: Ming
authors: M
authors: Luo
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000097:blood; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D036145:Ginsenosides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C097367:ginsenoside Rg3; D007770:L-Lactate Dehydrogenase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase; D053148:Caspase 3; D053453:Caspase 9