Abstract

As a major ingredient of Radix ginseng, ginsenoside Rg1 (Rg1) has been increasingly recognized to benefit the heart condition, however, the rationale behind the role is not fully understood. In vitro study in H9c2 cardiomyocytes has shown the potential of Rg1 to increase ATP content in the cells. We thus speculated that the protective effect of Rg1 on heart ischemia and reperfusion (I/R) injury implicates energy metabolism regulation. The present study was designed to verify this speculation. Male Sprague-Dawley rats were subjected to 30 min of occlusion of left coronary anterior descending artery followed by reperfusion for 90 min. Rg1 (5 mg/kg/h) was continuously administrated intravenously 30 min before occlusion until the end of reperfusion. Myocradial blood flow and heart function were monitored over the period of I/R. Myocardial infarct size, structure and apoptosis, energy metabolism, and change in RhoA signaling pathway were evaluated 90 min after reperfusion. Binding of Rg1 to RhoA was assessed using Surface Plasmon Resonance (SPR). Rg1 prevented I/R-elicited insults in myocardium, including myocardial infarction and apoptosis, decreased myocardial blood flow (MBF) and heart function, and alteration in myocardium structure. Rg1 restored the production of ATP in myocardium after I/R. Rg1 was able to bind to RhoA and down-regulate the activity of RhoA signaling pathway. These results indicated that Rg1 had protective potential against I/R-induced myocardial injury, which may be related to inhibiting myocardial apoptosis and modulating energy metabolism through binding to RhoA.

Highlights

  • Ischemic heart disease (IHD) is the leading cause of death and disability worldwide

  • The quantitative analysis of area at risk (AAR)/left ventricle (LV) and infarct area/AAR depicted in Figures 1B,C showed a significant increase in AAR/LV and infarct area/AAR in ischemia and reperfusion (I/R) group compared with Sham group

  • The evidence from the present study highly suggests that the cardioprotective effect of Ginsenoside Rg1 (Rg1) is mediated by a mechanism involving modulation of energy metabolism enhancing activity and expression of mitochondria respiratory chain Complexes via RhoA/Rho-associated Coiled-coil Containing Protein Kinase (ROCK) signaling pathway

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Summary

Introduction

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Until now, the most effective strategy for IHD is timely percutaneous coronary intervention (PCI). Ischemia halts oxidative phosphorylation in mitochondria, decreases the activity, and/or impairs the expression of respiratory chain complexes (He et al, 2014; Mu et al, 2015; Yang et al, 2015), leading to decrease in ATP synthesis and ATP deprivation (Burwell et al, 2009; Wheaton and Chandel, 2011; Mu et al, 2015; Yang et al, 2015). Mitochondria malfunction initiates apoptosis, which, along with ROS, exaggerates the energy depletion-caused myocardial injury (Pell et al, 2016; Han et al, 2017). The regime for this purpose is limited at present

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