Dataset Information

Ginsenoside Rg1 Ameliorates Rat Myocardial Ischemia-Reperfusion Injury by Modulating Energy Metabolism Pathways.

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.

SUBMITTER: Li L

PROVIDER: S-EPMC5808323 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ginsenoside Rg1 Ameliorates Rat Myocardial Ischemia-Reperfusion Injury by Modulating Energy Metabolism Pathways.

Li Lin L Pan Chun-Shui CS Yan Li L Cui Yuan-Chen YC Liu Yu-Ying YY Mu Hong-Na HN He Ke K Hu Bai-He BH Chang Xin X Sun Kai K Fan Jing-Yu JY Huang Li L Han Jing-Yan JY

Frontiers in physiology 20180207

As a major ingredient of <i>Radix ginseng</i>, ginsenoside Rg1 (Rg1) has been increasingly recognized to benefit the heart condition, however, the rationale behind the role is not fully understood. <i>In vitro</i> 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 s ...[more]

PMID: 29467677

Similar Datasets

Project description:ObjectiveThe incidence of acute myocardial infarction (AMI) is increasing yearly. With the use of thrombolysis or percutaneous coronary intervention (PCI), the mortality rate of acute myocardial infarction has been significantly reduced. However, reperfusion can cause additional myocardial injury. There is still a lack of effective drugs to treat I/R injury, and it is urgent to find new therapeutic drugs.MethodsIn this study, network pharmacology was used to predict potential targets and biological processes involved in Muscone-mediated treatment of acute myocardial infarction. To model ischemia‒reperfusion injury, a hypoxia-reoxygenation model and in vivo ischemia‒reperfusion injury C57BL/6 mice model was constructed. Mice were treated with Muscone i.p. for 4 weeks. We detected the cardiac function on day 28.The expression levels of the apoptotic proteins Caspase-3 and Bax and the anti-apoptotic protein Bcl-2 were detected by immunoblotting after Muscone treatment of AC16 cells and in vivo. Additionally, the gene expression levels of the PUMA and p53 were analyzed by qRT‒PCR. Molecular docking was used to evaluate the binding energy between Muscone and NLRP3-related proteins. Immunoblotting and qRT‒PCR were used to assess the expression levels of NLRP3 signaling pathway-related proteins (NLRP3, ASC, and Caspase-1) and the NLRP3 gene, respectively. Moreover, the extracellular acidification rate of AC16 cells was measured using the Seahorse system to evaluate glycolysis levels after Muscone treatment. The expression of the key glycolytic enzyme PKM2 was analyzed by immunoblotting and qRT‒PCR. Finally, ChIP‒qPCR was performed to determine the levels of histone modifications (H3K4me3, H3K27me3, and H2AK119Ub) in the PKM2 promoter region.ResultsGO functional enrichment analysis revealed that muscone was involved in regulating the biological processes (BP) of AMI, which mainly included negative regulation of the apoptosis signaling pathway, the response to lipopolysaccharide, and blood pressure regulation. The cellular components (CC) involved in muscone-mediated regulation of AMI mainly included lipid rafts, membrane microdomains, and membrane regions. The molecular functions (MF) involved in muscone-mediated regulation of AMI mainly included oxidoreductase activity, nuclear receptor activity, and transcription factor activity. In vitro results indicated that muscone treatment could inhibit the expression levels of Bax and Caspase-3 in AC16 cells after ischemia‒reperfusion while increasing the expression level of the antiapoptotic protein Bcl-2. Muscone significantly suppressed the transcription levels of p53 and PUMA in AC16 cells. Molecular docking suggested that muscone could bind well with the Cryo-EM structure of NEK7(PDB ID:6NPY). Further investigation of inflammatory pathways revealed that muscone could inhibit the expression level of NLRP3 in AC16 cells and reduce the expression levels of Caspase-1 and Caspase recruitment domain. Fluorescent quantitative PCR experiments showed that muscone significantly inhibited the transcription of NLRP3. Moreover, we found that muscone could enhance the glycolytic efficiency of AC16 cells, which may be related to the increased protein expression of PKM2 in AC16 cells. Fluorescent quantitative PCR showed that muscone could increase the transcription level of PKM2. Chromatin immunoprecipitation assays showed that muscone treatment increased the expression level of H3K4me3 in the PKM2 promoter region and inhibited the levels of H3K27me3 and H2AK119Ub in the PKM2 promoter region.ConclusionMuscone promoted myocardial glycolysis and inhibited NLRP3 pathway activation to improve myocardial ischemia‒reperfusion injury.

Dataset Information

Ginsenoside Rg1 Ameliorates Rat Myocardial Ischemia-Reperfusion Injury by Modulating Energy Metabolism Pathways.

Publications

Ginsenoside Rg1 Ameliorates Rat Myocardial Ischemia-Reperfusion Injury by Modulating Energy Metabolism Pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets