Abstract
Ginsenoside Rb3 is extracted from the plant Panax ginseng and plays important roles in cardiovascular diseases, including myocardial ischemia-reperfusion (I/R) injury. NF-κB is an important transcription factor involved in I/R injury. However, the underlying mechanism of ginsenoside Rb3 in myocardial I/R injury remains poorly understood. In the current study, a model of myocardial I/R injury was induced via oxygen and glucose deprivation (OGD) followed by reperfusion (OGD-Rep) in mouse cardiac myoblast H9c2 cells. Our data demonstrate that ginsenoside Rb3 suppresses OGD-Rep-induced cell apoptosis by the suppression of ROS generation. By detecting the NF-κB signaling pathway, we discover that the protective effect of ginsenoside Rb3 on the OGD-Rep injury is closely related to the inhibition of NF-κB activity. Ginsenoside Rb3 inhibits the upregulation of phospho-IκB-α and nuclear translocation of NF-κB subunit p65 which are induced by ORD-Rep injury. In addition, the extract also inhibits the OGD-Rep-induced increase in the expression of inflammation-related factors, such as IL-6, TNF-α, monocyte chemotactic protein-1 (MCP-1), MMP-2 and MMP-9. However, LPS treatment alleviates the protective roles of ginsenoside Rb3 and activates the NF-κB pathway. Finally, the upstream factors of NF-κB were analyzed, including the Akt/Foxo3a and MAPK signaling pathways. We find that ginsenoside Rb3 pretreatment only decreases the phosphorylation of JNK induced by OGD-Rep injury, an indicator of the MAPK pathway. Importantly, an inhibitor of phospho-JNK, SP600125, protects against OGD-Rep induced apoptosis and inhibited NF-κB signaling pathway, similar to the roles of ginsenoside Rb3. Taken together, our results demonstrate that the protective effect of ginsenoside Rb3 on the OGD-Rep injury is attributed to the inhibition of JNK-mediated NF-κB activation, suggesting that ginsenoside Rb3 has the potential to serve as a novel therapeutic agent for myocardial I/R injury.
Highlights
Ischemic myocardial disease is a complicated heart disorder worldwide, of which the main and most common cause is coronary atherosclerosis caused by stenosis or occlusion [1]
Our results demonstrate that the protective effect of ginsenoside Rb3 on the oxygen and glucose deprivation followed by reperfusion (OGDRep) injury is attributed to the inhibition of Jun NH(2)terminal kinase (JNK)-mediated NF-kB activation, suggesting that ginsenoside Rb3 has the potential to serve as a novel therapeutic agent for myocardial I/R injury
Because I/R injury results in cell apoptosis, we aimed to determine the roles of ginsenoside Rb3 in this process
Summary
Ischemic myocardial disease is a complicated heart disorder worldwide, of which the main and most common cause is coronary atherosclerosis caused by stenosis or occlusion [1]. It is characterized by the decreased blood flow to the myocardium, resulting in the deficient supply of glucose, oxygen and other nutrients that are essential to generate energy. The perfusion of the ischemic myocardium is a crucial therapeutic strategy to alleviate ischemic symptoms [2]. The inhibition of MMPs or pro-inflammatory cytokines may be novel therapeutic strategy for myocardial I/R injury
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