Ginsenoside Rb3 protects cardiomyocytes against ischemia-reperfusion injury via the inhibition of JNK-mediated NF-κB pathway: a mouse cardiomyocyte model.

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.

• Authors: Lijia Ma, Huimin Liu, Zulong Xie, Shuang Yang, Wei Xu, Jingbo Hou, Bo Yu
• Journal: PloS one (PLoS One) Vol. 9 Issue 8 Pg. e103628 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25084093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ginsenosides
• NF-kappa B
• ginsenoside Rb3
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Cell Line
• Electrophoretic Mobility Shift Assay
• Enzyme-Linked Immunosorbent Assay
• Ginsenosides (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Microscopy, Fluorescence
• Myocytes, Cardiac (drug effects, metabolism)
• NF-kappa B (metabolism)
• Real-Time Polymerase Chain Reaction
• Reperfusion Injury (metabolism)
• Signal Transduction (drug effects)