ABSTRACT
Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.
Subject(s)
Ginsenosides , Myocardial Reperfusion Injury , Rats , Mice , Animals , Myocardial Reperfusion Injury/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Apoptosis , Myocytes, Cardiac/metabolismABSTRACT
The COVID-19 pandemic has affected 222 countries and territories around the globe. Notably, the speed of COVID-19 spread varies significantly across countries. This cross-cultural research proposes and empirically examines how national culture influences the speed of COVID-19 spread in three studies. Study 1 examines the effects of Hofstede's national cultural dimensions on the speed of COVID-19 spread in 60 countries. Drawing on the GLOBE study (House et al., 2004), Study 2 investigates how GLOBE cultural dimensions relate to the speed of the pandemic's spread in 55 countries. Study 3 examines the effect of cultural tightness in 31 countries. We find that five national cultural dimensions - power distance, uncertainty avoidance, humane orientation, in-group collectivism, and cultural tightness - are significantly related to the speed of COVID-19 spread in the initial stages, but not in the later stages, of the pandemic. Study 1 shows that the coronavirus spreads faster in countries with small power distance and strong uncertainty avoidance. Study 2 supports these findings and further reveals that countries with low humane orientation and high in-group collectivism report a faster spread of the disease. Lastly, Study 3 shows that COVID-19 spreads slower in countries with high cultural tightness.