Cardioprotective Mechanism of Leonurine against Myocardial Ischemia through a Liver–Cardiac Crosstalk Metabolomics Study

Abstract

Leonurine has been shown to have excellent anti-myocardial ischemia effects. Our previous studies suggested that cardiac protection by leonurine during myocardial ischemia appeared to be inextricably linked to its regulation of the liver. At present, however, there are few mechanistic studies of leonurine and its regulation of hepatic metabolism against ischemic injury. In this study, a metabolomics approach was developed to give a global view of the metabolic profiles of the heart and liver during myocardial ischemia. Principal component analysis and orthogonal partial least squares discrimination analysis were applied to filter differential metabolites, and a debiased sparse partial correlation analysis was used to analyze the correlation of the differential metabolites between heart and liver. As a result, a total of thirty-one differential metabolites were identified, six in the myocardial tissue and twenty-five in the hepatic tissue, involving multiple metabolic pathways including glycine, serine and threonine, purine, fatty acid, and amino acid metabolic pathways. Correlation analysis revealed a net of these differential metabolites, suggesting an interaction between hepatic and myocardial metabolism. These results suggest that leonurine may reduce myocardial injury during myocardial ischemia by regulating the metabolism of glycine, serine and threonine, purine, fatty acids, and amino acids in the liver and heart.

Keywords

• leonurine
• metabolomics
• differential metabolites
• mechanism
• liver–cardiac crosstalk