Integrated Metabolomics and Network Pharmacology to Reveal the Mechanisms of Guizhi-Fuling Treatment for Myocardial Ischemia

Myocardial ischemia is a cardio-physiological condition caused by a decrease in blood perfusion to the heart, resulting in reduced oxygen supply and abnormal myocardial energy metabolism. Guizhi-Fuling (GZFL)is effective in treating Myocardial ischemia. However, its mechanism of action remains unclear and requires further exploration. we hope to reveal the mechanisms of GZFL treating Myocardial ischemia by integrating metabolomics and network pharmacology. In this study, myocardial metabolomic analysis was first performed using GC-MS to discover the potential mechanism of action of GZFL on myocardial ischemia. Then, network pharmacology was used to analyze key pathways and construct a pathway-core target network. Molecular docking was used to validate core targets in network pharmacological signaling pathways. Finally, western blots were used to verify core targets of metabolomics and network pharmacology integrated pathways as well as key targets in signaling pathways. As a result, We identified 22 important biomarkers of GZFL for the treatment of myocardial ischemia. Most of these metabolites were restored by modulation after GZFL treatment. Based on the network pharmacology, we selected the top 50 core targets using degree centrality (DC). The further comprehensive analysis focused on 3 key targets, including Tyrosine hydroxylase (TH), myeloperoxidase (MPO), and phosphatidylinositol 3-kinases (PIK3CA), and their associated metabolites and pathways. Compared with the model group, the protein expression levels of TH, MPO and PIK3CA were decreased in GZFL. Therefore, the mechanism of GZFL for treating myocardial ischemia may be to inhibit myocardial inflammatory factors, reduce myocardial inflammation, and restore endothelial function, while regulating norepinephrine release and uric acid concentration.