Application of Network Pharmacology to Explore the Mechanism of Yi Xin Tai Formula in Treating Heart Failure

Abstract

Objective: To explore the possible mechanism of Yi Xin Tai Formula (YXTF) in treating heart failure (HF) by network pharmacology method and to verify the related targets by western blotting. Methods: Using the traditional Chinese medicine systems pharmacology (TCMSP) database with its analysis platform for HF as a disease model, the active ingredients of YXTF were filtered according to the oral bioavailability (OB) and drug- likeness (DL), and the corresponding targets were predicted. The disease targets of HF were retrieved by Human Phenotype Ontology (HPO) database. Then, “YXTF compounds - Targets - HF” network was constructed in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, the network visualized through the Cytoscape software, and the key nodes of the network achieved according to Degree (D), Closeness Centrality (CC), and Betweenness Centrality (BC). Kyoto Encyclopedia of Genes and Genomes (KEGG) gene function enrichment analysis was carried out for the key nodes with the help of GATHER database platform. The rabbit model of HF was established by coarctation of the abdominal aorta and perfusion of propylthiouracil (PTU). The pathological changes and protein expression of transforming growth factor beta (TGF-β) protein were observed by western blotting. Results: “YXTF compounds - Targets - HF” network consisted of 403 nodes, 136 key nodes and 10 related KEGG pathways that included focal adhesions, cell cycles, mitogen-activated protein kinase (MAPK) signaling pathways, Toll-like receptor signaling pathways, Cytokine-cytokine receptor interactions, Gap junctions, adherens junctions, TGF-β signaling pathways, apoptosis and Wnt signaling pathways, respectively. The expression of TGF-β protein in myocardium decreased significantly. Conclusions: According to the network pharmacology, the treatment of YXTF for HF might be related to 10 metabolic pathways. The effects of the multicompound-multitarget-multi pathways and the synergistic effect drawn from the compounds that act as the monarch, minister, adjuvant, guide medicines were revealed through this study. Keywords: Yi Xin Tai Formula (YXTF), Heart failure (HF), Network pharmacology, Western blotting, TGF-β signal pathway