Exploring the mechanism of Tingli Pill in the treatment of HFpEF based on network pharmacology and molecular docking

Abstract

To explore the mechanism of action of Tingli Pill (TLP) in the treatment of heart failure with preserved ejection fraction (HFpEF) by using network pharmacology and molecular docking technology. The active components and targets of TLP were screened using the TCMSP and UniProt databases. HFpEF-related targets were identified using the OMIM and GeneCards databases. Drug-disease intersection targets were obtained via Venny 2.1.0, as well as establishing the "component-target" network and screening out the core active components. Construct a protein-protein interaction network of intersecting targets using the STRING database as well as Cytoscape software and filter the core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of core targets were performed using the Metascape database. The core active components of TLP for HFpEF were quercetin, kaempferol, β-sitosterol, isorhamnetin and hederagenin. The core targets of TLP for HFpEF were JUN, MAPK1, TP53, AKT1, RELA, TNF, MAPK14, and IL16. Gene ontology enrichment analysis obtained 1528 biological processes, 85 cell components, and 140 molecular functions. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 1940 signaling pathways, mainly involved in lipid and atherosclerosis, regulation of apoptotic signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, oxidative stress, TNF signaling pathway, and IL-17 signaling pathway. TLP has the characteristics of multi-component, multi-target, and multi-pathway in the treatment of HFpEF. This study lays the foundation for revealing the pharmacodynamic substances and mechanism of TLP in the treatment of HFpEF.

Figure 1.

Flow chart of the pharmacology study on TLP treatment for HFpEF. HFpEF = heart failure with preserved ejection fraction, TLP = Tingli Pill.

Figure 2.

Venn diagram of the intersection target of TLP and HFpEF (A). Component-target network (B). HFpEF = heart failure with preserved ejection fraction, TLP = Tingli Pill.

Figure 3.

PPI diagram (A); Hub gene (B); and gene cluster analysis (C). PPI = protein–protein interaction.

Figure 4.

GO enrichment analysis (A); and KEGG enrichment analysis (B). BP = biological process, CC = cellular component, GO = gene ontology, KEGG = Kyoto Encyclopedia of Genes and Genomes, MF = molecular function.

Figure 5.

Molecular docking map.