Exploring the Potential Mechanism of Danshen in the Treatment of Concurrent Ischemic Heart Disease and Depression Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

Objective: This study aimed to explore the potential targets and mechanism of action of Danshen in treating concurrent ischemic heart disease (IHD) and depression using network pharmacology, molecular docking, and molecular dynamics simulation (MDS). Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to obtain active ingredients and targets of Danshen. Candidate targets for IHD and depression were obtained from the Genecards and DisGeNet databases. The protein–protein interaction (PPI) network was constructed using the STRING database and the Cytoscape 3.8.2 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Metascape database and the GlueGO package of the Cytoscape 3.8.2 software. Molecular docking was performed using Autodock 1.5.6 and Vina, and the MDS was completed using GROMACS 5.1.2. Results: We obtained 65 active ingredients of Danshen with 131 candidate targets and 39 intersection targets of the active ingredients and diseases. Luteolin, tanshinone IIA, and salviolone were the core active ingredients, and AKT1, TNF, IL-6, MMP9, CASP3, IL-10, PTGS2, STAT3, PPARG, IL-4, EGFR, MAPK14, NOS3, and EDN1 were the core targets. The GO and KEGG pathway enrichment analyses revealed that the intersection targets were mainly enriched in positive regulation of protein phosphorylation, blood circulation, IL-17 signaling pathway, VEGF signaling pathway, and JAK/STAT signaling pathway. The molecular docking revealed that the core active ingredients had a good affinity for the core targets. The results of MDS revealed that the protein-ligand complexes were stable. Conclusions: This study used network pharmacology to analyze the potential mechanism of action of Danshen in the treatment of concurrent IHD and depression. Additionally, the study provided a theoretical basis for further studying the pharmacological mechanisms and targets of Danshen.