Investigating the Mechanisms of Action of Depside Salt from Salvia miltiorrhiza Using Bioinformatic Analysis

Abstract

Salvia miltiorrhiza is a traditional Chinese medicinal herb used for treating cardiovascular diseases. Depside salt from S. miltiorrhiza (DSSM) contains the following active components: magnesium lithospermate B, lithospermic acid, and rosmarinic acid. This study aimed to reveal the mechanisms of action of DSSM. After searching for DSSM-associated genes in GeneCards, Search Tool for Interacting Chemicals, SuperTarget, PubChem, and Comparative Toxicogenomics Database, they were subjected to enrichment analysis using Multifaceted Analysis Tool for Human Transcriptome. A protein-protein interaction (PPI) network was visualised; module analysis was conducted using the Cytoscape software. Finally, a transcriptional regulatory network was constructed using the TRRUST database and Cytoscape. Seventy-three DSSM-associated genes were identified. JUN, TNF, NFKB1, and FOS were hub nodes in the PPI network. Modules 1 and 2 were identified from the PPI network, with pathway enrichment analysis, showing that the presence of NFKB1 and BCL2 in module 1 was indicative of a particular association with the NF-B signalling pathway. JUN, TNF, NFKB1, FOS, and BCL2 exhibited notable interactions among themselves in the PPI network. Several regulatory relationships (such as JUN → TNF/FOS, FOS → NFKB1 and NFKB1 → BCL2/TNF) were also found in the regulatory network. Thus, DSSM exerts effects against cardiovascular diseases by targeting JUN, TNF, NFKB1, FOS, and BCL2.