Investigating the Mechanisms of Action of Depside Salt fromSalvia miltiorrhizaUsing Bioinformatic Analysis

Hua Li,Hongying Liu

doi:10.1155/2017/5671860

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-κB 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.

Highlights

Salvia miltiorrhiza is widely used as a traditional Chinese medicinal herb to prevent and treat vascular diseases [1, 2]
In GeneCards [12], STICH [13], SuperTarget [14], PubChem [15], and CTD [16] databases, “magnesium lithospermate B”, “lithospermic acid” and “rosmarinic acid” were used as keywords to search for genes associated with them
The magnesium lithospermate B (MLB), rosmarinic acid (RA), and lithospermic acid (LA)-associated genes were combined into a group of 73 Depside salt from S. miltiorrhiza (DSSM)-associated genes

Summary

Introduction

Salvia miltiorrhiza ( named Danshen) is widely used as a traditional Chinese medicinal herb to prevent and treat vascular diseases [1, 2]. Depside salt from S. miltiorrhiza (DSSM) is a new medicine that contains the active components magnesium lithospermate B (MLB), lithospermic acid (LA), and rosmarinic acid (RA) [3]. MLB protects against diabetic atherosclerosis by inducing the nuclear factor erythroid 2-related factor-2-antioxidant responsive element-NAD(P)H: quinone oxidoreductase-1 pathway [8]. Du et al reported that MLB can be used to treat ischaemic heart diseases as it inhibits transforming growth factor β-activated protein kinase 1binding protein 1-p38 apoptosis signalling [9]. Kim et al demonstrated that RA inhibits adriamycin-induced cardiotoxicity by suppressing reactive oxygen species generation as well as extracellular signal-regulated kinase and c-Jun Nterminal kinase (JNK) activation [10].

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