A network pharmacology study of Chinese medicine QiShenYiQi to reveal its underlying multi-compound, multi-target, multi-pathway mode of action

PLoS One. 2014 May 9;9(5):e95004. doi: 10.1371/journal.pone.0095004. eCollection 2014.

Abstract

Chinese medicine is a complex system guided by traditional Chinese medicine (TCM) theories, which has proven to be especially effective in treating chronic and complex diseases. However, the underlying modes of action (MOA) are not always systematically investigated. Herein, a systematic study was designed to elucidate the multi-compound, multi-target and multi-pathway MOA of a Chinese medicine, QiShenYiQi (QSYQ), on myocardial infarction. QSYQ is composed of Astragalus membranaceus (Huangqi), Salvia miltiorrhiza (Danshen), Panax notoginseng (Sanqi), and Dalbergia odorifera (Jiangxiang). Male Sprague Dawley rat model of myocardial infarction were administered QSYQ intragastrically for 7 days while the control group was not treated. The differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with QSYQ, followed by constructing a cardiovascular disease (CVD)-related multilevel compound-target-pathway network connecting main compounds to those DEGs supported by literature evidences and the pathways that are functionally enriched in ArrayTrack. 55 potential targets of QSYQ were identified, of which 14 were confirmed in CVD-related literatures with experimental supporting evidences. Furthermore, three sesquiterpene components of QSYQ, Trans-nerolidol, (3S,6S,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol and (3S,6R,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol from Dalbergia odorifera T. Chen, were validated experimentally in this study. Their anti-inflammatory effects and potential targets including extracellular signal-regulated kinase-1/2, peroxisome proliferator-activated receptor-gamma and heme oxygenase-1 were identified. Finally, through a three-level compound-target-pathway network with experimental analysis, our study depicts a complex MOA of QSYQ on myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cells, Cultured
  • Drug Combinations
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Regulatory Networks / drug effects*
  • Gene Regulatory Networks / genetics
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / genetics
  • Oligonucleotide Array Sequence Analysis
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Phytotherapy / methods
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sesquiterpenes / pharmacology
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Transcriptome / drug effects*
  • Transcriptome / genetics

Substances

  • Drug Combinations
  • Drugs, Chinese Herbal
  • Lipopolysaccharides
  • Membrane Proteins
  • PPAR gamma
  • Sesquiterpenes
  • qishen yiqi
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3

Associated data

  • GEO/GSE54134

Grants and funding

This work was financially supported by the National Basic Research Program of China (no. 2012CB518405) and the National Natural Science Foundation of China (no. 81373893). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Microarray test was performed by National Engineering Center for Biochip at Shanghai by Dr. Huasheng Xiao's team.