Exploring the mechanism of Shengmai Yin for coronary heart disease based on systematic pharmacology and chemoinformatics

Biosci Rep. 2020 Jun 26;40(6):BSR20200286. doi: 10.1042/BSR20200286.

Abstract

Objective: To explore the mechanism of Shengmai Yin (SMY) for coronary heart disease (CHD) by systemic pharmacology and chemoinformatics.

Methods: Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), traditional Chinese medicine integrative database (TCMID) and the traditional Chinese medicine (TCM) Database@Taiwan were used to screen and predict the bioactive components of SMY. Pharmmapper were utilized to predict the potential targets of SMY, the TCMSP was utilized to obtain the known targets of SMY. The Genecards and OMIM database were utilized to collect CHD genes. Cytoscape was then used for network construction and analysis, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. After that, animal experiments were then performed to further validate the results of systemic pharmacology and chemoinformatics.

Results: Three major networks were constructed: (1) CHD genes' protein-protein interaction (PPI) network; (2) SMY-CHD PPI network; (3) SMY known target-CHD PPI network. The other networks are minor networks generated by analyzing the three major networks. Experimental results showed that compared with the model group, the Shengmai injection (SMI) can reduce the myocardial injury score and the activities of serum aspartate aminoconvertase (AST), CK and lactate dehydrogenase (LDH) in rats (P<0.05), and reduce serum lipid peroxide (LPO) content and increase serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in myocardial infarction rats (P<0.05). SMI can also decrease the expression of MMP-9 mRNA and increase that of TIMP-1 mRNA (P<0.01).

Conclusion: SMY may regulate the signaling pathways (such as PPAR, FoxO, VEGF signaling), biological processes (such as angiogenesis, blood pressure formation, inflammatory response) and targets (such as AKT1, EGFR, MAPK1) so as to play a therapeutic role in CHD.

Keywords: Chemoinformatics; Chinese medicine; Coronary heart disease; Shengmai Injection; Shengmai Yin; Systematic pharmacology.

MeSH terms

  • Animals
  • Cardiovascular Agents / pharmacology*
  • Coronary Disease / drug therapy*
  • Coronary Disease / genetics
  • Coronary Disease / metabolism
  • Coronary Disease / physiopathology
  • Databases, Factual
  • Disease Models, Animal
  • Drug Combinations
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Gene Regulatory Networks
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Protein Interaction Maps
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism

Substances

  • Cardiovascular Agents
  • Drug Combinations
  • Drugs, Chinese Herbal
  • Timp1 protein, mouse
  • Tissue Inhibitor of Metalloproteinase-1
  • fructus schizandrae, radix ginseng, radix ophiopogonis drug combination
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat