Transcriptomics and metabolomics reveal the cardioprotective effect of Compound Danshen tablet on isoproterenol-induced myocardial injury in high-fat-diet fed mice

J Ethnopharmacol. 2020 Jan 10:246:112210. doi: 10.1016/j.jep.2019.112210. Epub 2019 Aug 31.

Abstract

Ethnopharmacological relevance: Compound Danshen tablet, an herbal preparation consisting of salviae miltiorrhizae, notoginseng and borneolum, is extensively employed clinically to treat angina pectoris, coronary arteriosclerosis and significantly improve microcirculation.

Aim of the study: To reveal the potential underlying cardioprotective mechanism(s) in isoproterenol-induced myocardial injury in high-fat-diet fed mice.

Materials and methods: Cardiac transcriptomics was analyzed by Illumina mRNA-Seq sequencing. The restored cardiovascular diseases (CVD)-related genes by Compound Danshen tablet were validated by quantitative real time polymerase chain reaction (qRT-PCR). Furthermore, Cardiac metabolomics were also performed using gas chromatography-mass spectrometry.

Results: From the transcriptomics study, we found the levels of 24 up-regulated and 44 down-regulated genes in the control compared to model groups. Among them, seven gene levels were restored by treatment of Compound Danshen tablet. Four CVD-related genes at the mRNA level (Sprr1a, Ppp1r3c, Bmp10 and Hspa1b) were validated successfully by qRT-PCR. From the metabolomics study, 37 differentially expressed metabolites were identified between the control and model groups. Among them, 21 metabolites were restored by treatment of Compound Danshen tablet. These altered metabolites are involved in glucose metabolism, fatty acid metabolism and amino acid metabolism.

Conclusion: These genes and metabolites might provide clues for further molecular mechanistic study of Compound Danshen tablet.

Keywords: Cardioprotective effect; Compound danshen tablet; Metabolomics; Transcriptomics.

MeSH terms

  • Animals
  • Camphanes
  • Cardiotonic Agents / pharmacology*
  • Cardiotonic Agents / therapeutic use*
  • Diet, High-Fat
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use*
  • Gene Expression Profiling
  • Heart Diseases / chemically induced
  • Heart Diseases / drug therapy
  • Heart Diseases / genetics*
  • Heart Diseases / metabolism*
  • Isoproterenol
  • Male
  • Metabolomics
  • Mice, Inbred C57BL
  • Myocardium / metabolism
  • Panax notoginseng
  • Salvia miltiorrhiza
  • Tablets
  • Transcriptome / drug effects

Substances

  • Camphanes
  • Cardiotonic Agents
  • Drugs, Chinese Herbal
  • Tablets
  • danshen dripping pill
  • Isoproterenol