iTRAQ-based quantitative proteomics and target-fishing strategies reveal molecular signatures on vasodilation of Compound Danshen Dripping Pills

Chem Biol Interact. 2020 Jan 25:316:108923. doi: 10.1016/j.cbi.2019.108923. Epub 2019 Dec 12.

Abstract

Angina pectoris can be used as an early warning for coronary artery disease. Vasodilation is an important mechanism of angina pectoris. Traditional Chinese medicine - Compound Danshen Dripping Pill (CDDP) is widely used to improve the symptoms of cardiovascular diseases (CVDs). To investigate the influence of vasodilation effect and underlying mechanisms of CDDP, we determined the vasodilation effect of thoracic aorta ring on rat induced by norepinephrine (NE). Then targets-fishing method was used to predict the potential mechanism of CDDP on vasodilation, based on the structures of the main components. Then, iTRAQ-based quantitative proteomics analysis was used for verification of the candidate target proteins and pathways to illustrate the underlying mechanisms. Furthermore, the differentially expressed proteins in the enriched pathways were validated by western blotting. In this study, we found that CDDP could significantly inhibit NE induced aortic contraction tension, and the mechanism may be related to platelet activation, cGMP - PKG signaling pathway and vascular smooth muscle contraction. The method provides a new way to uncover the vasodilation mechanism of CDDP, as well as other multi-component herbal medicines.

Keywords: Compound Danshen Dripping Pill; Target protein; Vasodilation; iTRAQ.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Camphanes
  • Cyclic GMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Male
  • Medicine, Chinese Traditional
  • Muscle Contraction / drug effects
  • Norepinephrine / pharmacology
  • Panax notoginseng
  • Proteome / analysis*
  • Proteome / drug effects
  • Proteome / metabolism
  • Proteomics*
  • Rats
  • Rats, Sprague-Dawley
  • Salvia miltiorrhiza
  • Signal Transduction / drug effects
  • Vasodilator Agents / pharmacology*

Substances

  • Camphanes
  • Drugs, Chinese Herbal
  • Proteome
  • Vasodilator Agents
  • danshen dripping pill
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP
  • Norepinephrine