Paeoniflorin inhibits pulmonary artery smooth muscle cells proliferation via upregulating A2B adenosine receptor in rat

PLoS One. 2013 Jul 30;8(7):e69141. doi: 10.1371/journal.pone.0069141. Print 2013.

Abstract

Paeoniflorin (PF), which is the main active ingredient in the root of Paeonia Radix, has many pharmacological effects. Here, we investigated the effect of PF on rat pulmonary artery smooth muscle cells (PASMCs) under hypoxic conditions and explored the mechanisms of the effects. The anti-proliferative effect of PF increased in a dose dependent manner. At the highest dose (20 μmol/L), the anti-proliferative effect of PF peaked at 24 h after administration. However, the selective A2B adenosine receptor (A2BAR) antagonist MRS1754 abolished it. PF increased A2BAR mRNA levels from 0.0763±0.0067 of β-actin mRNA levels (hypoxia group) to 0.1190±0.0139 (P<0.05) measured by Real Time Reverse Transcription-Polymerase Chain Reaction. A2BAR protein expression measured by Western Blot was also increased. PF inhibited the proliferation of PASMCs by blocking cell cycle progression in the S phase. These data indicated that activation of A2BAR might be involved in the anti-proliferative effect of PF on PASMCs under hypoxic conditions. The results suggested that a new mechanism of PF could be relevant to the management of clinical hypoxic pulmonary hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Agonists / chemistry
  • Adenosine A2 Receptor Agonists / pharmacology*
  • Animals
  • Benzoates / chemistry
  • Benzoates / pharmacology*
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • Glucosides / chemistry
  • Glucosides / pharmacology*
  • Hypoxia / metabolism
  • Male
  • Monoterpenes
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism*
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / metabolism*
  • Rats
  • Receptor, Adenosine A2B / genetics
  • Receptor, Adenosine A2B / metabolism*
  • Up-Regulation / drug effects

Substances

  • Adenosine A2 Receptor Agonists
  • Benzoates
  • Bridged-Ring Compounds
  • Glucosides
  • Monoterpenes
  • Receptor, Adenosine A2B
  • peoniflorin

Grants and funding

This study was supported by National Natural Science Foundation of China (No. 81270110), http://www.nsfc.gov.cn/Portal0/default152.htm Zhejiang Provincial Natural Science Foundation of China (No. Y2101208), http://www.zjnsf.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.