Salidroside protects cardiomyocyte against hypoxia-induced death: a HIF-1alpha-activated and VEGF-mediated pathway

Eur J Pharmacol. 2009 Apr 1;607(1-3):6-14. doi: 10.1016/j.ejphar.2009.01.046.


Cardiomyocyte death (necrosis and apoptosis) plays a critical role in the progress of heart diseases. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L, has shown cardioprotective effects in vivo. However, whether salidroside has a protective effect against cardiomyocyte death is poorly understood. The present study was aimed to investigate the cardioprotective role of salidroside and the underlying mechanisms in hypoxia-induced cardiomyocyte death. Cardiomyocytes pretreated with or without salidroside for 24 h were exposed to hypoxic condition for 6 h and then cell viability, necrosis, apoptosis, the expressions of HIF-1alpha and VEGF were investigated. Pretreatment with salidroside markedly attenuated hypoxia-induced cell viability loss, cell necrosis and apoptosis in a dose-dependent manner. Mechanistically, pretreatment with salidroside up-regulated the HIF-1alpha protein expression and induced its translocation. Moreover, the level of VEGF, a downstream target of HIF, was significantly increased in parallel with the level of HIF-1alpha following pretreatment with salidroside. However, 2-methoxyestradiol (2-ME2), a HIF-1alpha inhibitor, attenuated the protection of salidroside and blocked the increase of HIF-1alpha and VEGF. These data indicated that salidroside has protective effect against hypoxia-induced cardiomyocytes necrosis and apoptosis by increasing HIF-1alpha expression and subsequently up-regulating VEGF levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacology*
  • Cell Hypoxia
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Glucosides / administration & dosage
  • Glucosides / pharmacology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / drug effects*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Myocytes, Cardiac / pathology
  • Necrosis / pathology
  • Phenols / administration & dosage
  • Phenols / pharmacology*
  • Protein Transport / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Rhodiola / chemistry
  • Up-Regulation / drug effects
  • Vascular Endothelial Growth Factor A / drug effects*
  • Vascular Endothelial Growth Factor A / metabolism


  • Cardiotonic Agents
  • Glucosides
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Phenols
  • Vascular Endothelial Growth Factor A
  • rhodioloside