Protective Effects of Rhodiola Crenulata Extract on Hypoxia-Induced Endothelial Damage via Regulation of AMPK and ERK Pathways

Int J Mol Sci. 2018 Aug 3;19(8):2286. doi: 10.3390/ijms19082286.

Abstract

Rhodiola crenulata root extract (RCE) has been shown to possess protective activities against hypoxia both in vitro and in vivo. However, the effects of RCE on response to hypoxia in the endothelium remain unclear. In this study, we aimed to examine the effects of RCE in endothelial cells challenged with hypoxic exposure and to elucidate the underlying mechanisms. Human umbilical vein endothelial cells were pretreated with or without RCE and then exposed to hypoxia (1% O₂) for 24 h. Cell viability, nitric oxide (NO) production, oxidative stress markers, as well as mechanistic readouts were studied. We found that hypoxia-induced cell death, impaired NO production, and oxidative stress. These responses were significantly attenuated by RCE treatment and were associated with the activation of AMP-activated kinase and extracellular signal-regulated kinase 1/2 signaling pathways. In summary, we showed that RCE protected endothelial cells from hypoxic insult and suggested that R. crenulata might be useful for the prevention of hypoxia-associated vascular dysfunction.

Keywords: AMPK; ERK; Rhodiola crenulata; endothelial NOS; endothelial cell; hypoxia.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Cell Hypoxia / drug effects*
  • Cell Survival / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology*
  • Rhodiola / chemistry*
  • Signal Transduction / drug effects

Substances

  • Plant Extracts
  • AMP-Activated Protein Kinases