Rhodiola crenulata Attenuates High Glucose Induced Endothelial Dysfunction in Human Umbilical Vein Endothelial Cells

Am J Chin Med. 2017;45(6):1201-1216. doi: 10.1142/S0192415X17500665. Epub 2017 Aug 22.

Abstract

Rhodiola crenulata root extract (RCE), a traditional Chinese medicine, has been shown to regulate glucose and lipid metabolism via the AMPK pathway in high glucose (HG) conditions. However, the effect of RCE on HG-induced endothelial dysfunction remains unclear. The present study was designed to examine the effects and mechanisms of RCE against hyperglycemic insult in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without RCE and then exposed to 33[Formula: see text]mM HG medium. The cell viability, nitrite production, oxidative stress markers, and vasoactive factors, as well as the mechanisms underlying RCE action, were then investigated. We found that RCE significantly improved cell death, nitric oxide (NO) defects, and oxidative stress in HG conditions. In addition, RCE significantly decreased the HG-induced vasoactive markers, including endothelin-1 (ET-1), fibronectin, and vascular endothelial growth factor (VEGF). However, the RCE-restored AMPK-Akt-eNOS-NO axis and cell viability were abolished by the presence of an AMPK inhibitor. These findings suggested that the protective effects of RCE were associated with the AMPK-Akt-eNOS-NO signaling pathway. In conclusion, we showed that RCE protected endothelial cells from hyperglycemic insult and demonstrated its potential for use as a treatment for endothelial dysfunction in diabetes mellitus.

Keywords: AMPK; Endothelial Dysfunction; High Glucose; Rhodiola crenulata; eNOS.

MeSH terms

  • Cell Survival / drug effects
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / etiology
  • Endothelin-1 / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism*
  • Fibronectins / metabolism
  • Glucose / adverse effects*
  • Glucose / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipid Metabolism / drug effects
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Nitric Oxide / metabolism
  • Oxidative Stress
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rhodiola / chemistry*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Endothelin-1
  • Fibronectins
  • Plant Extracts
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide
  • Glucose