Leonurine Protects Against Tumor Necrosis factor-α-mediated Inflammation in Human Umbilical Vein Endothelial Cells

Atherosclerosis. 2012 May;222(1):34-42. doi: 10.1016/j.atherosclerosis.2011.04.027. Epub 2011 May 5.

Abstract

Objective: Leonurine, a bioactive alkaloid compound in Herba leonuri, has various pharmacological activities, including antioxidant and anti-apoptotic capacities. This study was conducted to test the hypothesis that leonurine was able to attenuate tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVEC) activation and the underlying molecular mechanisms.

Methods: Mitogen-activated protein kinases (MAPK) activation, nuclear factor-κB (NF-κB) activation, and inflammatory mediators expression were detected by Western blot or enzyme-liked immunosorbent assay, intracellular reactive oxygen species (ROS) and NF-κB p65 translocation were measured by immunofluorescence, endothelial cell-monocyte interaction was detected by microscope.

Results: Leonurine inhibited U937 cells adhesion to TNF-α-activated HUVEC in a concentration dependent manner. Treatment with leonurine blocked TNF-α-induced mRNA and protein expression of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), cyclooxygenase-2, and monocyte chemoattractant protein-1 in endothelial cells. In addition, leonurine attenuated TNF-α-induced intracellular ROS production in HUVEC. Furthermore, leonurine also suppressed the TNF-α-activated p38 phosphorylation and IκBα degradation. Subsequently, reduced NF-κB p65 phosphorylation, nuclear translocation, and DNA-binding activity were also observed.

Conclusions: Our results demonstrated for the first time that the anti-inflammatory properties of leonurine in endothelial cells, at least in part, through suppression of NF-κB activation, which may have a potential therapeutic use for inflammatory vascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Chemokine CCL2 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • I-kappa B Kinase / metabolism
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • NF-kappa B / metabolism
  • Reactive Oxygen Species / metabolism
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / immunology
  • U937 Cells
  • Vascular Cell Adhesion Molecule-1 / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Chemokine CCL2
  • NF-kappa B
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • leonurine
  • Intercellular Adhesion Molecule-1
  • Gallic Acid
  • Cyclooxygenase 2
  • I-kappa B Kinase
  • p38 Mitogen-Activated Protein Kinases