Leonurine protects against tumor necrosis factor-α-mediated inflammation in human umbilical vein endothelial cells

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)-alpha-induced human umbilical vein endothelial cells (HUVEC) activation and the underlying molecular mechanisms. Methods: Mitogen-activated protein kinases (MAPK) activation, nuclear factor-kappa B (NF-kappa B) activation, and inflammatory mediators expression were detected by Western blot or enzyme-liked immunosorbent assay, intracellular reactive oxygen species (ROS) and NF-kappa B p65 translocation were measured by immunofluorescence, endothelial cell-monocyte interaction was detected by microscope. Results: Leonurine inhibited U937 cells adhesion to TNF-alpha-activated HUVEC in a concentration dependent manner. Treatment with leonurine blocked TNF-alpha-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-alpha-induced intracellular ROS production in HUVEC. Furthermore, leonurine also suppressed the TNF-alpha-activated p38 phosphorylation and I kappa B alpha degradation. Subsequently, reduced NF-kappa B 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-kappa B activation, which may have a potential therapeutic use for inflammatory vascular diseases. (C) 2011 Elsevier Ireland Ltd. All rights reserved.