Leonurine attenuates lipopolysaccharide-induced inflammatory responses in human endothelial cells: involvement of reactive oxygen species and NF-κB pathways

Eur J Pharmacol. 2012 Apr 5;680(1-3):108-14. doi: 10.1016/j.ejphar.2012.01.012. Epub 2012 Jan 28.

Abstract

Leonurine, an active alkaloid of Traditional Chinese Medicine Herba leonuri, displayed cardioprotective effects by anti-oxidative and anti-apoptotic activities in vitro and in vivo. Herein, we explored the effects and possible mechanisms of leonurine on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVEC). We found that leonurine pretreatment concentration-dependently attenuated LPS-induced mRNA expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1. Meanwhile, LPS-mediated expression/release of ICAM-1, VCAM-1, and cyclooxygenase-2, and tumor necrosis factor-α was also reduced by leonurine. In addition, we confirmed that leonurine suppressed degradation of IκBα and phosphorylation of nuclear factor-κB (NF-κB) p65 as well as production of intracellular reactive oxygen species in a concentration dependent manner. Furthermore, the cytoprotective enzyme heme oxygenase-1 could be upregulated in leonurine-treated HUVEC. Our present results indicated leonurine exerted beneficial effects in inflammatory conditions partly through inhibition of reactive oxygen species and NF-κB signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • E-Selectin / genetics
  • E-Selectin / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipopolysaccharides / pharmacology*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • RNA, Messenger / genetics
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Chemokine CCL2
  • E-Selectin
  • I-kappa B Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • NFKBIA protein, human
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • leonurine
  • Intercellular Adhesion Molecule-1
  • NF-KappaB Inhibitor alpha
  • Gallic Acid
  • Heme Oxygenase-1
  • Cyclooxygenase 2
  • PTGS2 protein, human