Wogonoside inhibits lipopolysaccharide-induced angiogenesis in vitro and in vivo via toll-like receptor 4 signal transduction

Toxicology. 2009 May 2;259(1-2):10-7. doi: 10.1016/j.tox.2009.01.010. Epub 2009 Jan 20.

Abstract

Wogonoside, one flavonoid derived from the root of Scutellaria baicalensis Georgi, has been reported for its anti-inflammation activity; however, whether it can inhibit inflammation-induced angiogenesis is still unclear. In the present study, we evaluated the effect of wogonoside on lipopolysaccharide (LPS)-induced angiogenesis in vitro and in vivo. Wogonoside suppressed the LPS-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs), as well as microvessel sprouting from rat aortic rings in vitro. Moreover, wogonoside also inhibited LPS-stimulated vessel growth of Chicken chorioallantoic membrane (CAM) in vivo. The mechanism revealed that wogonoside inhibited LPS-induced toll-like receptor 4 (TLR4) up-regulation and its downstream mitogen-activated protein kinases (MAPKs) activation, by decreasing the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase. The results suggest that wogonoside inhibits LPS-induced angiogenesis both in vitro and in vivo, and that it might have a therapeutic potential for the diseases associated with the development of both inflammation and angiogenesis progress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Cells, Cultured
  • Chick Embryo
  • Chorioallantoic Membrane
  • Extracellular Signal-Regulated MAP Kinases / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavanones / pharmacology*
  • Glucosides / pharmacology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / toxicity
  • Male
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / drug effects*
  • Toll-Like Receptor 4 / metabolism
  • Umbilical Veins / drug effects
  • Umbilical Veins / metabolism
  • Up-Regulation / drug effects
  • p38 Mitogen-Activated Protein Kinases / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Flavanones
  • Glucosides
  • Lipopolysaccharides
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • wogonoside