Persicarin is anti-inflammatory mediator against HMGB1-induced inflammatory responses in HUVECs and in CLP-induced sepsis mice

J Cell Physiol. 2013 Apr;228(4):696-703. doi: 10.1002/jcp.24214.

Abstract

High mobility group box 1 (HMGB1) protein is a crucial nuclear cytokine that mediates inflammatory responses, whereas persicarin is an active compound from Oenanthe javanica that has been widely researched for its neuroprotective and antioxidant activities. However, little is known of the effects of persicarin on HMGB1-mediated inflammatory response. Here, we investigated this issue by monitoring the effects of persicarin on the lipopolysaccharide (LPS) and on the cecal ligation and puncture (CLP)-mediated releases of HMGB1 and the effects of persicarin on the HMGB1-mediated modulation of inflammatory response. Persicarin potently inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells, and inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. Furthermore, persicarin reduced CLP-induced HMGB1 release and sepsis-related mortality. Given these results, persicarin should be viewed as a candidate therapeutic for the treatment of severe vascular inflammatory diseases, such as, sepsis or septic shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cecum / drug effects
  • Cecum / metabolism
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Flavones / pharmacology*
  • HMGB1 Protein / metabolism*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Ligation / methods
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Punctures / methods
  • Sepsis / drug therapy*
  • Sepsis / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Flavones
  • HMGB1 Protein
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • persicarin