Cardamonin protects septic mice from acute lung injury by preventing endothelial barrier dysfunction

J Biochem Mol Toxicol. 2012 Jul;26(7):282-90. doi: 10.1002/jbt.21420. Epub 2012 Jun 13.

Abstract

Cardamonin, a flavone compound isolated from Alpinia katsumadai Heyata seeds, has been reported to possess anti-inflammatory and anticoagulative activities, and it might be beneficial for management of sepsis. This study was conducted to examine the protective effects of cardamonin on experimental sepsis and resultant acute lung injury (ALI). Cardamonin (30 and 100 mg/kg) significantly elevated the survival rate of septic mice, alleviated ALI and lung microvascular leak, and lowered the serum levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6. In vitro, it (25 and 50 µM) concentration dependently inhibited endothelium permeability and downregulated phosphorylation of P38 in rat lung microvascular endothelial cells induced by lipopolysaccharide (LPS). P38 inhibitor inhibited the endothelium permeability. In RAW 264.7 macrophage cells, cardamonin also showed selective inhibition of P38 phosphorylation induced by LPS. These results indicate that cardamonin can protect septic mice from ALI by preventing endothelium barrier dysfunction via selectively inhibiting P38 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / etiology
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / physiopathology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Cells, Cultured
  • Chalcones / administration & dosage*
  • Endothelial Cells / drug effects
  • Endothelial Cells / pathology
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Lipopolysaccharides / toxicity
  • Mice
  • Permeability / drug effects
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / chemically induced
  • Sepsis / complications
  • Sepsis / physiopathology
  • Tumor Necrosis Factor-alpha / blood
  • p38 Mitogen-Activated Protein Kinases* / metabolism

Substances

  • Chalcones
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases
  • cardamonin