Betulin attenuates lung and liver injuries in sepsis

Int Immunopharmacol. 2016 Jan:30:50-56. doi: 10.1016/j.intimp.2015.11.028. Epub 2015 Nov 28.

Abstract

Sepsis is a complex condition with unacceptable mortality. Betulin is a natural extract with multiple bioactivities. This study aims to evaluate the potential effects of betulin on lung and liver injury in sepsis. Cecal ligation and puncture was used to establish the rat model of sepsis. A single dose of 4mg/kg or 8mg/kg betulin was injected intraperitoneally immediately after the model establishment. The survival rate was recorded every 12h for 96h. The organ injury was examined using hematoxylin and eosin staining and serum biochemical test. The levels of proinflammatory cytokines and high mobility group box 1 in the serum were measured using ELISA. Western blotting was used to detect the expression of proteins in NF-κB and MAPK signaling pathways. Betulin treatment significantly improved the survival rate of septic rats, and attenuated lung and liver injury in sepsis, including the reduction of lung wet/dry weight ratio and activities of alanine aminotransferase and aspartate aminotransferase in the serum. In addition, levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and high mobility group box 1 in the serum were also lowered by betulin treatment. Moreover, sepsis-induced activation of the NF-κB and MAPK signaling pathway was inhibited by betulin as well. Our findings demonstrate the protective effect of betulin in lung and liver injury in sepsis. This protection may be mediated by its anti-inflammatory and NF-κB and MAPK inhibitory effects.

Keywords: Betulin; Inflammation; MAPK; NF-κB; Sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Betula / immunology
  • Cecum / surgery
  • Cytokines / metabolism
  • Disease Models, Animal
  • HMGB1 Protein / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Liver / drug effects*
  • Liver / immunology
  • Liver / pathology
  • Lung / drug effects*
  • Lung / immunology
  • Lung / pathology
  • MAP Kinase Signaling System / drug effects
  • Male
  • NF-kappa B / metabolism
  • Plant Bark
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Triterpenes / administration & dosage*

Substances

  • Cytokines
  • HMGB1 Protein
  • Inflammation Mediators
  • NF-kappa B
  • Triterpenes
  • betulin
  • Aspartate Aminotransferases
  • Alanine Transaminase