Hepatoprotective effects of syringin on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice

J Appl Toxicol. 2014 Mar;34(3):265-71. doi: 10.1002/jat.2876. Epub 2013 Apr 26.

Abstract

The prognosis for fulminant hepatic failure (FHF) still remains extremely poor with a high mortality and, therefore, better treatments are urgently needed. Syringin, a main active substance isolated from Eleutherococcus senticosus, has been reported to exhibit immunomodulatory and anti-inflammatory properties. In this study, we investigated the effects and underlying mechanisms of syringin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced FHF in mice. Mice were administered syringin (10, 30 and 100 mg kg(-1), respectively) intraperitoneally (i.p) 30 min before LPS/D-GalN then mortality and liver injury were evaluated subsequently. We found that syringin dose-dependently attenuated LPS/D-GalN-induced FHF, as indicated by reduced mortality, inhibited aminotransferase and malondialdehyde (MDA) content, an increased glutathione (GSH) concentration and alleviated pathological liver injury. In addition, syringin inhibited LPS/D-GalN-induced hepatic caspase-3 activation and hepatocellular apoptosis, myeloperoxidase (MPO) activity and intercellular adhesion molecule-1 (ICAM-1) expression, as well as hepatic tissues tumor necrosis factor-alpha (TNF-α) production and NF-κB activation in a dose-dependent manner. These experimental data indicate that syringin might alleviate the FHF induced by LPS/D-GalN through inhibiting NF-κB activation to reduce TNF-α production.

Keywords: TNF-α; apoptosis; fulminant hepatic failure; lipopolysaccharide; syringin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Eleutherococcus / chemistry
  • Galactosamine / toxicity*
  • Glucosides / administration & dosage
  • Glucosides / isolation & purification
  • Glucosides / therapeutic use*
  • Lipopolysaccharides / toxicity*
  • Liver Failure, Acute / etiology
  • Liver Failure, Acute / pathology
  • Liver Failure, Acute / prevention & control*
  • Liver Function Tests
  • Mice
  • Mice, Inbred BALB C
  • Phenylpropionates / administration & dosage
  • Phenylpropionates / isolation & purification
  • Phenylpropionates / therapeutic use*
  • Protective Agents / administration & dosage
  • Protective Agents / isolation & purification
  • Protective Agents / therapeutic use*
  • Survival Analysis

Substances

  • Glucosides
  • Lipopolysaccharides
  • Phenylpropionates
  • Protective Agents
  • lipopolysaccharide, Escherichia coli O111 B4
  • Galactosamine
  • syringin