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

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.

• Authors: Xia Gong, Li Zhang, Rong Jiang, Chang-Dong Wang, Xin-Ru Yin, Jing-Yuan Wan
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 34 Issue 3 Pg. 265-71 (Mar 2014) ISSN: 1099-1263 [Electronic] England
• PMID: 23620140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 John Wiley & Sons, Ltd.

Chemical References

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

Topics

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