Lycium barbarum polysaccharide attenuates alcoholic cellular injury through TXNIP-NLRP3 inflammasome pathway

Int J Biol Macromol. 2014 Aug;69:73-8. doi: 10.1016/j.ijbiomac.2014.05.034. Epub 2014 May 22.

Abstract

Lycium barbarum has been used as a traditional Chinese medicine to nourish liver, kidneys and the eyes. However, the underlying mechanisms of its hepatic-protective properties remain uncertain. In this study, we aimed to investigate whether thioredoxin-interacting protein (TXNIP) and NOD-like receptor 3 (NLRP3) inflammasome mediated the attenuation of ethanol-induced hepatic injury by Lycium barbarum polysaccharide (LBP). Rat normal hepatocyte line BRL-3A was pre-treated with LBP prior to ethanol incubation. Hepatic damages, including apoptosis, inflammation, and oxidative stress, were measured. Then the inhibition of endogenous TXNIP expression was achieved by using its specific siRNA to test its possible involvement in the injury attenuation. We found that 50μg/ml LBP pre-treatment significantly alleviated 24-h ethanol exposure-induced overexpression of TXNIP, increased cellular apoptosis, secretion of inflammatory cytokines, activation of NLRP3 inflammasome, production of ROS, and reduced antioxidant enzyme expression. Silence of TXNIP suppressed the activated NLRP3 inflammasome, increased oxidative stress and worsened apoptosis in the cells. Further addition of LBP did not influence the effects of TXNIP inhibition on the cells. In conclusion, inhibition of hepatic TXNIP by LBP contributes to the reduction of cellular apoptosis, oxidative stress and NLRP3 inflammasome-mediated inflammation.

Keywords: LBP; NLRP3 inflammasome; TXNIP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cell Line
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology*
  • Cytoprotection / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • Ethanol / adverse effects*
  • Inflammasomes / metabolism*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Oxidative Stress / drug effects
  • Rats
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Drugs, Chinese Herbal
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Receptors, Cytoplasmic and Nuclear
  • TXNIP protein, rat
  • lycium barbarum polysaccharide
  • Ethanol