Lycium barbarum polysaccharides improve hepatic injury through NFkappa-B and NLRP3/6 pathways in a methionine choline deficient diet steatohepatitis mouse model

Int J Biol Macromol. 2018 Dec;120(Pt B):1480-1489. doi: 10.1016/j.ijbiomac.2018.09.151. Epub 2018 Sep 25.

Abstract

Lycium barbarum polysaccharides (LBP) are major bioactive constituents of wolfberry which possess several pharmacological effects such as antioxidant and immunomodulatory activities. We aimed to evaluate how LBP attenuated the hepatic injury in a non-alcoholic steatohepatitis (NASH) methionine-choline deficient (MCD) mouse model. NASH was induced in C57BL/6N mice by feeding with MCD diet for 6 weeks. During the experiments, 1 mg/kg LBP was intragastrically fed on a daily basis with or without MCD diet lasting from the 4th to 6th week. Control and vehicle-control (LBP + PBS) were fed with a regular animal chow. LBP significantly ameliorated NASH-induced injuries, including the increase of serum ALT and AST levels, hepatic oxidative stress, fibrosis, inflammation, and apoptosis. The hepatoprotective effects of LBP were accompanied by the attenuation of thioredoxin interacting protein, nod-like receptor protein 3/6 (NLRP3/6) and reduced NF-κB (nuclear factor-kappa B) activity. Vehicle LBP fed mice showed no adverse effect on the liver. In conclusion, the suppression of the NLRP3/6 inflammasome pathway and NF-κB activation may partly contribute to the reduction of the hepatic injury during the progression of NASH by therapeutic LBP treatment.

Keywords: Lycium barbarum polysaccharides; Methionine-choline deficient diet; Non-alcoholic steatohepatitis.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Choline / analysis
  • Diet / adverse effects*
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Fibrosis
  • Liver / drug effects*
  • Liver / injuries
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Methionine / analysis
  • Mice
  • NF-kappa B / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Oxidative Stress / drug effects
  • Receptors, Cell Surface / metabolism*

Substances

  • Antioxidants
  • Drugs, Chinese Herbal
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nod-like receptor pyrin domain-containing protein 6, mouse
  • Receptors, Cell Surface
  • lycium barbarum polysaccharide
  • Methionine
  • Choline