Pro-inflammatory cytokines serve as communicating molecules between the liver and brain for hepatic encephalopathy pathogenesis and Lycium barbarum polysaccharides protection

J Ethnopharmacol. 2020 Feb 10:248:112357. doi: 10.1016/j.jep.2019.112357. Epub 2019 Nov 3.

Abstract

Ethnopharmacological relevance: Gogi berry is a traditional food supplement and medical herbal which has been widely used in Eastern Asian countries. Lycium barbarum polysaccharides (LBP) are the major active components of Gogi berry and have been proved to possess a lot of biological activities.

Aim of the study: We aimed to delineate the protective effect and mechanism of LBP on hepatic encephalopathy (HE).

Materials and methods: We investigated the protective mechanism of LBP in a thioacetamide (TAA, intraperitoneally injected, 400 mg/kg) induced acute HE mice model. Key phenotypes of clinical HE were phenocopied in the mice model, including high mortality, severe hepatic histology injury, increased hepatic oxidative stress, apoptosis, enhanced circulating levels of pro-inflammatory cytokines and ammonia, suppressed tryptophan hydroxylase activity, and deficits in locomotor activity.

Results: The pathological alterations were effectively ameliorated by the oral administration with LBP (5 mg/kg, oral gavage, everyday), which were mediated by regulating MAPK pathways in both the liver and brain. Knockout of pro-inflammatory cytokines TNF-α or IL-6 effectively ameliorated impaired mice locomotor activity and MAPK activation in the brain. In an in vitro TNF-α-, IL-6-, or ammonia-induced microglia damaged cell model, cell injuries were evidently protected by the co-administration with LBP (50 μg/ml).

Conclusion: LBP ameliorated the hepatic/brain injuries and impaired locomotor activities in a HE mice model. Pro-inflammatory cytokines may serve as communicating molecules linking the liver and brain for the HE pathogenesis, partly through MAPK regulation.

Keywords: Brain injury; Cytokine; LBP; MAPK; hepatic encephalopathy.

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cell Line
  • Cytokines / deficiency
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Fruit
  • Hepatic Encephalopathy / chemically induced
  • Hepatic Encephalopathy / metabolism
  • Hepatic Encephalopathy / pathology
  • Hepatic Encephalopathy / prevention & control*
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Locomotion / drug effects
  • Lycium* / chemistry
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Signal Transduction
  • Thioacetamide
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Inflammation Mediators
  • Interleukin-6
  • Plant Extracts
  • Polysaccharides
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Thioacetamide
  • Mitogen-Activated Protein Kinases