Jiang Zhi Granule protects immunological barrier of intestinal mucosa in rats with non-alcoholic steatohepatitis

Pharm Biol. 2021 Dec;59(1):1359-1368. doi: 10.1080/13880209.2021.1979594.

Abstract

Context: Jiang Zhi Granule (JZG) is known to improve hepatic function, reduce liver fat deposition and inflammation in non-alcoholic fatty liver disease (NAFLD).

Objective: To determine the protective mechanism of JZG on immunological barrier of intestinal mucosa in rats with diet-induced non-alcoholic steatohepatitis (NASH).

Materials and methods: A Sprague-Dawley (SD) model of NASH was established using a high-fat diet and 1% dextran sulphate sodium (DSS) through drinking water. The rats were randomized into four groups and treated for four weeks, respectively, including normal control (NC), model control (MC), positive control (PC) and JZG. Mesenteric lymph nodes (MLNs) cells were isolated and cultured to assess a potential disruption of the enteric immune barrier. Also, investigation of intestinal mucosal dendritic cell-toll-like-receptor-myeloid differentiation primary response 88 (DC-TLR-MyD88) signalling pathway in vitro was examined.

Results: The lethal concentration 50 (LD50) of JZG was greater than 5 g/kg, while its inhibitory concentration 50 (IC50) was 1359 μg/mL in HepG2. In JZG group, the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), malondialdehyde (MDA), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and serum endotoxin were significantly (p < 0.01) reduced. In contrast, plasma concentrations of high-density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD) were increased. Furthermore, proinflammatory factor, interferon-γ (IFN-γ)+ from CD4+ T cells in DSS-induced NASH rats increased significantly (p < 0.01) compared to NC group. Importantly, JZG treatment substantially decreased (p < 0.01) the relative expressions of TLR-44 and MyD88.

Conclusions: JZG treatment may protect immunological barrier of intestinal mucosa in NASH individual.

Keywords: DSS; MLNs; TLR4–MyD88.

MeSH terms

  • Animals
  • Dextran Sulfate
  • Diet, High-Fat
  • Disease Models, Animal
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / toxicity
  • Female
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Lethal Dose 50
  • Male
  • Myeloid Differentiation Factor 88 / genetics
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 4 / genetics

Substances

  • Drugs, Chinese Herbal
  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • jiangzhi
  • Dextran Sulfate

Grants and funding

This work was supported by Shanghai Natural Science Foundation of China (Grant No. 17ZR1431000), Shanghai Pudong New Area Health Committee Joint Tackling Project (Grant No. PW2016D-8) and Longhua Medical Scholar (LYTD-40), Pudong famous traditional Chinese medicine training plan (PWRzm2020-03) and Plan for reserve talents of traditional Chinese medicine of Shanghai University of Traditional Chinese Medicine (2020).