The combination of Ilexhainanoside D and ilexsaponin A1 reduces liver inflammation and improves intestinal barrier function in mice with high-fat diet-induced non-alcoholic fatty liver disease

Phytomedicine. 2019 Oct:63:153039. doi: 10.1016/j.phymed.2019.153039. Epub 2019 Jul 26.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is becoming a major health concern worldwide. Ilex hainanensis Merr. extract was proved to have anti-inflammation effect on NAFLD, and Ilexhainanoside D (IhD) and ilexsaponin A1 (IsA) were the main triterpenoid saponins extracted from it.

Purposes: To investigate the hepatoprotective effect of the combination of IhD and IsA (IIC) against NAFLD and discuss the potential mechanisms.

Methods: Male C57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD and were treated with IIC (60, 120 or 240 mg/kg) for 8 weeks. Growth parameters, abdominal fat content, serum biochemical markers, hepatic lipid accumulation and insulin tolerance were assessed. Quantitative real-time PCR was used to determine the hepatic gene expression of TLR2, TLR4, TNF-α, IL-6, and IL-1β. Western blot analysis was performed to determine the expression of the epidermal tight junction proteins ZO-1 and occludin. Gut microbiota profiles were established via high-throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene.

Results: IIC significantly reduced the severity of NAFLD induced by HFD in a dose-dependent manner. IIC decreased the ratio of Firmicutes/Bacteroidetes, reduced the relative abundance of Desulfovibrio and increased the relative abundance of Akkermansia. The intestinal barrier was improved as evidenced by the upregulation of the expression of ZO-1 and occludin in the ileum. IIC thus reduced the entry of LPS into the circulation and decreased the hepatic gene expression levels of proinflammatory cytokines.

Conclusion: This approach demonstrated the positive effects of IIC in a mouse model of NAFLD, indicating that it possibly acts by reducing inflammation and improving the intestinal barrier function.

Keywords: Gut microbiota; Ilex hainanensis; Inflammation; Intestinal barrier; Non-alcoholic fatty liver disease; Triterpenoid saponins.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Hepatitis, Animal / drug therapy
  • Heterocyclic Compounds, Bridged-Ring / administration & dosage
  • Heterocyclic Compounds, Bridged-Ring / pharmacology*
  • Intestines / drug effects
  • Male
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Protective Agents / pharmacology
  • RNA, Ribosomal, 16S
  • Saponins / administration & dosage
  • Saponins / pharmacology*
  • Triterpenes / administration & dosage
  • Triterpenes / pharmacology*
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Cytokines
  • Heterocyclic Compounds, Bridged-Ring
  • Ilexhainanoside D
  • Protective Agents
  • RNA, Ribosomal, 16S
  • Saponins
  • Tjp1 protein, mouse
  • Triterpenes
  • Zonula Occludens-1 Protein
  • ilexsaponin A1