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.
Wenwen Zhao  1 ,  Meng Xiao  1 ,  Jie Yang  2 ,  Li Zhang  3 ,  Yinying Ba  1 ,  Rongrong Xu  1 ,  Zongyang Liu  1 ,  Haiyan Zou  1 ,  Ping Yu  1 ,  Xia Wu  4 ,  Xiaoqing Chen  5
Affiliations
  • 1. School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
  • 2. Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, China.
  • 3. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 4. School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China. Electronic address: [email protected].
  • 5. School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China. Electronic address: [email protected].
PMID: 31387054 DOI: 10.1016/j.phymed.2019.153039
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.
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