Effect and mechanism of dihydromyricetin improving choline-deficient and L-amino acid-restricted high-fat diet-induced non-alcoholic steatohepatitis in mice

Abstract

Abstract: Objective To explore the effect and mechanism of dihydromyricetin（DHM） in improving nonalcoholic steatohepatitis （NASH） of mice induced by choline deficient L-amino acid restricted high-fat diet（CDAHFD）. Methods The NASH model was established by feeding C57BL/6J mice with CDAHFD for 4 weeks. Twenty-four male mice were randomly divided into three groups（CT,CDAHFD,and DHM）,the CT group was provided with the standard food,and other groups were fed with the CDAHFD diet. Mice in the DHM group were gavaged with 200 mg/kg·bw DHM daily. Mice in CT and CDAHFD groups were gavaged with normal saline. The food intake and body mass of mice were recorded. After 4 weeks of intervention,the biochemical indexes of serum and liver tissue were detected. To observe the histomorphologic changes of the liver,the HE,Oil red O,and Sirius red staining were performed. The relative mRNA expression levels of genes related to liver inflammation,lipid deposition,and fibrosis were determined by qRT-PCR. Results Compared with the CT group,the liver index of mice in the CDAHFD group was significantly increased（P<0.05）,and DHM intervention significantly reversed the serum alanine aminotransferase and aspartate aminotransferase levels induced by CDAHFD,as well as the NAFLD activity score. The content of liver triglyceride and total cholesterol content,the expression of fibrosis related genes in liver tissue（Co1α1,Col3α1,Timp1）,inflammatory and chemokine related genes（Tnf-α,Cxcl2,Cxcl10,Mcp1mRNA）,and the level of tumor necrosis factor-α,Interleukin-1 β protein in liver tissue increased（P<0.05）. Compared with CDAHFD group,DHM also increased the Pparα mRNA expression and glutathione as well as the superoxide dismutase content in liver（P<0.05）. The results of H&E staining,oil red O staining and Sirius red staining also showed that liver lipid deposition and collagen fiber deposition were significantly improved in DHM intervention group. Conclusion DHM can improve the liver injury,hepatic steatosis and fibrosis in CDAHFD induced NASH of mice. As for the mechanism,anti-inflammation and anti-oxidant maybe play a key role in the process.

Key words: Non-alcoholic steatohepatitis, Dihydromyricetin, Liver injury, Lipid deposition, Fibrosis

CLC Number:

R151.2

RAN Li, YAO Yu, HOU Pengfei, MI Mantian, ZHU Jundong. Effect and mechanism of dihydromyricetin improving choline-deficient and L-amino acid-restricted high-fat diet-induced non-alcoholic steatohepatitis in mice. [J]OCCUPATION AND HEALTH, 2024, 40(19): 2612-2618.

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