Effect of Qizhu prescription on a mouse model of non-alcoholic fatty liver disease incluced by high-fat， high-fructose， and high-cholesterol diet and its mechanism
Journal Title: Journal of Clinical Hepatology - Year 2024, Vol 40, Issue 11
Abstract
[Objective] To investigate the therapeutic effect and mechanism of action of Qizhu prescription in mice with non-alcoholic fatty liver disease （NAFLD）. [Methods] A total of 60 male C57BL/6J mice were randomly divided into normal group， model group， low-dose Qizhu prescription group （4.75 g/kg）， middle-dose Qizhu prescription group （9.50 g/kg）， high-dose Qizhu prescription group （19.00 g/kg）， Yishanfu group （228 mg/kg）， with 10 mice in each group. After 16 weeks of modeling with a high-fat high-cholesterol diet and 20% fructose water， each group was given the corresponding drug once a day for 8 weeks. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein （LDL） were measured； ELISA was used to measure the serum levels of free fatty acid （FFA）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， superoxide dismutase （SOD）， and malondialdehyde （MDA）； HE staining and oil red O staining were used to the pathological changes of liver tissue； Western blot was used to measure the protein expression levels of LC3BⅡ/Ⅰ， p62/SQSTM1， Beclin-1， and Drp1， and real-time PCR was used to measure the mRNA expression levels of Drp1， Beclin-1， and p62/SQSTM1. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. [Results] Compared with the normal group， the model groups had significant increases in the serum levels of TG， TC， ALT， AST， LDL， FFA， TNF-α， IL-1β， and MDA and a significant reduction in the serum level of SOD （P<0.05）. HE staining showed that the mice in the model group had hepatocyte steatosis and a large number of fat vacuoles in liver tissue， and oil red O staining showed that the mice in the model group had a large number of red lipid droplets of varying sizes in hepatocytes， with a significant increase in the percentage of oil red O staining area compared with the normal group （P<0.05）. Real-time PCR showed that compared with the normal group， the model group had significant increases in the mRNA expression levels of Drp1 and Beclin-1 and a significant reduction in the mRNA expression level of p62/SQSTM1 in liver tissue （all P<0.05）， and Western blot showed that compared with the normal group， the model group had significant increases in the protein expression levels of Drp1， Beclin-1， and LC3BⅡ/Ⅰ and a significant reduction in the protein expression level of p62/SQSTM1 in liver tissue （all P<0.05）. Compared with the model group， some Qizhu prescription groups and the Yishanfu group had significant reductions in the serum levels of TG， TC， ALT， AST， LDL， FFA， TNF-α， IL-1β， and MDA and a significant increase in the serum level of SOD （all P<0.05）. Compared with the model group， each administration group had a significant improvement in steatosis of liver tissue， a significant reduction in the percentage of oil red O staining area， significant reductions in the mRNA expression levels of Drp1 and Beclin-1， and a significant increase in the mRNA expression level of p62/SQSTM1 （all P<0.05）； there were significant reductions in the protein expression levels of Drp1， Beclin-1， and LC3BⅡ/Ⅰ， while some administration groups had a significant increase in the protein expression level of p62/SQSTM1 （all P<0.05）， with a significantly better effect in the middle- and high-dose Qizhu prescription groups （all P<0.01）. [Conclusion] Qizhu prescription improves lipid metabolism and inflammation in mice with NAFLD possibly by regulating hepatocyte mitophagy.
Authors and Affiliations
Jiahao CHEN, Zhenhua ZHOU
Keywords
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- EP ID EP753507
- DOI 10.12449/JCH241113
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