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

Jiahao CHEN; Zhenhua ZHOU

doi:10.12449/JCH241113

Volume 40 Issue 11

Nov. 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(11): 2205-2212

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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

DOI: 10.12449/JCH241113

Jiahao CHEN^1a,
Zhenhua ZHOU^{1b, 2
,
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1a.
Cellular Immunity Laboratory，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China
1b.
Department of Hepatology，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China
2.
Department of Hepatology，Anhui Hospital，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Hefei 230011，China

Research funding:

Shanghai 2021 “Science and Technology Innovation Action Plan” Biomedical Science and Technology Support Special Project (21S1900400);

Natural Science Foundation of Anhui Province (2308085MH293);

Key Scientific Research Project of Anhui Province (2023AH040098);

Health as a key project of scientific research in anhui province (AHWJ2023A10035);

The state administration of traditional Chinese medicine high level key discipline construction project of traditional Chinese medicine （TCM liver epidemiology） (zyyzdxk-2023060)

More Information

Corresponding author: ZHOU Zhenhua， jinghua1220@163.com （ORCID： 0000-0002-5639-3857）
Received Date: 2024-05-23
Accepted Date: 2024-07-11
Published Date: 2024-11-25

Abstract

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.
- Non-alcoholic Fatty Liver Disease,
- Qi Zhu Formula,
- Mitophagy,
- Lipid Metabolism,
- Inflammation

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References

[1]	QUEK J, CHAN KE, WONG ZY, et al. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: A systematic review and meta-analysis[J]. Lancet Gastroenterol Hepatol, 2023, 8( 1): 20- 30. DOI: 10.1016/S2468-1253(22)00317-X.
[2]	WONG VWS, EKSTEDT M, WONG GLH, et al. Changing epidemiology, global trends and implications for outcomes of NAFLD[J]. J Hepatol, 2023, 79( 3): 842- 852. DOI: 10.1016/j.jhep.2023.04.036.
[3]	CHEN JH, ZHOU ZH. Research progress of abnormal lipid metabolism and mitochondrial dysfunction in the pathogenesis and disease process of NAFLD[J]. Chin Hepatol, 2023, 28( 11): 1372- 1375. DOI: 10.3969/j.issn.1008-1704.2023.11.027. 陈佳豪, 周振华. 肝细胞脂质代谢异常与线粒体功能障碍在NAFLD发病和疾病进程中的研究进展[J]. 肝脏, 2023, 28( 11): 1372- 1375. DOI: 10.3969/j.issn.1008-1704.2023.11.027.
[4]	REN QN, SUN QM, FU JF. Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease[J]. Autophagy, 2024, 20( 2): 221- 241. DOI: 10.1080/15548627.2023.2254191.
[5]	XIN YJ, CHEN YY, YANG HL, et al. Effect of Xuanfuhua Decoction on a mouse model of nonalcoholic steatohepatitis induced by high-fat, high-fructose, and high-cholesterol diet[J]. J Clin Hepatol, 2023, 39( 6): 1340- 1350. DOI: 10.3969/j.issn.1001-5256.2023.06.014. 辛一敬, 陈逸云, 杨海琳, 等. 旋覆花汤对高脂高果糖高胆固醇饮食诱导非酒精性脂肪性肝炎小鼠模型的影响[J]. 临床肝胆病杂志, 2023, 39( 6): 1340- 1350. DOI: 10.3969/j.issn.1001-5256.2023.06.014.
[6]	ZHANG QY, ZHOU ZH. Mechanism of non-alcoholic steatohepatitis improved by Qizhu prescription based on AMPK signaling pathway[J]. Chin J Exp Tradit Med Formulae, 2024, 30( 8): 49- 56. DOI: 10.13422/j.cnki.syfjx.20232237. 张秋怡, 周振华. 基于AMPK信号通路探讨芪术方改善非酒精性脂肪性肝炎的机制[J]. 中国实验方剂学杂志, 2024, 30( 8): 49- 56. DOI: 10.13422/j.cnki.syfjx.20232237.
[7]	FAKHOURY-SAYEGH N, TRAK-SMAYRA V, SAYEGH R, et al. Fructose threshold for inducing organ damage in a rat model of nonalcoholic fatty liver disease[J]. Nutr Res, 2019, 62: 101- 112. DOI: 10.1016/j.nutres.2018.11.003.
[8]	CHEN Z, TIAN RF, SHE ZG, et al. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease[J]. Free Radic Biol Med, 2020, 152: 116- 141. DOI: 10.1016/j.freeradbiomed.2020.02.025.
[9]	SCHUSTER S, CABRERA D, ARRESE M, et al. Triggering and resolution of inflammation in NASH[J]. Nat Rev Gastroenterol Hepatol, 2018, 15( 6): 349- 364. DOI: 10.1038/s41575-018-0009-6.
[10]	ZHANG DW, ZHAO HY, LI QS, et al. Effect of AstragalosideIV and ginsenoside Rg1 on autophagy of myocardial tissue injury induced by ischemia-reperfusion injury in hyperlipidemic mice[J]. Chin Arch Tradit Chin Med, 2020, 38( 3): 60- 64. DOI: 10.13193/j.issn.1673-7717.2020.03.016. 张东伟, 赵宏月, 李全生, 等. 黄芪甲苷及人参皂苷Rg1对高脂大鼠心肌缺血再灌注损伤后心肌线粒体自噬的影响[J]. 中华中医药学刊, 2020, 38( 3): 60- 64. DOI: 10.13193/j.issn.1673-7717.2020.03.016.
[11]	SU J, GAO CT, XIE L, et al. Astragaloside II ameliorated podocyte injury and mitochondrial dysfunction in streptozotocin-induced diabetic rats[J]. Front Pharmacol, 2021, 12: 638422. DOI: 10.3389/fphar.2021.638422.
[12]	LI SD, CHEN XJ, LIU JK, et al. Signaling pathways involved in the active components of Polygonum cuspidatum in treatment of nonalcoholic fatty liver disease and their interaction[J]. J Clin Hepatol, 2022, 38( 4): 902- 907. DOI: 10.3969/j.issn.1001-5256.2022.04.033. 李淑娣, 陈欣菊, 刘江凯, 等. 虎杖活性成分治疗非酒精性脂肪性肝病的相关信号通路及相互作用[J]. 临床肝胆病杂志, 2022, 38( 4): 902- 907. DOI: 10.3969/j.issn.1001-5256.2022.04.033.
[13]	WANG Y, YANG ZY, LI SQ, et al. Regulatory mechanism of Polygonidine on endoplasmic reticulum stress in non⁃alcoholic fatty hepatocytes[J]. Anatomy Research, 2023, 45( 1): 57- 62. DOI: 10.20021/j.cnki.1671-0770.2023.01.10. 王懿, 杨志勇, 李书芹, 等. 虎杖苷对非酒精性脂肪性肝细胞内质网应激的调控机制[J]. 解剖学研究, 2023, 45( 1): 57- 62. DOI: 10.20021/j.cnki.1671-0770.2023.01.10.
[14]	ZHANG PF, CHENG XY, SUN HM, et al. Atractyloside protect mice against liver steatosis by activation of autophagy via ANT-AMPK-mTORC1 signaling pathway[J]. Front Pharmacol, 2021, 12: 736655. DOI: 10.3389/fphar.2021.736655.
[15]	UENO T, KOMATSU M. Autophagy in the liver: Functions in health and disease[J]. Nat Rev Gastroenterol Hepatol, 2017, 14( 3): 170- 184. DOI: 10.1038/nrgastro.2016.185.
[16]	MA XW, MCKEEN T, ZHANG JH, et al. Role and mechanisms of mitophagy in liver diseases[J]. Cells, 2020, 9( 4): 837. DOI: 10.3390/cells9040837.
[17]	LU YY, LI ZJ, ZHANG SQ, et al. Cellular mitophagy: Mechanism, roles in diseases and small molecule pharmacological regulation[J]. Theranostics, 2023, 13( 2): 736- 766. DOI: 10.7150/thno.79876.
[18]	LI L, JIA QL, WANG XX, et al. Chaihu Shugan San promotes gastric motility in rats with functional dyspepsia by regulating Drp-1-mediated ICC mitophagy[J]. Pharm Biol, 2023, 61( 1): 249- 258. DOI: 10.1080/13880209.2023.2166966.
[19]	LIU T, YU JN, LIU Y, et al. Effects of serum-free starvation on proliferative capacity of muscle satellite cells and expression of autophagy-related proteins LC3 and Beclin1[J]. Chin J Tissue Eng Res, 2019, 23( 11): 1657- 1661. DOI: 10.3969/j.issn.2095-4344.1062. 刘通, 于佳妮, 刘悦, 等. 去血清饥饿条件下肌卫星细胞增殖及自噬蛋白LC3、Beclin1的表达[J]. 中国组织工程研究, 2019, 23( 11): 1657- 1661. DOI: 10.3969/j.issn.2095-4344.1062.
[20]	SUI XY, XU P, DUAN CZ, et al. Advances in molecular function of p62 protein and its role in diseases[J]. Chin J Biotechnol, 2023, 39( 4): 1374- 1389. DOI: 10.13345/j.cjb.220681. 隋馨莹, 徐平, 段昌柱, 等. p62蛋白的分子功能及其在疾病中的研究进展[J]. 生物工程学报, 2023, 39( 4): 1374- 1389. DOI: 10.13345/j.cjb.220681.
[21]	YAO RQ, REN C, XIA ZF, et al. Organelle-specific autophagy in inflammatory diseases: A potential therapeutic target underlying the quality control of multiple organelles[J]. Autophagy, 2021, 17( 2): 385- 401. DOI: 10.1080/15548627.2020.1725377.

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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

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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

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