中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 3
Mar.  2024
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(3): 502-508

Role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis

DOI: 10.12449/JCH240311

  • School of Basic Medical Sciences，Shanxi University of Chinese Medicine，Jinzhong，Shanxi 030619，China

Research funding:

Shanxi Provincial Key Country Science and Technology Cooperation Project Shanxi Provincial Science and Technology Department (202104041101013);

Science and Technology Innovation Team Project of Shanxi University of Traditional Chinese Medicine (2022TD2003);

Key Team of Science and Technology Innovation Talents of Shanxi Province for Prevention and Treatment of Rheumatological and Immunological diseases by Integrated Chinese and Western Medicine (202204051002033);

Discipline Construction Project of Shanxi University of Traditional Chinese Medicine (2023XKJS-03);

Natural Science Foundation Project of Shanxi Province (202203021222272)

More Information
  • Corresponding author: LIU Yang， liuyang1980@sxtcm.edu.cn （ORCID： 0000-0002-6627-5002）
  • Received Date: 2023-06-09
  • Accepted Date: 2023-08-15
  • Published Date: 2024-03-20
    Abstract
  •   Objective  To investigate the role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis.  Methods  A total of 18 specific pathogen-free female C57BL/6 mice were selected and divided into normal group， model group， and treatment group using a random number table， with 6 mice in each group. The mice in the model group and the treatment group were injected with concanavalin A （Con A） via the caudal vein to establish a mouse model of autoimmune hepatitis， and those in the normal group were injected with normal saline. The mice in the treatment group were given prophylactic treatment with Yinchenhao Decoction （4.68 g crude drug/kg） by gavage at 14 days before modeling， and Con A was injected after the last gavage. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interferon gamma （IFN-γ）， tumor necrosis factor-α （TNF-α）， iron ion， glutathione （GSH）， reactive oxygen species （ROS）， adenosine triphosphate （ATP）， and malondialdehyde （MDA） were measured； liver index and spleen index were calculated； the expression levels of GPX4 and SLC7A11 were measured； liver histopathological changes were compared between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the least significant difference t-test was used for further comparison between two groups.  Results  Compared with the normal group， the model group had significant increases in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant reductions in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. Compared with the model group， the treatment group had significant reductions in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant increases in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. HE staining showed that compared with the normal group， the model group showed massive hepatocyte degeneration and necrosis and inflammatory cell aggregation at the portal area， and compared with the model group， the treatment group had alleviation of liver necrosis and inflammatory infiltration.  Conclusion  Liver injury induced by Con A may be associated with ferroptosis. Yinchenhao Decoction can increase the protein expression levels of SLC7A11 and GPX4 protein and thus inhibit ferroptosis of hepatocytes induced by Con A.

     

    • FullText(HTML)
  • loading
    • References(32)
  • [1]
    TL J, MIQUEL R, ZACHOU K, et al. Features and outcome of AIH patients without elevation of IgG[J]. JHEP Rep, 2020, 2( 3): 100094. DOI: 10.1016/j.jhepr.2020.100094.
    [2]
    MIELI-VERGANI G, VERGANI D, CZAJA AJ, et al. Autoimmune hepatitis[J]. Nat Rev Dis Primers, 2018, 4: 18017. DOI: 10.1038/nrdp.2018.17.
    [3]
    PAPE S, SNIJDERS RJALM, GEVERS TJG, et al. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group[J]. J Hepatol, 2022, 76( 4): 841- 849. DOI: 10.1016/j.jhep.2021.12.041.
    [4]
    European Association for the Study of the Liver. EASL clinical practice guidelines: Autoimmune hepatitis[J]. J Hepatol, 2015, 63( 4): 971- 1004. DOI: 10.1016/j.jhep.2015.06.030.
    [5]
    LV T, LI M, ZENG N, et al. Systematic review and meta-analysis on the incidence and prevalence of autoimmune hepatitis in Asian, European, and American population[J]. J Gastroenterol Hepatol, 2019, 34( 10): 1676- 1684. DOI: 10.1111/jgh.14746.
    [6]
    TRIVEDI PJ, HIRSCHFIELD GM. Recent advances in clinical practice: Epidemiology of autoimmune liver diseases[J]. Gut, 2021, 70( 10): 1989- 2003. DOI: 10.1136/gutjnl-2020-322362.
    [7]
    ZHANG KH, LI JC, SHI Z, et al. Ginsenosides regulates innate immunity to affect immune microenvironment of AIH through hippo-YAP/TAZ signaling pathway[J]. Front Immunol, 2022, 13: 851560. DOI: 10.3389/fimmu.2022.851560.
    [8]
    CHEN SQ. Treating of autoimmune hepatitis with removing heat and dampness of Prof. ZHOU zhongying[J]. J Pract Tradit Chin Intern Med, 2013, 27( 1): 16, 18. DOI: 10.3969/j.issn.1671-7813.2013.01(s).08.

    陈四清. 周仲瑛教授清热化湿治疗免疫性肝炎[J]. 实用中医内科杂志, 2013, 27( 1): 16, 18. DOI: 10.3969/j.issn.1671-7813.2013.01(s).08.
    [9]
    LI S, SHI MJ, XIAO HM, et al. Data mining for diagnosis and treatment law of autoimmune hepatitis based on Chinese medical records[J]. J Tradit Chin Med, 2017, 58( 14): 1237- 1240. DOI: 10.13288/j.11-2166/r.2017.14.017.

    黎胜, 施梅姐, 萧焕明, 等. 自身免疫性肝炎中医医案诊治规律数据挖掘[J]. 中医杂志, 2017, 58( 14): 1237- 1240. DOI: 10.13288/j.11-2166/r.2017.14.017.
    [10]
    ZHU LJ, CHEN DZ, ZHU Y, et al. GPX4-regulated ferroptosis mediates S100-induced experimental autoimmune hepatitis associated with the Nrf2/HO-1 signaling pathway[J]. Oxid Med Cell Longev, 2021, 2021: 6551069. DOI: 10.1155/2021/6551069.
    [11]
    CHEN X, KANG R, KROEMER G, et al. Ferroptosis in infection, inflammation, and immunity[J]. J Exp Med, 2021, 218( 6): e20210518. DOI: 10.1084/jem.20210518.
    [12]
    LEE H, ZANDKARIMI F, ZHANG YL, et al. Energy-stress-mediated AMPK activation inhibits ferroptosis[J]. Nat Cell Biol, 2020, 22( 2): 225- 234. DOI: 10.1038/s41556-020-0461-8.
    [13]
    WANG KC, WU WR, JIANG XW, et al. Multi-omics analysis reveals the protection of gasdermin D in concanavalin A-induced autoimmune hepatitis[J]. Microbiol Spectr, 2022, 10( 5): e0171722. DOI: 10.1128/spectrum.01717-22.
    [14]
    LI J, ZUO ZY. Formulas of Chinese Medicine[M]. Fifth Edition. Beijing: China Press of Traditional Chinese Medicine, 2021: 237- 238.

    李冀, 左铮云. 方剂学[M]. 第五版. 北京: 中国中医药出版社, 2021: 237- 238.
    [15]
    SHEN H, HUANG YY, CHEN T, et al. Optimization of the water extraction for Yinchenhao Decoction by orthogonal experimental design[J]. China Pharm, 2020, 29( 11): 14- 17. DOI: 10.3969/j.issn.1006-4931.2020.11.004.

    沈晗, 黄玉宇, 陈汀, 等. 正交试验设计优选茵陈蒿汤水煎煮工艺[J]. 中国药业, 2020, 29( 11): 14- 17. DOI: 10.3969/j.issn.1006-4931.2020.11.004.
    [16]
    LU Y, SUN FF, ZENG Z, et al. Research advances on autoimmune hepatitis[J/CD]. Chin J Liver Dis(Electronic Version), 2022, 14( 4): 1- 9. DOI: 10.3969/j.issn.1674-7380.2022.04.001.

    路遥, 孙芳芳, 曾湛, 等. 自身免疫性肝炎研究进展[J/CD]. 中国肝脏病杂志(电子版), 2022, 14( 4): 1- 9. DOI: 10.3969/j.issn.1674-7380.2022.04.001.
    [17]
    MACK CL, ADAMS D, ASSIS DN, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American association for the study of liver diseases[J]. Hepatology, 2020, 72( 2): 671- 722. DOI: 10.1002/hep.31065.
    [18]
    LOHSE AW, SEBODE M, BHATHAL PS, et al. Consensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group: Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology: Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology[J]. Liver Int, 2022, 42( 5): 1058- 1069. DOI: 10.1111/liv.15217.
    [19]
    Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the diagnosis and management of autoimmune hepatitis(2021)[J]. J Clin Hepatol, 2022, 38( 1): 42- 49.

    中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021)[J]. 临床肝胆病杂志, 2022, 38( 1): 42- 49.
    [20]
    WANG LY, LIU YC, DU TT, et al. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc[J]. Cell Death Differ, 2020, 27( 2): 662- 675. DOI: 10.1038/s41418-019-0380-z.
    [21]
    GUO YF, SUN FX, LI XL, et al. Clinical application of Yinchenhao Decoction in hepatobiliary disease[J]. J Liaoning Univ Tradit Chin Med, 2020, 22( 3): 57- 60. DOI: 10.13194/j.issn.1673-842x.2020.03.016.

    郭雨菲, 孙凤霞, 李晓玲, 等. 茵陈蒿汤在肝胆疾病中临床应用[J]. 辽宁中医药大学学报, 2020, 22( 3): 57- 60. DOI: 10.13194/j.issn.1673-842x.2020.03.016.
    [22]
    ZHANG JY, LIU XK, WU JR, et al. A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao Decoction on hepatitis C based on network pharmacology[J]. BMC Complement Med Ther, 2020, 20( 1): 50. DOI: 10.1186/s12906-020-2823-y.
    [23]
    LI DH, WU HW, ZHANG SJ, et al. New progress in pharmacological action of Yinchenhao Decoction[J]. Gansu Sci Technol, 2021, 37( 11): 151- 154. DOI: 10.3969/j.issn.1000-0952.2021.11.045.

    李东辉, 吴红伟, 张淑娟, 等. 茵陈蒿汤药理作用研究新进展[J]. 甘肃科技, 2021, 37( 11): 151- 154. DOI: 10.3969/j.issn.1000-0952.2021.11.045.
    [24]
    YUAN HS, PRATTE J, GIARDINA C. Ferroptosis and its potential as a therapeutic target[J]. Biochem Pharmacol, 2021, 186: 114486. DOI: 10.1016/j.bcp.2021.114486.
    [25]
    XIONG H, ZHANG AH, GUO YJ, et al. A clinical and animal experiment integrated platform for small-molecule screening reveals potential targets of bioactive compounds from a herbal prescription based on the therapeutic efficacy of Yinchenhao Tang for jaundice syndrome[J]. Engineering, 2021, 7( 9): 213- 238.
    [26]
    YAO YQ, CAO Q, WANG X, et al. Identification of constituents in vitro and blood-absorbed ingredients of protective effect on acute liver injury from Yin Chen Hao Decoction based on UPLC-QTOF/MS[J]. Acta Pharm Sin, 2023, 58( 5): 1173- 1180. DOI: 10.16438/j.0513-4870.2022-1139.

    姚一青, 曹奇, 王璇, 等. 基于UPLC-QTOF/MS的茵陈蒿汤体外成分鉴定和急性肝损伤防护作用入血成分研究[J]. 药学学报, 2023, 58( 5): 1173- 1180. DOI: 10.16438/j.0513-4870.2022-1139.
    [27]
    CHEN YT, LUO GM, ZHOU L, et al. Discussion on the mechanism of Yinchenhao Decoction in treating intrahepatic cholestasis of pregnancy based on network pharmacology-molecular docking[J]. Mod Tradit Chin Med Mater Med World Sci Technol, 2021, 23( 5): 1588- 1597. DOI: 10.11842/wst.20210105007.

    陈云婷, 罗光明, 周丽, 等. 基于网络药理学-分子对接探讨茵陈蒿汤治疗妊娠期肝内胆汁淤积症的作用机制[J]. 世界科学技术-中医药现代化, 2021, 23( 5): 1588- 1597. DOI: 10.11842/wst.20210105007.
    [28]
    SHI XH, MANG J, XU ZX. Research progress in cell death modes of cerebral ischemia-reperfusion injury[J]. J Jilin Univ:Med Edit, 2022, 48( 6): 1635- 1643. DOI: 10.13481/j.1671-587X.20220633.

    石晓花, 莽靖, 徐忠信. 脑缺血再灌注损伤细胞死亡模式的研究进展[J]. 吉林大学学报(医学版), 2022, 48( 6): 1635- 1643. DOI: 10.13481/j.1671-587X.20220633.
    [29]
    YUAN Y, ZHAI YY, CHEN JJ, et al. Kaempferol ameliorates oxygen-glucose deprivation/reoxygenation-induced neuronal ferroptosis by activating Nrf2/SLC7A11/GPX4 axis[J]. Biomolecules, 2021, 11( 7): 923. DOI: 10.3390/biom11070923.
    [30]
    YANG WC, WANG YX, ZHANG CG, et al. Maresin1 protect against ferroptosis-induced liver injury through ROS inhibition and Nrf2/HO-1/GPX4 activation[J]. Front Pharmacol, 2022, 13: 865689. DOI: 10.3389/fphar.2022.865689.
    [31]
    LEI XG, ZHU JH, CHENG WH, et al. Paradoxical roles of antioxidant enzymes: Basic mechanisms and health implications[J]. Physiol Rev, 2016, 96( 1): 307- 364. DOI: 10.1152/physrev.00010.2014.
    [32]
    TANG HM, TANG HL. Cell recovery by reversal of ferroptosis[J]. Biol Open, 2019, 8( 6): bio043182. DOI: 10.1242/bio.043182.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(2)  / Tables(3)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (362) PDF downloads(43) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return