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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 7
Jul.  2022
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Article Contents

Mechanism of Lingmao Formula in treatment of chronic hepatitis B based on network pharmacology and animal experiment

DOI: 10.3969/j.issn.1001-5256.2022.07.010
Research funding:

National Natural Science Foundation of China (81774256);

National Natural Science Foundation of China (81874436)

More Information
  • Corresponding author: GAO Yueqiu, gaoyueqiu@hotmail.com (ORCID: 0000-0001-7276-9810)
  • Received Date: 2021-10-29
  • Accepted Date: 2021-12-17
  • Published Date: 2022-07-20
  •   Objective  To investigate the association between Lingmao Formula and type Ⅰ interferon in the treatment of chronic hepatitis B.  Methods  TCMSP database was used to obtain the main active components of Lingmao Formula; Genecards database was used to obtain the targets of Lingmao Formula and chronic hepatitis B; Bioinformatics was used to obtain the intersection of drug targets and disease targets, plot Venn diagram, and perform GO enrichment analysis, and DAVID 6.8 was used for KEGG enrichment analysis; CytoScape 3.8.0 was used to obtain immune response-related pathways. A total of 30 specific pathogen-free male C57BL/6N mice were randomly divided into normal group, model group, and Lingmao Formula group, with 10 mice in each group. All mice except those in the normal group were used to establish a model of HBV replication in vivo by hydrodynamic transfection; the mice in Lingmao Formula group were given Lingmao Formula by gavage, twice a day for 3 days, and those in the model group and the normal group were given an equal volume of normal saline by gavage. Serum samples were collected after the experiment ended and ELISA was used to measure the changes in the levels of HBsAg, HBeAg, and type Ⅰ interferon. The independent samples t-test was used for comparison of continuous data between two groups, and one-way ANOVA combined with the least significant difference t-test was used for multiple comparisons between groups.  Results  Network pharmacology obtained 22 active components and 6059 action targets of Lingmao Formula, 481 targets associated with chronic hepatitis, and 387 drug-disease intersecting targets and proposed the hypothesis that Lingmao Formula participated in hepatitis B-related immune response by regulating type Ⅰ interferon. Animal experiments confirmed that compared with the model group, the Lingmao Formula group had significant reductions in HBsAg (t=2.227, P=0.043) and HBeAg (t=2.488, P=0.026), with significantly greater reductions in HBsAg (t=-4.603, P < 0.001) and HBeAg (t=-2.224, P=0.043); compared with the normal group, the model group had no significant changes in the levels of IFNα and IFNβ (P > 0.05), and the Lingmao Formula group had significant increases in the levels of IFNα and IFNβ (P < 0.001); compared with the model group, the Lingmao Formula group also had significant increases in the levels of IFNα and IFNβ (P < 0.001).  Conclusion  Lingmao Formula exerts an anti-HBV effect by regulating the secretion of type Ⅰ interferon.

     

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  • [1]
    Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.

    中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648- 2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
    [2]
    CHEN BW, ZHU XJ, ZHANG X, et al. Influence of virologic response on disease progression in patients with compensated hepatitis B cirrhosis[J]. J Clin Hepatol, 2021, 37(8): 1811-1816. DOI: 10.3969/j.issn.1001-5256.2021.08.014.

    陈博武, 朱晓骏, 张鑫, 等. 病毒学应答状态对代偿期乙型肝炎肝硬化患者疾病进展的影响[J]. 临床肝胆病杂志, 2021, 37(8): 1811-1816. DOI: 10.3969/j.issn.1001-5256.2021.08.014.
    [3]
    WU L, ZHANG ZP, CAI WT, et al. Research progress on anti-hepatitis B virus activity and mechanisms of traditional Chinese medicine[J]. Chin Tradit Herb Drug, 2020, 51(24): 6367-6376. DOI: 10.7501/j.issn.0253-2670.2020.24.028.

    伍磊, 张志鹏, 蔡文涛, 等. 中药抗乙肝病毒活性及作用机制的研究进展[J]. 中草药, 2020, 51(24): 6367-6376. DOI: 10.7501/j.issn.0253-2670.2020.24.028.
    [4]
    ZHU XJ, ZHANG X, ZHOU ZH, et al. The lingmao formula suppresses the replication of hepatitis B virus by enhancing innate immune response[J]. Chin J Integr Tradit West Med Liver Dis, 2018, 28(1): 33-36. DOI: 10.3969/j.issn.1005-0264.2018.01.012.

    朱晓骏, 张鑫, 周振华, 等. 灵猫方通过增强天然免疫功能抑制乙型肝炎病毒复制的研究[J]. 中西医结合肝病杂志, 2018, 28(1): 33-36. DOI: 10.3969/j.issn.1005-0264.2018.01.012.
    [5]
    ZENG ZJ, LI M, SUN XH, et al. Effects of Lingmao forumla and its actions against hepatic fibrosis[J/CD]. Chin J Clinicians (Electronic Edition), 2012, 6(15): 4258-4262. DOI: 10.3877/cma.j.issn.1674-0785.2012.15.023.

    曾震军, 李曼, 孙学华, 等. 中药灵猫方的抗肝纤维化作用及其机制[J/CD]. 中华临床医师杂志(电子版), 2012, 6(15): 4258-4262. DOI: 10.3877/cma.j.issn.1674-0785.2012.15.023.
    [6]
    ZHANG X, ZHANG XW, DING J, et al. Effects of Lingmao recipe and its single herb alcohol extract on the expression of hepatitis B surface antigen and e antigen in HepG2.2.15 cells[J]. Hebei J TCM, 2017, 39(5): 729-734. DOI: 10.3969/j.issn.1002-2619.2017.05.022.

    张鑫, 张晞文, 丁俊, 等. 灵猫方及其单味药醇提物对HepG2.2.15细胞乙型肝炎表面抗原和乙型肝炎e抗原表达的影响[J]. 河北中医, 2017, 39(5): 729-734. DOI: 10.3969/j.issn.1002-2619.2017.05.022.
    [7]
    JIANG Y, GAO YQ, LI M, et al. Therapeutic effect of "Lingmao Decoction" combined with telbivudine in treating patients with chronic hepatitis B and the influence on the function of NK cells[J]. Acta Univ Tradit Med Sin Pharmacol Shanghai, 2017, 31(2): 16-21. DOI: 10.16306/j.1008-861x.2017.02.005.

    江云, 高月求, 李曼, 等. 灵猫方联合替比夫定治疗慢性乙型肝炎患者的疗效及对NK细胞功能的影响[J]. 上海中医药大学学报, 2017, 31(2): 16-21. DOI: 10.16306/j.1008-861x.2017.02.005.
    [8]
    JIANG Y, GAO YQ, LI GY. Experimental study of Lingmao Formula on protecting liver and reducing enzyme in acute liver injury model[J]. Chin J Tradit Med Sci Technol, 2012, 19(5): 406-407, 384. DOI: 10.3969/j.issn.1005-7072.2012.05.014.

    江云, 高月求, 李桂勇. 灵猫方对急性肝损伤模型保肝降酶作用的实验研究[J]. 中国中医药科技, 2012, 19(5): 406-407, 384. DOI: 10.3969/j.issn.1005-7072.2012.05.014.
    [9]
    RU J, LI P, WANG J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminform, 2014, 6: 13. DOI: 10.1186/1758-2946-6-13.
    [10]
    LAN SH, TANG QY, LI NN, et al. Mechanism of action of Xiaochaihu decoction in the treatment of hepatitis B based on network pharmacology[J]. J Clin Hepatol, 2021, 37(10): 2308- 2315. DOI: 10.3969/j.issn.1001-5256.2021.10.010.

    蓝绍航, 唐秋媛, 李娜娜, 等. 基于网络药理学研究小柴胡汤治疗乙型肝炎的作用机制[J]. 临床肝胆病杂志, 2021, 37(10) : 2308-2315. DOI: 10.3969/j.issn.1001-5256.2021.10.010.
    [11]
    YONEDA M, HYUN J, JAKUBSKI S, et al. Hepatitis B virus and DNA stimulation trigger a rapid innate immune response through NF-κB[J]. J Immunol, 2016, 197(2): 630-643. DOI: 10.4049/jimmunol.1502677.
    [12]
    Ll FL, HUA J, LU YP, et al. Research advances in innate immunity against hepatitis B virus[J]. J Clin Hepatol, 2016, 32(5): 992-996. DOI: 10.3969/j.issn.1001-5256.2016.05.044.

    李凤莉, 华娟, 卢银平, 等. HBV天然免疫的研究进展[J]. 临床肝胆病杂志, 2016, 32(5): 992-996. DOI: 10.3969/j.issn.1001-5256.2016.05.044.
    [13]
    BREZGIN S, KOSTYUSHEVA A, BAYUROVA E, et al. Immunity and viral infections: Modulating antiviral response via CRISPR-Cas systems[J]. Viruses, 2021, 13(7): 1373. DOI: 10.3390/v13071373.
    [14]
    IVASHKIV LB, DONLIN LT. Regulation of type Ⅰ interferon responses[J]. Nat Rev Immunol, 2014, 14(1): 36-49. DOI: 10.1038/nri3581.
    [15]
    XU F, SONG H, XIAO Q, et al. Type Ⅲ interferon-induced CBFβ inhibits HBV replication by hijacking HBx[J]. Cell Mol Immunol, 2019, 16(4): 357-366. DOI: 10.1038/s41423-018-0006-2.
    [16]
    LUCIFORA J, XIA Y, REISINGER F, et al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA[J]. Science, 2014, 343(6176): 1221-1228. DOI: 10.1126/science.1243462.
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