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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 8
Aug.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(8): 1848-1855

Mechanism of action of five classic prescriptions in treatment of hepatocellular carcinoma based on network pharmacology

DOI: 10.3969/j.issn.1001-5256.2021.08.020
  • 1.

    Liver Disease Center for Combined TCM and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China

  • 2.

    Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning 116044, China

  • 3.

    Department of TCM Dalian Hospital of Traditional Chinese Medicine, Dalian, Liaoning 116013, China

Research funding:

National Natural Science Foundation of China (81673728)

  • Received Date: 2021-01-10
  • Accepted Date: 2021-03-10
  • Published Date: 2021-08-20
    Abstract
  •   Objective  To investigate the mechanism of action of Xiaoyao powder combined with Sijunzi decoction, Artemisia capillaris Thunb. decoction, Longdan Xiegan decoction combined with Xiayuxue decoction, Wupi decoction combined with Sijunzi decoction, and Yiguan decoction in the treatment of hepatocellular carcinoma (HCC) based on network pharmacology and molecular docking.  Methods  Databases including TCMSP, TCMID, BATMAN-TCM, and TCM-MESH were used to screen out effective components and predict their targets, and databases including TTD, Drugbank, Disgenet, Liverome, OncoDB.HCC, and GEO were used to investigate HCC-related targets. The drug and disease targets were mapped to obtain the intersecting targets, and the visualization software Cytoscape 3.7.1 was used to construct the core component-intersecting target network and the protein-protein interaction (PPI) network. The core components and key genes were screened out and a survival analysis was performed in the GEPIA database. The active components and key genes screened out were imported into the DockThor online website for molecular docking. In addition, David database was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the intersecting targets.  Results  The analysis showed that 110, 19, 154, 121, and 51 active components, respectively, were obtained for the above five classic prescriptions, and the numbers of drug targets were 7426, 1435, 9544, 6619, and 2427, respectively. Finally 4001 HCC disease targets were screened out. There were 260, 169, 276, 242, and 192 intersecting targets, respectively, between the five prescriptions and the HCC disease targets, and the survival analysis on the GEPIA online website obtained the common hub genes of PIK3CA, SRC, MAPK1, MAPK3 (all P < 0.05) and AKT1 (P > 0.05). Quercetin was the common active component of the five prescriptions, and isobavachin and Kanzonol W were the common active components of Xiaoyao powder combined with Sijunzi decoction, Longdan Xiegan decoction combined with Xiayuxue decoction, and Wupi decoction combined with Sijunzi decoction; the results of molecular docking showed that the above three components had a strong ability of binding to PIK3CA and SRC. GO enrichment analysis showed that these targets were involved in various biological processes including drug response, protein phosphorylation, inflammatory response, and angiogenesis, and KEGG enrichment analysis showed that the common pathways involved were cancer pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, HIF-1 signaling pathway, hepatitis B pathway, and hepatitis C pathway.  Conclusion  Quercetin, isoflavone, and Kanzonol W have the potential mechanism of action involving multiple targets and pathways in the treatment of HCC.

     

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