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Thirty male BALB\/c mice were divided randomly into five groups. The mice were orally treated with either disassembled prescriptions of YFJP or saline solution continuously for 14\u2009days. The mice were weighed every 2\u2009days during treatment and the appearance of tumors was observed by photographing. The tumor inhibition rate and the spleen and thymus indexes were calculated. Hematoxylin and eosin and immunohistochemical staining were performed to observe the histological changes and tumor\u2010infiltrating lymphocytes. Cell apoptosis was determined by terminal deoxynucleotidyl transferase\u2010mediated dUTP nick\u2010end labeling staining. The proportion of CD8<jats:sup>+<\/jats:sup> T cells and the expression of programmed cell death protein 1 (PD\u20101), T cell immunoglobulin domain and mucin domain\u20103 (Tim\u20103), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were analyzed using flow cytometry. The production of serum cytokines was detected using the Milliplex\u00ae MAP mouse high sensitivity T cell panel kit. The active components of the key drugs and HCC\u2010related target proteins were obtained from the corresponding databases. The putative targets for HCC treatment were screened by target mapping, and potential active components were screened by constructing a component\u2010target network. The interactive targets of putative targets were obtained from the STRING database to construct the protein\u2013protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed based on potential targets. The gene\u2013gene inner and component\u2010target\u2010pathway networks were constructed and analyzed to screen the key targets. Western blotting was used to evaluate the protein expression of the key targets in the tumor\u2010bearing mouse model. The binding activity of the key targets and compounds was verified by molecular docking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the three disassembled prescriptions of YFJP, the Fuzheng prescription (FZP) showed significant antitumor effects and inhibited weight loss during the treatment of H22 tumor\u2010bearing mice. FZP increased the immune organ index and the levels of CD8<jats:sup>+<\/jats:sup> and CD3<jats:sup>+<\/jats:sup> T cells in the spleen and peripheral blood of H22 tumor\u2010bearing mice. FZP also reduced the expression of PD\u20101, TIGIT, and TIM3 in CD8<jats:sup>+<\/jats:sup> T cells and the production of IL\u201010, IL\u20104, IL\u20106, and IL\u20101\u03b2. Network pharmacology and experimental validation showed that the key targets of FZP in the treatment of HCC were PIK3CA, TP53, MAPK1, MAPK3, and EGFR. The therapeutic effect on HCC was evaluated based on HCC\u2010related signaling pathways, including the PIK3\u2010Akt signaling pathway, PD\u2010L1 expression, and PD\u20101 checkpoint pathway in cancer. GO enrichment analysis indicated that FZP positively regulated the molecular functions of transferases and kinases on the cell surface through membrane raft, membrane microarea, and other cell components to inhibit cell death and programmed cell death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>FZP was found to be the key disassembled prescription of YFJP that exerted antitumor and immunoregulatory effects against HCC. FZP alleviated T cell exhaustion and improved the immunosuppressive microenvironment via HCC\u2010related targets, pathways, and biological processes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5064","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T09:42:09Z","timestamp":1661938929000},"page":"3237-3259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mechanisms and network pharmacological analysis of Yangyin Fuzheng Jiedu prescription in the treatment of hepatocellular carcinoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Yuqing","family":"Xie","sequence":"first","affiliation":[{"name":"Center of Integrative Medicine, Beijing Ditan Hospital Capital Medical University  Beijing P.R. 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