{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T10:04:26Z","timestamp":1775642666093,"version":"3.50.1"},"reference-count":80,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":261,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["202040180"],"award-info":[{"award-number":["202040180"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2019-ZD-1072"],"award-info":[{"award-number":["2019-ZD-1072"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Matrine and glycyrrhizin are representative active ingredients of traditional Chinese medicine (TCM) used in clinical practice. Studies have demonstrated that matrine has antitumor pharmacological effects and that glycyrrhizin protects liver function. However, the potential bioactive compounds and mechanisms remain unknown, as well as whether they have synergistic effects in killing cancer cells and protecting liver cells. To investigate the synergistic effects and mechanism of matrine combined with glycyrrhizin in hepatocellular carcinoma (HCC) treatment, we used both network pharmacology and bioinformatics analyses. First, the chemical gene interaction information of matrine and glycyrrhizin was obtained from the PubChem database. The pathogenic genes of HCC were accessed from five public databases. The RNA sequencing data and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA). Next, the overlapping genes among the potential targets of matrine and glycyrrhizin and HCC\u2010related targets were determined using bioinformatics analysis. We constructed the drug\u2010target interaction network. Prognosis\u2010associated genes were acquired through the univariate Cox regression model and Lasso\u2010Cox regression model. The results were verified by the International Cancer Genome Consortium (ICGC) database. Finally, we predicted the immune function of the samples. The drug\u2010target interaction network consisted of 10 matrine and glycyrrhizin targets. We selected a Lasso\u2010Cox regression model consisting of 3 differentially expressed genes (DEGs) to predict the efficacy of the combination in HCC. Subsequently, we successfully predicted the overall survival of HCC patients using the constructed prognostic model and investigated the correlation of the immune response. Matrine and glycyrrhizin have synergistic effects on HCC. The model we obtained consisted of three drug\u2010target genes by Lasso\u2010Cox regression analysis. The model independently predicted the combined effect of matrine and glycyrrhizin in HCC treatment and OS, which will be helpful for guiding clinical treatment. The prognostic model was correlated with the immune cells and immune checkpoints of patients, which had an adjuvant effect on HCC immunotherapy. Matrine and glycyrrhizin can have therapeutic effects on HCC by promoting the production or enhancing the core gene activity in the drug network and improving the immune system function of patients.<\/jats:p>","DOI":"10.1155\/2022\/2663758","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T04:50:08Z","timestamp":1663649408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of the Mechanism of Matrine Combined with Glycyrrhizin for Hepatocellular Carcinoma Treatment through Network Pharmacology and Bioinformatics Analysis"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3814-8492","authenticated-orcid":false,"given":"Tao","family":"Han","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5289-3790","authenticated-orcid":false,"given":"Yiming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3516-9039","authenticated-orcid":false,"given":"Yutong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9839-5191","authenticated-orcid":false,"given":"Tingsong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8638-7378","authenticated-orcid":false,"given":"Yifan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1561-1835","authenticated-orcid":false,"given":"Qiuhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0183-144X","authenticated-orcid":false,"given":"Mingfang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000001474"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep24944"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00264-x"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27123798"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15351"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3242989"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-RW2016-056"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030635"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.118"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(04)03213-1"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2005.02.007"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1609"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2006.01.013"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2006.11.008"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/480S82a"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healthpol.2008.09.003"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/621423"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-8-58"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015939"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm862"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1126"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp1014"},{"key":"e_1_2_10_23_2","first-page":"2017","article-title":"Network target: a starting point for traditional Chinese medicine network pharmacology","volume":"36","author":"Li S.","year":"2011","journal-title":"China Journal of Chinese Materia Medica"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl363"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-5-S1-S10"},{"key":"e_1_2_10_26_2","first-page":"2920","article-title":"Network toxicology and its application to traditional Chinese medicine","volume":"36","author":"Fan X.","year":"2011","journal-title":"China Journal of Chinese Materia Medica"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms131013501"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/278405"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.113682"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107618"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.10.037"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.04.025"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2009.04.013"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa892"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.059"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0055-9"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti422"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113305"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568009616666151207105851"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-8741(91)90080-W"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.1089\/107555301753393823"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/761608"},{"key":"e_1_2_10_44_2","first-page":"819","article-title":"Yanhusuo extract inhibits metastasis of breast cancer cells by modulating mitogen-activated protein kinase signaling pathways","volume":"20","author":"Gao J.-L.","year":"2008","journal-title":"Oncology Reports"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/426521"},{"key":"e_1_2_10_46_2","first-page":"1077","article-title":"A traditional Chinese medicine formulation consisting of Rhizoma corydalis and Rhizoma Curcumae exerts synergistic anti-tumor activity","volume":"22","author":"Gao J.-L.","year":"2009","journal-title":"Oncology Reports"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2623"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06280.x"},{"key":"e_1_2_10_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-011-0068-9"},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X08006132"},{"key":"e_1_2_10_51_2","doi-asserted-by":"publisher","DOI":"10.2174\/1876142911002010012"},{"key":"e_1_2_10_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(15)60001-2"},{"key":"e_1_2_10_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00588"},{"key":"e_1_2_10_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-018-0634-4"},{"key":"e_1_2_10_55_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.3023"},{"key":"e_1_2_10_56_2","doi-asserted-by":"publisher","DOI":"10.1159\/000371736"},{"key":"e_1_2_10_57_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1034304"},{"key":"e_1_2_10_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2362"},{"key":"e_1_2_10_59_2","first-page":"128","article-title":"Protective effect of glycyrrhizin, glycyrrhetic acid and matrine on acute cholestasis induced by alpha-naphthyl isothiocyanate in rats","volume":"73","author":"Zhai D.","year":"2007","journal-title":"Planta Medica"},{"key":"e_1_2_10_60_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.30.1898"},{"key":"e_1_2_10_61_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093236"},{"key":"e_1_2_10_62_2","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000136"},{"key":"e_1_2_10_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.11.024"},{"key":"e_1_2_10_64_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2016.3805"},{"key":"e_1_2_10_65_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22353"},{"key":"e_1_2_10_66_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6331"},{"key":"e_1_2_10_67_2","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2019.4459"},{"key":"e_1_2_10_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113041"},{"key":"e_1_2_10_69_2","first-page":"1153","article-title":"The protective effect and mechanism of matrine combined with glycyrrhizin in carbon tetrachloride chronic liver injury","volume":"20","author":"Shun G.","year":"2017","journal-title":"Chinese Medicine"},{"key":"e_1_2_10_70_2","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B1400346"},{"key":"e_1_2_10_71_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.094797"},{"key":"e_1_2_10_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hepres.2005.08.002"},{"key":"e_1_2_10_73_2","first-page":"247","article-title":"Application of glutamate dehydrogenase detection in chronic hepatitis","volume":"4","author":"Yan C.","year":"2003","journal-title":"Shanghai Journal of Medical Testing"},{"key":"e_1_2_10_74_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-012-0183-0"},{"key":"e_1_2_10_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112898"},{"key":"e_1_2_10_76_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.903570"},{"key":"e_1_2_10_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108091"},{"key":"e_1_2_10_78_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00347"},{"key":"e_1_2_10_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.02.022"},{"key":"e_1_2_10_80_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0360-2"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/2663758.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/2663758.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2022\/2663758","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:44:25Z","timestamp":1748911465000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2022\/2663758"}},"subtitle":[],"editor":[{"given":"Abdur","family":"Rauf","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":80,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1155\/2022\/2663758"],"URL":"https:\/\/doi.org\/10.1155\/2022\/2663758","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2022-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2663758"}}