{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:25:09Z","timestamp":1787027109346,"version":"build-2736575974"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004846","name":"Beijing University of Chinese Medicine","doi-asserted-by":"publisher","award":["2021-JYB-XJSJJ055 2021-JYB-XJSJJ056"],"award-info":[{"award-number":["2021-JYB-XJSJJ055 2021-JYB-XJSJJ056"]}],"id":[{"id":"10.13039\/501100004846","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2018ZX10725505"],"award-info":[{"award-number":["2018ZX10725505"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    The Chinese traditional medicine KangXianYiAi formula (KXYA) is used to treat hepatic disease in the clinic. Here we aim to confirm the therapeutic effects and explore the pharmacological mechanisms of KXYA on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We first collected and analyzed clinical data of 40 chronic hepatitis B (CHB) patients with precancerous liver lesions under KXYA treatment. Then, the cell viability, migration, cell cycle, and apoptosis of HepAD38 cells with KXYA treatment were examined. Next, we performed network pharmacological analysis based on database mining to obtain the key target pathways and genes of KXYA treatment on HBV-related HCC. We finally analyzed the expression of the key genes between normal and HBV-related HCC tissues in databases and measured the mRNA expression of the key genes in HepAD38 cells after KXYA treatment. The KXYA treatment could reduce the liver nodule size of CHB patients, suppress the proliferation and migration capabilities, and promote apoptosis of HepAD38 cells. The key pathways of KXYA on HBV-related HCC were Cancer, Hepatitis B, Viral carcinogenesis, Focal adhesion, and\n                    <jats:italic>PI3K-Akt<\/jats:italic>\n                    signaling, and KXYA treatment could regulate the expression of the key genes including\n                    <jats:italic>HNF4A, MAPK8, NR3C1, PTEN, EGFR<\/jats:italic>\n                    , and\n                    <jats:italic>HDAC1<\/jats:italic>\n                    . The KXYA exhibited a curative effect\n                    <jats:italic>via<\/jats:italic>\n                    inhibiting proliferation, migration, and promoting apoptosis of HBV-related HCC and the pharmacological mechanism was related to the regulation of the expression of\n                    <jats:italic>HNF4A, MAPK8, NR3C1, PTEN, EGFR,<\/jats:italic>\n                    and\n                    <jats:italic>HDAC1<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.985084","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T01:17:23Z","timestamp":1662340643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Network pharmacology and in vitro experiments-based strategy to investigate the mechanisms of KangXianYiAi formula for hepatitis B virus-related hepatocellular carcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Xu","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hening","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoke","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushuo","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Zao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2019an","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1136\/gutjnl-2013-306228","article-title":"Integration of tumour and viral genomic characterizations in HBV-related hepatocellular carcinomas","volume":"64","author":"Amaddeo","year":"2015","journal-title":"Gut"},{"key":"B2","doi-asserted-by":"publisher","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.org: Online Mendelian Inheritance in Man (OMIM\u00ae), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"D36","DOI":"10.1093\/nar\/gku1055","article-title":"Gene: a gene-centered information resource at NCBI","volume":"43","author":"Brown","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"8402","DOI":"10.1038\/s41598-021-87812-9","article-title":"The mechanism of TiaoGanYiPi formula for treating chronic Hepatitis B by network pharmacology and molecular docking verification","volume":"11","author":"Cao","year":"2021","journal-title":"Sci. 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