{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:28:33Z","timestamp":1788571713945,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Primary liver cancer (PLC), mainly hepatocellular carcinoma (HCC), remains a leading global cause of cancer mortality. Metabolic dysregulation is a hallmark of HCC progression. Sophoricoside (SOP), a flavonoid glycoside from Sophora japonica, exhibits anti\u2010inflammatory and metabolic regulatory activities, yet its role in liver cancer is unclear. Here, we investigated the antitumor effects and underlying mechanisms of SOP in HCC. Huh7 and HepG2 cells were treated with increasing SOP concentrations to assess proliferation, migration, and invasion using CCK\u20108, colony formation, wound\u2010healing, and Transwell assays. Transcriptomic profiling (RNA\u2010seq) and pathway enrichment analyses were conducted, followed by RT\u2010qPCR and Western blot validation. In vivo efficacy was evaluated in Huh7 xenografts (160\u2009mg\/kg, daily for 27 days). SOP inhibited proliferation in a dose\u2010dependent manner (IC\u2085\u2080\u2009\u2248\u2009320\u2009\u03bcM), reducing clonogenicity by ~65% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01) and suppressing migration and invasion by 60%\u201370%. These effects correlated with decreased PCNA, Cyclin D1, and N\u2010cadherin, and upregulated E\u2010cadherin. RNA\u2010seq revealed 1263 differentially expressed genes, with AMPK pathway activation and repression of G2M, E2F, and MYC signaling. SOP increased AMPK phosphorylation (Thr172; +2.5\u2010fold at 300\u2009\u03bcM) without affecting total AMPK. In vivo, SOP reduced tumor volume by ~60% and Ki67 expression while sustaining AMPK activation. Co\u2010treatment with the AMPK inhibitor compound C abrogated these effects, confirming AMPK dependence. Collectively, SOP functions as a natural AMPK agonist that reprograms tumor metabolism and suppresses oncogenic signaling, highlighting its promise as a low\u2010toxicity therapeutic candidate for liver cancer.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70838","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:31:24Z","timestamp":1776663084000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Activation of AMPK by Sophoricoside Suppresses Primary Liver Cancer Progression In Vitro and In Vivo"],"prefix":"10.1002","volume":"40","author":[{"given":"Jian\u2010Zhong","family":"Wang","sequence":"first","affiliation":[{"name":"Suzhou Medical College Soochow University Suzhou Jiangsu China"},{"name":"Department of General Surgery First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Ruijin People's Hospital Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8150-5964","authenticated-orcid":false,"given":"Teng\u2010Fei","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Huanggang Central Hospital Yangtze University Huanggang Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1131-0958","authenticated-orcid":false,"given":"Hong\u2010Fu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.3055"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx030"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyaf017"},{"issue":"23","key":"e_1_2_12_6_1","first-page":"2498","article-title":"Sorafenib in Advanced Hepatocellular Carcinoma","volume":"359","author":"Palmer D. 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