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Osthole (<jats:styled-content style=\"fixed-case\">OST<\/jats:styled-content>) has good therapeutic effects on liver fibrosis. Our study sought to investigate the pharmacological effects of <jats:styled-content style=\"fixed-case\">OST<\/jats:styled-content> on ferroptosis in hepatic stellate cells (<jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content>) during the development of liver fibrosis and define the mechanisms involved. The in\u00a0vivo model of liver fibrosis was established by <jats:styled-content style=\"fixed-case\">CCl<jats:sub>4<\/jats:sub><\/jats:styled-content> treatment. <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EDU<\/jats:styled-content> assays were used to assess cell viability and proliferation, respectively. The interaction between myocyte enhancer factor <jats:styled-content style=\"fixed-case\">2A<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">MEF2A<\/jats:styled-content>) and Y\u2010box binding protein 1 (<jats:styled-content style=\"fixed-case\">YBX1<\/jats:styled-content>) was analyzed by dual luciferase reporter and chromatin immunoprecipitation (<jats:styled-content style=\"fixed-case\">ChIP<\/jats:styled-content>) assays. <jats:styled-content style=\"fixed-case\">OST<\/jats:styled-content> treatment alleviated <jats:styled-content style=\"fixed-case\">CCl<jats:sub>4<\/jats:sub><\/jats:styled-content>\u2010induced liver fibrosis in mice by activating ferroptosis. <jats:styled-content style=\"fixed-case\">OST<\/jats:styled-content> induced ferroptosis in <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content> and inhibited the activation of <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content> in\u00a0vitro, while these effects of <jats:styled-content style=\"fixed-case\">OST<\/jats:styled-content> were reversed by <jats:styled-content style=\"fixed-case\">MEF2A<\/jats:styled-content> overexpression or <jats:styled-content style=\"fixed-case\">YBX1<\/jats:styled-content> overexpression. Mechanistically, <jats:styled-content style=\"fixed-case\">MEF2A<\/jats:styled-content> activated the Wnt\/\u03b2\u2010catenin signaling by transcriptionally facilitating <jats:styled-content style=\"fixed-case\">YBX1<\/jats:styled-content> expression. As expected, the inactivation of Wnt\/\u03b2\u2010catenin signaling or <jats:styled-content style=\"fixed-case\">YBX1<\/jats:styled-content> knockdown could reverse the regulatory effect of <jats:styled-content style=\"fixed-case\">MEF2A<\/jats:styled-content> upregulation on the activation of <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content> and ferroptosis in <jats:styled-content style=\"fixed-case\">OST<\/jats:styled-content>\u2010treated <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">OST<\/jats:styled-content> mitigated liver fibrosis by inducing ferroptosis in <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content> and repressing the activation of <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content> through inhibiting the <jats:styled-content style=\"fixed-case\">MEF2A<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">YBX1<\/jats:styled-content>\/Wnt\/\u03b2\u2010catenin axis.<\/jats:p>","DOI":"10.1111\/cbdd.70113","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T08:51:52Z","timestamp":1746262312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Osthole Induces Hepatic Stellate Cell Ferroptosis to Alleviate Liver Fibrosis by Inhibiting the Y\u2010Box Binding Protein 1\u2010Wnt\/\u03b2\u2010Catenin Axis Through Downregulating Myocyte Enhancer Factor <scp>2A<\/scp>"],"prefix":"10.1111","volume":"105","author":[{"given":"Ming","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Hunan Provincial People\u2018s Hospital (The First Affiliated Hospital of Hunan Normal University)  Changsha Hunan Province 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