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proved to be pivotal in hepatic fibrosis. Therefore, the suppression of HSC activation is an effective anti-fibrotic strategy. Although studies have indicated that eupatilin, a bioactive flavone found in Artemisia argyi, has anti-fibrotic properties, the effect of eupatilin on hepatic fibrosis is currently unclear. In this study, we used the human hepatic stellate cell line LX-2 and the classical CCl4-induced hepatic fibrosis mouse model for in vitro and vivo experiments. We found that eupatilin significantly repressed the levels of the fibrotic markers COL1\u03b11 and \u03b1-SMA, as well as other collagens in LX-2 cells. Meanwhile, eupatilin markedly inhibited LX-2 cell proliferation, as verified by the reduced cell viability and down-regulation of c-Myc, cyclinB1, cyclinD1, and CDK6. Additionally, eupatilin decreased the level of PAI-1 in a dose-dependent manner, and knockdown of PAI-1 using PAI-1-specific shRNA significantly suppressed the levels of COL1\u03b11, \u03b1-SMA, and the epithelial\u2013mesenchymal transition (EMT) marker N-cadherin in LX-2 cells. Western blotting indicated that eupatilin reduced the protein level of \u03b2-catenin and its nuclear translocation, while the transcript level of \u03b2-catenin was not affected in LX-2 cells. Furthermore, analysis of histopathological changes in the liver and markers of liver function and fibrosis revealed that hepatic fibrosis in CCl4-treated mice was markedly alleviated by eupatilin. In conclusion, eupatilin ameliorates hepatic fibrosis and hepatic stellate cell activation by suppressing the \u03b2-catenin\/PAI-1 pathway.<\/jats:p>","DOI":"10.3390\/ijms24065933","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T06:56:48Z","timestamp":1679381808000},"page":"5933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Eupatilin Ameliorates Hepatic Fibrosis and Hepatic Stellate Cell Activation by Suppressing \u03b2-catenin\/PAI-1 Pathway"],"prefix":"10.3390","volume":"24","author":[{"given":"Jinyuan","family":"Hu","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Pan","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuekuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Traditional Chinese Medicine, Chongqing College of Traditional Chinese Medicine, Chongqing 402760, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Traditional Chinese Medicine, Chongqing College of Traditional Chinese Medicine, Chongqing 402760, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfu","family":"Cao","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Traditional Chinese Medicine, Chongqing College of Traditional Chinese Medicine, Chongqing 402760, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. 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