{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:39:02Z","timestamp":1785368342175,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Nonalcoholic steatohepatitis (NASH) is an increasingly common chronic liver disease in which hepatic fibrosis is the major pathological change. The transforming growth factor \u03b2 (TGF\u2010\u03b2)\/mall mothers against decapentaplegic (Smad) signaling is the main effector of fibrosis. Although the antifibrotic effect of echinacoside (Ech) on the liver has been indicated previously, the cellular and molecular mechanisms remain unclear. This study aims to investigate both in vivo and in vitro antifibrotic properties of Ech.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Cell viability and scratch\/wound assays show that Ech significantly inhibits the proliferation, migration, and activation of human hepatic stellate LX\u20102 cells. In mice with high\u2010fat diet\u2010induced hepatic fibrosis, Ech treatment attenuates the progression of liver injury, inflammation, and fibrosis. Furthermore, transcriptome analysis and subsequent functional validation demonstrate that Ech achieves antifibrotic effects by the activin receptor type\u20102A (ACVR2A)\u2010mediated TGF\u2010\u03b21\/Smad signaling pathway; ultimately, ACVR2A is demonstrated to be an important target for hepatic fibrosis by inhibiting and inducing the expression of <jats:italic>ACVR2A<\/jats:italic> in LX\u20102 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ech exerts potent antifibrotic effects by inhibiting the ACVR2A\u2010mediated TGF\u2010\u03b21\/Smad signaling axis and may serve as an alternative treatment for hepatic fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202300553","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T11:40:08Z","timestamp":1708170008000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Echinacoside Exerts Antihepatic Fibrosis Effects in High\u2010Fat Mice Model by Modulating the ACVR2A\u2010Smad Pathway"],"prefix":"10.1002","volume":"68","author":[{"given":"Jie","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Medicine Linfen Vocational and Technical College  Linfen Shanxi 041000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglei","family":"Xu","sequence":"additional","affiliation":[{"name":"Medical Security Center The No. 983th Hospital of Joint Logistics Support Forces of Chinese PLA  Tianjin 300142 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingfang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University  Shanghai 201700 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-1490","authenticated-orcid":false,"given":"Liyan","family":"Xiong","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00365-6"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10020346"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.04.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23838"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.5370"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154925"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.10.026"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00366-5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13665"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25496"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6762"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2014.10.014"},{"key":"e_1_2_10_13_1","first-page":"279","volume":"42","author":"Zhang H.","year":"2018","journal-title":"Int. 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