{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:07:10Z","timestamp":1760123230151,"version":"3.41.2"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Ethnopharmacological relevance:<\/jats:bold> Hepatic fibrosis (HF) occurs in response to chronic liver injury and may easily develop into irreversible liver cirrhosis or even liver cancer. <jats:italic>Amydrium hainanense<\/jats:italic> water extract (AHWE) is a water-soluble component extracted from the Yao medicine <jats:italic>Amydrium hainanense<\/jats:italic> (H.Li, Y.Shiao &amp;amp; S.L.Tseng) H.Li, which is commonly used for treating inflammatory diseases in folk. Previous evidence suggested that AHWE significantly inhibited hepatic stellate cell activation. However, little is known regarding the therapeutic effect of AHWE in HF and its underlying action mechanism.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> Investigation of the therapeutic effect of AHWE in HF and its underlying mechanism.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The therapeutic effect of AHWE was tested <jats:italic>in vivo<\/jats:italic> using an HF mouse model <jats:italic>via<\/jats:italic> an intraperitoneal injection of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>). Histological evaluation of liver injury and fibrosis were tested by H&amp;amp;E staining and Masson\u2019s trichrome staining. Serum levels of ALT, AST, collagen type I (Col I), and hydroxyproline (HYP) were measured. The mRNA expression of liver fibrotic and inflammatory genes were tested, and the protein levels of alpha smooth muscle actin (\u03b1-SMA) and signal transducers and activators of transcription 3 (STAT3) were analyzed. The <jats:italic>in vitro<\/jats:italic> experiments were conducted using HSC-T6 and RAW264.7 cell lines.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Treatment with AHWE significantly reversed histopathological liver damage and liver function abnormalities in CCl<jats:sub>4<\/jats:sub> mouse model. Also, the serum levels of ALT, AST, Col I, and HYP in CCl<jats:sub>4<\/jats:sub>-induced HF mice were improved in AHWE treatment. Further, AHWE showed a remarkable inhibitory effect on the expression of fibrosis markers (<jats:italic>Acta2<\/jats:italic>, <jats:italic>Col1a1<\/jats:italic>, and <jats:italic>Col3a1<\/jats:italic>) and inflammatory factors (<jats:italic>Stat3, Tnfa<\/jats:italic>, <jats:italic>Il6<\/jats:italic>, and <jats:italic>Il1b<\/jats:italic>) induced by CCl<jats:sub>4<\/jats:sub>. The results of <jats:italic>in vitro<\/jats:italic> experiments were consistent with those obtained <jats:italic>in vivo<\/jats:italic>. In addition, it is shown that STAT3 signaling was involved in the anti-fibrotic effects of AHWE as evidenced by STAT3 overexpression.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The present study proposed a novel ethnomedicine for HF and suggested the underlying role of STAT3 signaling pathway regulation in this anti-fibrotic effect of the proposed medicine. These findings would serve as solid scientific evidence in support of the development of AHWE as a novel alternative or complementary therapy for HF prevention and treatment.<\/jats:p>","DOI":"10.3389\/fphar.2022.1043022","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T08:28:49Z","timestamp":1671006529000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Yao medicine Amydrium hainanense suppresses hepatic fibrosis by repressing hepatic stellate cell activation via STAT3 signaling"],"prefix":"10.3389","volume":"13","author":[{"given":"Bingmin","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yange","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lishan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaogui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guifang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1093\/toxsci\/kfq009","article-title":"Mechanisms of immune-mediated liver injury","volume":"115","author":"Adams","year":"2010","journal-title":"Toxicol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/j.1524-475X.2008.00410.x","article-title":"Growth factors and cytokines in wound healing","volume":"16","author":"Barrientos","year":"2008","journal-title":"Wound Repair Regen."},{"key":"B3","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3390\/cells9010188","article-title":"Are liver pericytes just precursors of myofibroblasts in hepatic diseases? Insights from the crosstalk between perivascular and inflammatory cells in liver injury and repair","volume":"9","author":"da Silva Meirelles","year":"2020","journal-title":"Cells"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.3390\/cells8111419","article-title":"TGF-Beta in hepatic stellate cell activation and liver fibrogenesis-updated 2019","volume":"8","author":"Dewidar","year":"2019","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","first-page":"112281","DOI":"10.1016\/j.biopha.2021.112281","article-title":"JQ-1 ameliorates schistosomiasis liver fibrosis by suppressing JAK2 and STAT3 activation","volume":"144","author":"Ding","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"125937","DOI":"10.1016\/j.foodchem.2019.125937","article-title":"Analysis of heterocyclic aromatic amine profiles in Chinese traditional bacon and sausage based on ultrahigh-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS)","volume":"310","author":"Dong","year":"2020","journal-title":"Food Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cytogfr.2016.05.001","article-title":"STAT3 signaling in immunity","volume":"31","author":"Hillmer","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1177\/1947601910397187","article-title":"Jak\/STAT pathways in cytokine signaling and myeloproliferative disorders: Approaches for targeted therapies","volume":"1","author":"Jatiani","year":"2010","journal-title":"Genes Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.str.2005.04.010","article-title":"Structural basis of FFAT motif-mediated ER targeting","volume":"13","author":"Kaiser","year":"2005","journal-title":"Structure"},{"key":"B10","doi-asserted-by":"publisher","first-page":"6008","DOI":"10.3390\/ijms20236008","article-title":"Cytokines in inflammatory disease","volume":"20","author":"Kany","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"320","DOI":"10.3904\/kjim.2018.214","article-title":"Immunological measurement of aspartate\/alanine aminotransferase in predicting liver fibrosis and inflammation","volume":"35","author":"Kim","year":"2020","journal-title":"Korean J. Intern. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.jtcme.2017.07.002","article-title":"Herbal remedies for liver fibrosis: A review on the mode of action of fifty herbs","volume":"8","author":"Latief","year":"2018","journal-title":"J. Tradit. Complement. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","article-title":"Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues","volume":"65","author":"Parola","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1089\/lrb.2017.0074","article-title":"Biomarkers associated with lymphedema and fibrosis in patients with cancer of the head and neck","volume":"16","author":"Ridner","year":"2018","journal-title":"Lymphat. Res. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3748\/wjg.v26.i2.109","article-title":"Inflammation and fibrosis in chronic liver diseases including non-alcoholic fatty liver disease and hepatitis C","volume":"26","author":"Tanwar","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10741-018-9720-1","article-title":"Biomarkers for the identification of cardiac fibroblast and myofibroblast cells","volume":"24","author":"Tarbit","year":"2019","journal-title":"Heart fail. Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"S15","DOI":"10.1016\/j.jhep.2015.02.039","article-title":"Hepatic fibrosis: Concept to treatment","volume":"62","author":"Trautwein","year":"2015","journal-title":"J. Hepatol."},{"key":"B18","doi-asserted-by":"publisher","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. Rev. Gastroenterol. Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/apt.15773","article-title":"Review article: The signalling and functional role of the extracellular matrix in the development of liver fibrosis","volume":"52","author":"Villesen","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1038\/s41374-018-0127-3","article-title":"The STAT3 inhibitor S3I-201 suppresses fibrogenesis and angiogenesis in liver fibrosis","volume":"98","author":"Wang","year":"2018","journal-title":"Lab. Invest."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.14336\/AD.2019.0116","article-title":"Pyroptosis in liver disease: New insights into disease mechanisms","volume":"10","author":"Wu","year":"2019","journal-title":"Aging Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1038\/nm.2807","article-title":"Mechanisms of fibrosis: Therapeutic translation for fibrotic disease","volume":"18","author":"Wynn","year":"2012","journal-title":"Nat. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1136\/gutjnl-2016-313392","article-title":"The HLF\/IL-6\/STAT3 feedforward circuit drives hepatic stellate cell activation to promote liver fibrosis","volume":"67","author":"Xiang","year":"2018","journal-title":"Gut"},{"key":"B24","doi-asserted-by":"publisher","first-page":"15699","DOI":"10.1021\/acs.jafc.1c06596","article-title":"Comprehensive betalain profiling of djulis (Chenopodium formosanum) cultivars using HPLC-Q-orbitrap high-resolution mass spectrometry","volume":"69","author":"Xie","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1016\/j.bbadis.2014.07.025","article-title":"Stat3 signaling activation crosslinking of TGF-\u03b21 in hepatic stellate cell exacerbates liver injury and fibrosis","volume":"1842","author":"Xu","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"B26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s40139-015-0093-z","article-title":"TNF\u03b1 in liver fibrosis","volume":"3","author":"Yang","year":"2015","journal-title":"Curr. Pathobiol. Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STATs in cancer inflammation and immunity: A leading role for STAT3","volume":"9","author":"Yu","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"B28","doi-asserted-by":"publisher","first-page":"174043","DOI":"10.1016\/j.ejphar.2021.174043","article-title":"Phillygenin inhibited LPS-induced RAW 264.7\u00a0cell inflammation by NF-\u03baB pathway","volume":"899","author":"Zhou","year":"2021","journal-title":"Eur. J. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1043022\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T08:28:52Z","timestamp":1671006532000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1043022\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":28,"alternative-id":["10.3389\/fphar.2022.1043022"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.1043022","relation":{},"ISSN":["1663-9812"],"issn-type":[{"type":"electronic","value":"1663-9812"}],"subject":[],"published":{"date-parts":[[2022,12,14]]},"article-number":"1043022"}}