{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:04:33Z","timestamp":1790546673349,"version":"4.1.0"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1G1A1004280"],"award-info":[{"award-number":["2020R1G1A1004280"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Daejeon St. Mary\u2019s Hospital","award":["CMCDJ-P-2019-003"],"award-info":[{"award-number":["CMCDJ-P-2019-003"]}]},{"DOI":"10.13039\/501100002648","name":"The Catholic University of Korea","doi-asserted-by":"crossref","award":["5-2020-B0001-00260"],"award-info":[{"award-number":["5-2020-B0001-00260"]}],"id":[{"id":"10.13039\/501100002648","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Vocal fold scarring is a major cause of dysphonia. Vocal fold fibroblasts (VFFs) and the TGF-\u03b2 signaling pathway play important roles in scar formation. Eupatilin, a chromone derivative of the <jats:italic>Artemisia<\/jats:italic> species, is a traditional folk remedy for wound healing. However, until recently, few studies investigated the therapeutic effects of eupatilin. We investigated the antifibrogenic effects of eupatilin on TGF-\u03b21-treated human vocal fold fibroblasts (hVFFs). The optimal concentration of eupatilin was determined by a cell viability assay. Western blotting was used to measure the expression of alpha-smooth muscle actin during myofibroblast differentiation, fibronectin (FN), collagen type I (Col I), and collagen type III (Col III) extracellular matrix proteins, and Smad2, Smad3, and p38 in the fibrotic pathway. Measurements were made before and after eupatilin treatment. Eupatilin at 100 nM was shown to be safe for use in hVFFs. TGF-\u03b21 induced hVFFs to proliferate and differentiate into myofibroblasts and increased Col III and FN synthesis in a time- and dose-dependent manner. Eupatilin suppressed TGF-\u03b21-induced hVFF proliferation and differentiation into myofibroblasts through the Smad and p38 signaling pathways. Furthermore, eupatilin inhibited TGF-\u03b21-induced FN, Col I, and Col III synthesis in hVFFs. Our <jats:italic>in vitro<\/jats:italic> findings show that eupatilin effectively suppressed TGF-\u03b21-induced fibrotic changes in hVFFs via the Smad and p38 signaling pathways. Thus, eupatilin may be considered a novel therapeutic agent for the treatment of vocal fold fibrosis.<\/jats:p>","DOI":"10.1371\/journal.pone.0249041","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T20:09:00Z","timestamp":1616702940000},"page":"e0249041","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antifibrotic effects of eupatilin on TGF-\u03b21-treated human vocal fold fibroblasts"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6370-5997","authenticated-orcid":true,"given":"Sung Joon","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsu","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Heon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9551-9571","authenticated-orcid":true,"given":"Choung-Soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"issue":"3","key":"pone.0249041.ref001","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1177\/000348940911800310","article-title":"Effects of transforming growth factor-beta1 on human vocal fold fibroblasts","volume":"118","author":"RC Branski","year":"2009","journal-title":"Ann Otol Rhinol Laryngol"},{"issue":"10","key":"pone.0249041.ref002","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/lary.24723","article-title":"Smad3: an emerging target for vocal fold fibrosis","volume":"124","author":"BC 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