{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T20:06:11Z","timestamp":1770753971452,"version":"3.50.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Chung Shan Medical University and Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital","award":["CSMU-TSMH-104-03"],"award-info":[{"award-number":["CSMU-TSMH-104-03"]}]},{"name":"Buddhist Tzu Chi Bioinnovation Center, Tzu Chi Foundation, Hualien, Taiwan, and Ministry of Science and Technology, Taiwan","award":["MOST 106-2320-B-303-001-MY3"],"award-info":[{"award-number":["MOST 106-2320-B-303-001-MY3"]}]},{"name":"Buddhist Tzu Chi Bioinnovation Center, Tzu Chi Foundation, Hualien, Taiwan, and Ministry of Science and Technology, Taiwan","award":["MOST 106-2320-B-303-002-MY3"],"award-info":[{"award-number":["MOST 106-2320-B-303-002-MY3"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oral submucous fibrosis (OSF) is a premalignant disorder in the oral cavity, and areca nut chewing habit has been implicated in the persistent activation of myofibroblasts and the subsequent fibrosis. Therefore, it is critical to ameliorate the excessive activities of myofibroblasts prior to the malignant transformation of OSF. In the current study, we evaluated the cytotoxicity of butylidenephthalide (BP), a major phthalide ingredient of <jats:italic>Angelica sinensis<\/jats:italic>, in fibrotic buccal mucosal fibroblasts (fBMFs) as well as various myofibroblast hallmarks, including the phenotypical characteristics and fibrosis\u2010related markers. Our results demonstrated that myofibroblast activities, including collagen gel contraction, migration, invasion and wound healing abilities were inhibited in response to BP. The expression levels of myofibroblast marker, \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), fibronectin and type 1 collagen A1 were decreased after exposure of BP. Moreover, we found that the EMT\u2010related markers, Twist, Snail and ZEB1 were all downregulated after BP treatment. Most importantly, our findings demonstrated that BP impeded the binding of Snail to the E\u2010box region in the \u03b1\u2010SMA promoter, which may lead to inhibition of the arecoline\u2010induced myofibroblast activities. Collectively, our data indicated that BP reduced numerous myofibroblast features in fBMFs and hindered the binding of Snail to \u03b1\u2010SMA, thereby may function as an effective and natural antifibrosis compound.<\/jats:p>","DOI":"10.1002\/tox.22557","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T18:24:48Z","timestamp":1523989488000},"page":"686-694","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Butylidenephthalide abrogates the myofibroblasts activation and mesenchymal transdifferentiation in oral submucous fibrosis"],"prefix":"10.1002","volume":"33","author":[{"given":"Tzu\u2010Rong","family":"Su","sequence":"first","affiliation":[{"name":"Antai Medical Care Cooperation Antai Tian\u2010Sheng Memorial Hospital Pingtung Taiwan"},{"name":"Department of beauty science Meiho University Pingtung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Wen","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Dentistry Chung Shan Medical University Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Ling","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Institute of Oral Sciences, Chung Shan Medical University Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lo\u2010Lin","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine Taipei Medical University Taipei Taiwan"},{"name":"Division of Oral and Maxillofacial Surgery, Department of Dentistry Wan Fang Hospital, Taipei Medical University Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih\u2010Yuan","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine Taipei 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