{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:36Z","timestamp":1787027856898,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council of Taiwan","award":["MOST104-2314-B-037-059-MY2"],"award-info":[{"award-number":["MOST104-2314-B-037-059-MY2"]}]},{"name":"National Science and Technology Council of Taiwan","award":["KMU-TC112A02"],"award-info":[{"award-number":["KMU-TC112A02"]}]},{"name":"Regenerative Medicine and Cell Therapy Research Center of Kaohsiung Medical University","award":["MOST104-2314-B-037-059-MY2"],"award-info":[{"award-number":["MOST104-2314-B-037-059-MY2"]}]},{"name":"Regenerative Medicine and Cell Therapy Research Center of Kaohsiung Medical University","award":["KMU-TC112A02"],"award-info":[{"award-number":["KMU-TC112A02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Oral submucous fibrosis (OSMF) is a chronic inflammatory disease and a potentially malignant oral disorder, characterized by fibrosis of the oral mucosa. TGF-\u03b2 signaling pathways have been implicated in the development of OSMF, with areca nut extract (ANE) contributing to the disease progression. Simvastatin, a statin drug, has demonstrated anti-fibrotic properties in various fibrotic conditions. However, its therapeutic potential in treating OSMF remains unclear. In this study, 8-week-old male BALB\/c mice were randomly divided into three groups based on different time points. Each mouse was then treated with four different drug formulations. Post-treatment, specimens were collected for histopathological examination and staining to assess skin thickness, fibrosis, and collagen deposition. ANE treatment alone significantly increased skin thickness and collagen deposition compared to the control group after the 4-week time point. The combined administration of ANE and simvastatin, resulted in a notable reduction in skin thickness and collagen deposition. Western blot analysis revealed that simvastatin effectively suppressed the expression of fibrosis-related proteins, including CTGF, and \u03b1-SMA, in ANE-induced subdermal fibrosis. These results suggest that simvastatin has potential therapeutic effects on ANE-induced subdermal fibrosis, providing a foundation for future studies and possible clinical applications.<\/jats:p>","DOI":"10.3390\/cimb45110542","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T11:18:52Z","timestamp":1698405532000},"page":"8622-8632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Simvastatin Attenuates Areca Nut Extract-Induced Subdermal Fibrosis in Mice by Targeting TGF-\u03b2 Signaling Pathways"],"prefix":"10.3390","volume":"45","author":[{"given":"Chi-Hua","family":"Chang","sequence":"first","affiliation":[{"name":"Division of Oral and Maxillofacial Surgery, Department of Dentistry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Ping","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Department of Dentistry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuk-Kwan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Division of Oral Pathology and Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Oral & Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Fang","family":"Hsiao","sequence":"additional","affiliation":[{"name":"College of Medicine, Orthopaedic Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8161-7472","authenticated-orcid":false,"given":"Yan-Hsiung","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"College of Medicine, Orthopaedic Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shih, Y.H., Wang, T.H., Shieh, T.M., and Tseng, Y.H. 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