{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:52:03Z","timestamp":1785243123587,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T00:00:00Z","timestamp":1429056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the national natural science foundation of china","doi-asserted-by":"publisher","award":["No.81374040"],"award-info":[{"award-number":["No.81374040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the national natural science foundation of china","doi-asserted-by":"publisher","award":["No. 81001322"],"award-info":[{"award-number":["No. 81001322"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the national natural science foundation of china","doi-asserted-by":"publisher","award":["No.81001340"],"award-info":[{"award-number":["No.81001340"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE)-induced oral submucous fibrosis (OSF) in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2\/-9 activity, MMP-1\/-13 and TIMP-1\/-2 expression, cytokine secretion and the activation of PI3K\/AKT, ERK\/JNK\/p38 MAPK and TGF-\u03b2\/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs), inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2\/-9 activity, decrease TIMP-1\/-2 expression and inhibit the transcription and release of CTGF, TGF-\u03b21, IL-6 and TNF-\u03b1; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-\u03b2\/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.<\/jats:p>","DOI":"10.3390\/molecules20046794","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T10:51:24Z","timestamp":1429095084000},"page":"6794-6807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Inhibition of Tanshinone IIA, Salvianolic Acid A and Salvianolic Acid B on Areca Nut Extract-Induced Oral Submucous Fibrosis in Vitro"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8304-8207","authenticated-orcid":false,"given":"Jian-Ping","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College,  Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-Xia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College,  Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Tao","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College,  Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College,  Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Zhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge-Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College,  Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Sheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College,  Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College,  Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,4,15]]},"reference":[{"key":"ref_1","unstructured":"IARC (2004). 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