title: Inhibition of Tanshinone IIA, salvianolic acid A and salvianolic acid B on Areca nut extract-induced oral submucous fibrosis in vitro.
abstract: 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-β/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-β1, IL-6 and TNF-α; 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-β/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.
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China. daijpedu2008@163.com.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Dai
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China. scorpion37@126.com.
authors.forename: Dan-Xia
authors.initials: DX
authors.lastname: Zhu
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China. shengjt@126.com.
authors.forename: Jiang-Tao
authors.initials: JT
authors.lastname: Sheng
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China. chen.x.x.85@163.com.
authors.forename: Xiao-Xuan
authors.initials: XX
authors.lastname: Chen
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA. wzlistdxedu@sina.cn.
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China. gfwangstdx@sina.cn.
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China. liksedustdx@163.com.
authors.forename: Kang-Sheng
authors.initials: KS
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China. yunsu1978@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Su
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D001114:Areca / Q000737:chemistry*; D001572:Benzofurans / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007773:Lactates / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009754:Nuts / Q000737:chemistry*; D009914:Oral Submucous Fibrosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D053147:Plant Exudates / Q000009:adverse effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053630:Depsides
chemical_list: D045784:Abietanes; D001572:Benzofurans; D002109:Caffeic Acids; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D007773:Lactates; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053147:Plant Exudates; D051057:Proto-Oncogene Proteins c-akt; D051785:Smad Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D016212:Transforming Growth Factor beta; C021751:tanshinone; C066201:salvianolic acid A; C076944:salvianolic acid B; D053630:Depsides