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Molecules 2015, 20(4), 6794-6807; doi:10.3390/molecules20046794

Inhibition of Tanshinone IIA, Salvianolic Acid A and Salvianolic Acid B on Areca Nut Extract-Induced Oral Submucous Fibrosis in Vitro

1
Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China
2
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 1 February 2015 / Revised: 27 March 2015 / Accepted: 8 April 2015 / Published: 15 April 2015
(This article belongs to the Section Natural Products)
View Full-Text   |   Download PDF [2269 KB, uploaded 15 April 2015]   |  

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. View Full-Text
Keywords: tanshinone IIA; salvianolic acid A; salvianolic acid B; areca nut; oral submucous fibrosis tanshinone IIA; salvianolic acid A; salvianolic acid B; areca nut; oral submucous fibrosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Dai, J.-P.; Zhu, D.-X.; Sheng, J.-T.; Chen, X.-X.; Li, W.-Z.; Wang, G.-F.; Li, K.-S.; Su, Y. Inhibition of Tanshinone IIA, Salvianolic Acid A and Salvianolic Acid B on Areca Nut Extract-Induced Oral Submucous Fibrosis in Vitro. Molecules 2015, 20, 6794-6807.

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