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

Molecules

Jian-Ping Dai²  Dan-Xia Zhu²  Jiang-Tao Sheng²  Xiao-Xuan Chen²  Wei-Zhong Li¹  Ge-Fei Wang²  Kang-Sheng Li²  Yun Su² 

[1] Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA; E-Mail:;Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China; E-Mails:

关键词: tanshinone IIA1;    salvianolic acid A;    salvianolic acid B;    areca nut;    oral submucous fibrosis;   

DOI  :  10.3390/molecules20046794

来源: mdpi

【 摘 要 】

Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA1 (Tan-IIA1), 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-IIA1, 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-IIA1, 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-IIA1, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.