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: Jian-Ping Dai, Dan-Xia Zhu, Jiang-Tao Sheng, Xiao-Xuan Chen, Wei-Zhong Li, Ge-Fei Wang, Kang-Sheng Li, Yun Su
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 20 Issue 4 Pg. 6794-807 (Apr 15 2015) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 25884554 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Abietanes
• Benzofurans
• Caffeic Acids
• Lactates
• Plant Exudates
• Smad Proteins
• Tissue Inhibitor of Metalloproteinase-1
• Transforming Growth Factor beta
• tanshinone
• Tissue Inhibitor of Metalloproteinase-2
• salvianolic acid A
• Collagen
• salvianolic acid B
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Abietanes (pharmacology)
• Animals
• Areca (chemistry)
• Benzofurans (pharmacology)
• Caffeic Acids (pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Collagen (genetics, metabolism)
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (drug effects, metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• In Vitro Techniques
• Lactates (pharmacology)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Nuts (chemistry)
• Oral Submucous Fibrosis (drug therapy, etiology, metabolism)
• Plant Exudates (adverse effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Smad Proteins (metabolism)
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)
• Tissue Inhibitor of Metalloproteinase-2 (genetics, metabolism)
• Transforming Growth Factor beta (biosynthesis)