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.
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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)
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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
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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)
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