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Open Access Research article

Dissection of the mechanism of traditional Chinese medical prescription-Yiqihuoxue formula as an effective anti-fibrotic treatment for systemic sclerosis

Ting Wu1, Haiyan Chu1, Wenzhen Tu26, Mengmeng Song3, Dongdong Chen2, Jin Yuan3, Ling Yu2, Yanyun Ma1, Qingmei Liu1, Li Jin1, Xiaodong Zhou46, Hejian Zou356, Wenyu Wu3567* and Jiucun Wang156*

Author Affiliations

1 National Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, PR China

2 Department of Dermatology, Shanghai TCM-integrated Hospital, Shanghai, PR China

3 Huashan Hospital, Shanghai, PR China

4 Division of Rheumatology, University of Texas-Houston Health Science Center, Houston, USA

5 Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, PR China

6 International Network of Scleroderma Clinical Care and Research (InSCAR), Shanghai, PR China

7 Department of Dermatology, Huashan Hospital, Shanghai, PR China

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BMC Complementary and Alternative Medicine 2014, 14:224  doi:10.1186/1472-6882-14-224

Published: 7 July 2014

Abstract

Background

Systemic sclerosis (SSc) is a connective tissue fibrotic disease for which there is no effective treatment. Traditional Chinese Medicine (TCM), such as the Yiqihuoxue formula used in Shanghai TCM-integrated Hospital, has shown the efficacy of anti-fibrosis in clinical applications. This study was aiming to dissect the anti-fibrotic mechanism of Yiqihuoxue treatment for SSc.

Methods

Bleomycin-induced mice and SSc dermal fibroblasts were treated with Yiqihuoxue decoction; NIH-3T3 fibroblasts were exposed to exogenous TGF-β1, and then cultured with or without Yiqihuoxue decoction. Luciferase reporter gene assay was used to determine the activity of Smad binding element (SBE). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the mRNA levels of extracellular matrix (ECM) genes. The protein levels of type I collagen, Smad3 and phosphorylated-Smad3 (p-Smad3) were detected by western blotting. Student’s t-tests were used to determine the significance of the results.

Results

Bleomycin-induced mice, SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts showed higher levels of ECM gene transcriptions and collagen production. In addition, the phosphorylation level of Smad3 and activity of SBE were significantly increased after exogenous TGF-β1 induction. Whereas, Yiqihuoxue treatment could obviously attenuate fibrosis in bleomycin-induced mice, down regulate ECM gene expressions and collagen production in SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts. Furthermore, the aberrantly high phosphorylation level of Smad3 and activity of SBE in the TGF-β1-induced NIH/3T3 fibroblasts were also dramatically decreased by Yiqihuoxue treatment.

Conclusions

Yiqihuoxue treatment could effectively reduce collagen production via down-regulating the phosphorylation of Smad3 and then the activity of SBE, which are involved in the TGF-β pathway and constitutively activated in the progression of SSc.

Keywords:
Systemic sclerosis; Traditional Chinese Medicine; Fibrosis; Collagen; TGF-β