Emodin alleviates CCl4‑induced liver fibrosis by suppressing epithelial‑mesenchymal transition and transforming growth factor‑β1 in rats

Liu,Feng; Zhang,Jing; Qian,Jianmin; Wu,Gang; Ma,Zhenyu

doi:10.3892/mmr.2018.9324

Emodin alleviates CCl4‑induced liver fibrosis by suppressing epithelial‑mesenchymal transition and transforming growth factor‑β1 in rats

Authors:
- Feng Liu
- Jing Zhang
- Jianmin Qian
- Gang Wu
- Zhenyu Ma
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Affiliations: Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Nursing Center, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
Published online on: July 26, 2018 https://doi.org/10.3892/mmr.2018.9324
Pages: 3262-3270
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver fibrosis is a chronic disease that exhibits a complicated pathophysiology. It is characterized by the deposition of the extracellular matrix. Emodin, an active constituent isolated from rhubarb, has antibacterial, immunosuppressive and anti‑inflammatory effects. In the present study, the mechanism through which emodin alleviates liver fibrosis in rats was investigated. A rat model of liver fibrosis was generated by administering CCl4 via subcutaneous injection twice a week for 12 weeks. Emodin or sodium carboxymethylcellulose (CMC), as the vehicle, were intragastrically administered daily. After 12 weeks, the liver function index was examined by blood analysis, histopathological scores of fibrosis was determined by hematoxylin and eosin staining and level of collagen deposition was examined by Masson staining. In addition, protein and RNA samples were collected for further analysis. The results of the present study revealed that emodin significantly reduced the liver function index and level of collagen deposition in a dose‑dependent manner. Furthermore, emodin reduced the expression of transforming growth factor‑β1 (TGF‑β1) and the phosphorylation levels of mothers against decapentaplegic homolog 2/3, and inhibited the CCl4‑induced downregulation of E‑cadherin and upregulation of the mesenchymal markers, fibronectin and vimentin. The expression levels of TGF‑β1, Snail family transcriptional repressor (Snail) 2, Snail, twist‑related protein 1 and zinc finger E‑box‑binding homeobox (ZEB)1 and 2 mRNA were significantly decreased in emodin‑treated groups compared with the untreated control. Collectively, the results of the present study suggested that emodin may exert antifibrotic effects via the suppression of TGF‑β1 signaling and epithelial‑mesenchymal transition.

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