Graptopetalum paraguayense Inhibits Liver Fibrosis by Blocking TGF-β Signaling In Vivo and In Vitro
by
Wei-Hsiang Hsu 1,†
, Se-Chun Liao 2,†, Yau-Jan Chyan 3,†, Kai-Wen Huang 4, Shih-Lan Hsu 5, Yi-Chen Chen 1, Ma-Li Siu 3, Chia-Chuan Chang 6, Yuh-Shan Chung 3 and Chi-Ying F. Huang 1,2,*
Wei-Hsiang Hsu 1,†, Se-Chun Liao 2,†, Yau-Jan Chyan 3,†, Kai-Wen Huang 4, Shih-Lan Hsu 5, Yi-Chen Chen 1, Ma-Li Siu 3, Chia-Chuan Chang 6, Yuh-Shan Chung 3 and Chi-Ying F. Huang 1,2,*
1
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan
2
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
3
Development of Natural Resource, Institute of Pharmaceutics, Development Center for Biotechnology (DCB), Taipei 11571, Taiwan
4
Department of Surgery & Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University, Taipei 10051, Taiwan
5
Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan
6
Department of Pharmacy, School of Pharmacy, National Taiwan University, Taipei 10050, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this study.
Int. J. Mol. Sci. 2019, 20(10), 2592; https://doi.org/10.3390/ijms20102592
Received: 19 April 2019 / Revised: 16 May 2019 / Accepted: 24 May 2019 / Published: 27 May 2019
(This article belongs to the Special Issue TGF-Beta Super Family Signaling 2.0)
Background and Aims: Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, which occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension. Activated hepatic perivascular stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines, such as TGF-β1. The inhibition of TGF-β1 function or synthesis is a major target for the development of antifibrotic therapies. Our previous study showed that the water and ethanol extracts of Graptopetalum paraguayense (GP), a Chinese herbal medicine, can prevent dimethylnitrosamine (DMN)-induced hepatic inflammation and fibrosis in rats. Methods: We used rat hepatic stellate HSC-T6 cells and a diethylnitrosamine (DEN)-induced rat liver injury model to test the potential mechanism of GP extracts and its fraction, HH-F3. Results: We demonstrated that GP extracts and HH-F3 downregulated the expression levels of extracellular matrix (ECM) proteins and inhibited the proliferation and migration via suppression of the TGF-β1 pathway in rat hepatic stellate HSC-T6 cells. Moreover, the HH-F3 fraction decreased hepatic collagen content and reduced plasma AST, ALT, and γ-GT activities in a DEN-induced rat liver injury model, suggesting that GP/HH-F3 has hepatoprotective effects against DEN-induced liver fibrosis. Conclusion: These findings indicate that GP/HH-F3 may be a potential therapeutic agent for the treatment of liver fibrosis. The inhibition of TGF-β-mediated fibrogenesis may be a central mechanism by which GP/HH-F3 protects the liver from injury.
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MDPI and ACS Style
Hsu, W.-H.; Liao, S.-C.; Chyan, Y.-J.; Huang, K.-W.; Hsu, S.-L.; Chen, Y.-C.; Siu, M.-L.; Chang, C.-C.; Chung, Y.-S.; Huang, C.-Y.F. Graptopetalum paraguayense Inhibits Liver Fibrosis by Blocking TGF-β Signaling In Vivo and In Vitro. Int. J. Mol. Sci. 2019, 20, 2592.
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