https://scholars.lib.ntu.edu.tw/handle/123456789/434763
標題: | Graptopetalum paraguayense inhibits liver fibrosis by blocking TGF-β signaling in vivo and in vitro | 作者: | CHIA-CHUAN CHANG Hsu, W.-H.; Liao, S.-C.; Chyan, Y.-J.; Huang, K.-W.; Hsu, S.-L.; Chen, Y.-C.; Siu, M.-L.; Chung, Y.-S.; Huang, C.-Y.F. Chyan Y.-J. KAI-WEN HUANG Hsu S.-L. Chen Y.-C. Siu M.-L. Chang C.-C. Chung Y.-S. Huang C.-Y.F. |
公開日期: | 2019 | 卷: | 20 | 期: | 10 | 起(迄)頁: | 2592 | 來源出版物: | International Journal of Molecular Sciences | 摘要: | 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. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/434763 | DOI: | 10.3390/ijms20102592 | SDG/關鍵字: | alanine aminotransferase; aspartate aminotransferase; caspase 3; collagen type 1; collagen type 3; dimethylnitrosamine; gamma glutamyltransferase; gelatinase A; graptopetalum paraguayense extract; liver protective agent; plant extract; scleroprotein; Smad2 protein; Smad3 protein; sorafenib; sulforhodamine B; synaptophysin; unclassified drug; collagen; plant extract; scleroprotein; transforming growth factor beta; animal cell; animal experiment; animal model; animal tissue; Article; cell counting; cell invasion; cell invasion assay; cell migration; cell migration assay; cell proliferation; controlled study; down regulation; drug dose comparison; drug megadose; enzyme linked immunosorbent assay; fibrogenesis; herbal medicine; HSC-T6 cell line; human; human cell; IC50; immunohistochemistry; liver fibrosis; liver injury; liver toxicity; low drug dose; matrix assisted laser desorption ionization time of flight mass spectrometry; mitochondrial membrane potential; MTT assay; nonhuman; oxidative stress; protein expression; protein phosphorylation; rat; TGF beta signaling; Western blotting; wound healing assay; animal; cell line; chemistry; Crassulaceae; drug effect; genetics; hepatic stellate cell; liver cirrhosis; metabolism; signal transduction; Wistar rat; Animals; Cell Line; Collagen; Crassulaceae; Extracellular Matrix Proteins; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Plant Extracts; Rats; Rats, Wistar; Signal Transduction; Transforming Growth Factor beta |
顯示於: | 藥學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。