Asiatic acid inhibits liver fibrosis by blocking TGF-beta/Smad signaling in vivo and in vitro

Liver fibrosis is a major cause of liver failure, but treatment remains ineffective. In the present study, we investigated the mechanisms and anti-hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl(4)) and in vitro in TGF-beta1-stimul...

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Veröffentlicht in:	PloS one 2012-02, Vol.7 (2), p.e31350
Hauptverfasser:	Tang, Li-xia, He, Rui-hua, Yang, Guang, Tan, Jia-ju, Zhou, Li, Meng, Xiao-ming, Huang, Xiao Ru, Lan, Hui Yao
Format:	Artikel
Sprache:	eng
Schlagworte:	Acids Actin Animals Antigens Antioxidants Biology Blotting, Western Bone morphogenetic proteins Carbon Tetrachloride Cell activation Cell Line Chemical compounds Collagen Collagen Type I - metabolism Computational Biology Connective tissue growth factor Cytotoxicity Disease control Dosage Drug dosages Fibroblasts Fibrosis Gastroenterology and Hepatology Gene Knockdown Techniques Genetics and Genomics Health aspects Health sciences Hepatic Stellate Cells - drug effects Hepatic Stellate Cells - metabolism Hepatic Stellate Cells - pathology Hospitals Immunohistochemistry Inhibition Laboratory animals Liver Liver - drug effects Liver - metabolism Liver - pathology Liver - physiopathology Liver Cirrhosis - metabolism Liver Cirrhosis - pathology Liver Cirrhosis - physiopathology Liver Cirrhosis - prevention & control Liver diseases Liver Function Tests Male Medical research Medicine Microwaves Molecular Biology Pentacyclic Triterpenes - pharmacology Pentacyclic Triterpenes - therapeutic use Pharmacology Phosphorylation - drug effects Rats Rats, Sprague-Dawley Real-Time Polymerase Chain Reaction Rodents Signal Transduction - drug effects Smad protein Smad Proteins - metabolism Smad2 protein Smad7 protein Smooth muscle Studies Time Factors Transformation Transforming Growth Factor beta - metabolism Transforming Growth Factor beta - pharmacology Transforming growth factor-b Transforming growth factors Up-Regulation - drug effects
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Zusammenfassung:	Liver fibrosis is a major cause of liver failure, but treatment remains ineffective. In the present study, we investigated the mechanisms and anti-hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl(4)) and in vitro in TGF-beta1-stimulated rat hepatic stellate cell line (HSC-T6). Treatment with AA significantly attenuated CCl(4)-induced liver fibrosis and functional impairment in a dosage-dependent manner, including blockade of the activation of HSC as determined by inhibiting de novo alpha smooth muscle actin (a-SMA) and collagen matrix expression, and an increase in ALT and AST (all p
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0031350