| Ursolic acid ameliorates hepatic fibrosis in the rat by specific induction of apoptosis in hepatic stellate cells. | |
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MedLine Citation:
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PMID: 21168456 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background and Aims: Specific induction of cell death in activated hepatic stellate cells (hscs) is a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the cell-killing effect of ursolic acid (UA), a pentacyclic triterpenoid, in activated hscs both in vitro and in vivo. Methods: Culture-activated rat HSCs were treated with UA (0-40 μM), and the mechanisms of cell death were evaluated. The cell killing effect of UA on activated HSCs in rats chronically treated with thioacetamide (TAA) was detected by dual staining of TdT-mediated dUTP nick-end labeling (TUNEL) and smooth muscle α-actin (αSMA) immunohistochemistry, and resolution of hepatic fibrosis was evaluated. Further, the protective effects of UA on progression of hepatic fibrosis caused by TAA and bile duct ligation (BDL) were evaluated. Results: UA induced apoptotic cell death in culture-activated hscs, but not in isolated hepatocytes and quiescent hscs. Mitochodrial permeability transition (MPT) preceded the cleavage of caspase-3 and -9 following UA treatment. UA also decreased phosphorylation levels of Akt, and diminished nuclear localization of nfκb in these cells. In rats pretreated with TAA for 6 weeks, a single injection of UA induced remarkable increases in TUNEL- and αsma-dual-positive cells in 24 hr, and significant regression of hepatic fibrosis within 48 hr. Moreover, UA ameliorated hepatic fibrogenesis caused by both chronic TAA administration and BDL. Conclusions: UA ameliorated experimental hepatic fibrosis most likely through specific induction of apoptosis in activated hscs. It is therefore postulated that UA is a potential therapeutic reagent for resolution of hepatic fibrosis. |
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Authors:
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Xu Wang; Kenichi Ikejima; Kazuyoshi Kon; Kumiko Arai; Tomonori Aoyama; Kyoko Okumura; Wataru Abe; Nobuhiro Sato; Sumio Watanabe |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-12-16 |
Journal Detail:
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Title: Journal of hepatology Volume: - ISSN: 0168-8278 ISO Abbreviation: - Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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