Document Detail


Eupatilin attenuates bile acid-induced hepatocyte apoptosis.
MedLine Citation:
PMID:  16988766     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In cases of cholestasis, bile acids induce hepatocyte apoptosis by activating death receptor-mediated apoptotic signaling cascades. Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredient found in Artemisia asiatica and exhibits cytoprotective effects against experimentally induced gastrointestinal, pancreatic, and hepatic damage. This study was undertaken to examine if eupatilin modulates bile acid-induced hepatocyte apoptosis. METHODS: Huh-BAT cells, a human hepatocellular carcinoma cell line stably transfected with a bile acid transporter, were used in this study. Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining, and its signaling cascades were explored by immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by using selective inhibitors. Eupatilin's in vivo effect on bile acid-induced hepatocyte apoptosis was explored in bile duct-ligated rats. RESULTS: Eupatilin significantly reduced bile acid-mediated hepatocyte apoptosis by attenuating bile acid-induced caspase 8 cleavage. Eupatilin diminished the bile acid-induced activation of mitogen-activated protein kinases, including p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In particular, the eupatilin-mediated inhibition of bile acid-induced c-Jun N-terminal kinase activation was found to be responsible for attenuating caspase 8 cleavage. Moreover, eupatilin diminished hepatocyte apoptosis in bile duct-ligated rats. CONCLUSIONS: Eupatilin attenuates bile acid-induced hepatocyte apoptosis by suppressing bile acid-induced kinase activation. Therefore, eupatilin might be therapeutically efficacious in a variety of human liver diseases associated with cholestasis.
Authors:
Su Cheol Park; Jung-Hwan Yoon; Won Kim; Geum-Youn Gwak; Kang Mo Kim; Sung-Hee Lee; Soo-Mi Lee; Hyo-Suk Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of gastroenterology     Volume:  41     ISSN:  0944-1174     ISO Abbreviation:  J. Gastroenterol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-09-21     Completed Date:  2006-12-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9430794     Medline TA:  J Gastroenterol     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  772-8     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong Chongno-gu, Seoul 110-744, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Caspase 8 / metabolism
Cell Line, Tumor
Cholestasis / drug therapy
Deoxycholic Acid / pharmacology
Flavonoids / pharmacology*
Hepatocytes / drug effects*
Humans
Immunoblotting
In Situ Nick-End Labeling
JNK Mitogen-Activated Protein Kinases / metabolism
MAP Kinase Signaling System / drug effects*
Male
Microscopy, Fluorescence
Models, Animal
Rats
Rats, Sprague-Dawley
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Flavonoids; 22368-21-4/eupatilin; 83-44-3/Deoxycholic Acid; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspase 8
Comments/Corrections
Comment In:
J Gastroenterol. 2006 Aug;41(8):818-9   [PMID:  16988777 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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