Document Detail


Structure-related cytotoxicity and anti-hepatofibric effect of asiatic acid derivatives in rat hepatic stellate cell-line, HSC-T6.
MedLine Citation:
PMID:  15202556     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The structural relationship of 16 asiatic acid (AA) derivatives, including AA and asiaticoside (AS) to cytotoxicity and anti-hepatofibrotic activity in HSC-T6 cells, were investigated. Cytotoxicities of AA derivatives varied from 5.5 microM to over 2000 microM of IC50 depending on AA functional group modifications. Substituting the hydroxyl group at the C(2) to N[triple bond]C and substituting bulky groups for dihydroxyl groups at (3), (23) of the A-ring increased the cytotoxicity, but keto group at C(11) and benzoyl ester at C(2) were greatly reduced it. Modification of the carboxylic acid group at C28 also reduced the cytotoxicity. The collagen synthesis determined by hydroxyproline content in the cells was inhibited from a maximum of 48% (Zlx-i-85 and 87) to 15% (AS) by AA derivatives. The anti-hepatofibrotic effect of these compounds might be due to the reduced expression of prolyl 4-hydroxylase alpha and beta subunits and TIMP2. However, the inhibition of collagen by asiaticoside derivatives did not show any structural-activity relationship.
Authors:
Mi-Sook Dong; Seung-Hyun Jung; Hyun-jung Kim; Jeong-Ran Kim; Long-Xuan Zhao; Eung-Seok Lee; Eun-Joo Lee; Jung Bum Yi; Namkyu Lee; Yong-Baik Cho; Wie Jong Kwak; Young In Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of pharmacal research     Volume:  27     ISSN:  0253-6269     ISO Abbreviation:  Arch. Pharm. Res.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-06-18     Completed Date:  2005-01-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8000036     Medline TA:  Arch Pharm Res     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  512-7     Citation Subset:  IM    
Affiliation:
School of Life sciences and Biotechnology, Korea University, Seoul 136-701, Korea. msdong@korea.ac.kr
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Line, Transformed
Cell Survival / drug effects,  physiology
Dose-Response Relationship, Drug
Hepatocytes / drug effects*,  physiology
Rats
Structure-Activity Relationship
Triterpenes / chemistry*,  toxicity*
Chemical
Reg. No./Substance:
0/Triterpenes; 464-92-6/asiatic acid

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


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