Structure-related cytotoxicity and anti-hepatofibric effect of asiatic acid derivatives in rat hepatic stellate cell-line, HSC-T6
| Autor: | Namkyu Lee, Young In Park, Hyun Jung Kim, Eung-Seok Lee, Eun Joo Lee, Yong-Baik Cho, Wie Jong Kwak, Jung Bum Yi, Seung-Hyun Jung, Jeong-Ran Kim, Mi-Sook Dong, Long-Xuan Zhao |
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| Rok vydání: | 2004 |
| Předmět: |
chemistry.chemical_classification
Dose-Response Relationship Drug Cell Survival Chemistry Stereochemistry Carboxylic acid Organic Chemistry Triterpenes Cell Line Rats Structure-Activity Relationship Hydroxyproline chemistry.chemical_compound ASIATIC ACID Drug Discovery β subunit Functional group Hepatocytes Hepatic stellate cell Animals Molecular Medicine Pentacyclic Triterpenes Cytotoxicity IC50 Cell Line Transformed |
| Zdroj: | Archives of Pharmacal Research. 27:512-517 |
| ISSN: | 1976-3786 0253-6269 |
| DOI: | 10.1007/bf02980124 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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