Structure-related cytotoxicity and anti-hepatofibric effect of asiatic acid derivatives in rat hepatic stellate cell-line, HSC-T6

被引:34
作者
Dong, MS [1 ]
Jung, SH
Kim, HJ
Kim, JR
Zhao, LX
Lee, ES
Lee, EJ
Yi, JB
Lee, N
Cho, YB
Kwak, WJ
Park, YI
机构
[1] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea
[2] Yeungnam Univ, Coll Pharm, Kyongsan 712749, South Korea
[3] SK Chem, Life Sci Res Ctr, Suwon 440745, South Korea
关键词
asiatic acid derivatives; rat hepatic stellate cell; cytotoxicity; anti-hepatofibrotic effect;
D O I
10.1007/BF02980124
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 muM to over 2000 muM of IC50 depending on AA functional group modifications. Substituting the hydroxyl group at the C(2) to NdropC 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.
引用
收藏
页码:512 / 517
页数:6
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