Luteolin is a rare substrate of human catechol-O-methyltransferase favoring a para-methylation

被引：23

作者：

Chen, Zhong-Jian ^{[1
,2
]}

Dai, Yan-Qing ^{[1
]}

Kong, Si-Si ^{[1
]}

Song, Fei-Feng ^{[1
]}

Li, Li-Ping ^{[1
]}

Ye, Jian-Feng ^{[3
]}

Wang, Ru-Wei ^{[3
]}

Zeng, Su ^{[1
]}

Zhou, Hui ^{[1
]}

Jiang, Hui-Di ^{[1
]}

机构：

[1] Zhejiang Univ, Dept Pharmaceut Anal & Drug Metab, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Canc Hosp, Zhejiang Canc Res Inst, Hangzhou, Zhejiang, Peoples R China

[3] Conba Pharmaceut Co Ltd, Dept Res & Dev, Hangzhou, Zhejiang, Peoples R China

来源：

MOLECULAR NUTRITION & FOOD RESEARCH | 2013年 / 57卷 / 05期

关键词：

Catechol-O-methyltransferase (COMT); Demethylation; Luteolin; Methylation; Regioselectivity; IN-VITRO; FLAVONOIDS; METABOLISM; VARIANT; COMT;

D O I：

10.1002/mnfr.201200584

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

Scope The study aimed to investigate the regioselectivity of methylation of luteolin (3,4,5,7-tetrahydroxyflavone) in human in vitro and in vivo. Methods and results Recombinant human catechol-O-methyltransferase (COMT) and human liver S9 were utilized to study the kinetics of meta (3)- and para (4)- methylation of luteolin, and urine samples from volunteers after giving a luteolin-containing formulation were collected to determine the ratio of para-/meta-production. The results showed luteolin favored a para-methylation, with a ratio of of para-/meta-production in CLint (1.43 in recombinant human COMT and 1.47 in human liver S9), which was contrary to the known substrates of COMT. However, the result of urine sample assay showed a preference of meta-methylation with a ratio of of para-/meta-production (0.460 +/- 0.126). To elucidate the mechanism for different preference of methylation of luteolin in vitro and in vivo, metabolism stability of the meta- and para-methylated luteolin was evaluated in human liver microsomes and recombinant human CYP450s, which revealed that para-methylated luteolin was more easily demethylated by human CYP1A2 and CYP3A4/5 than meta-methylated luteolin. Conclusion Luteolin was a rare substrate of human COMT favoring a para-methylation, but further demethylation by human CYP1A2 and CYP3A4/5 caused a preference of accumulation in meta-methylated luteolin in vivo.

引用

页码：877 / 885

页数：9

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