Effect of Honokiol on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

被引：48

作者：

Jeong, Hyeon-Uk ^{[1
]}

Kong, Tae Yeon ^{[1
]}

Kwon, Soon Sang ^{[1
]}

Hong, Sung-Woon ^{[2
]}

Yeon, Sung Hum ^{[2
]}

Choi, Jun-Ho ^{[2
]}

Lee, Jae Young ^{[2
]}

Cho, Yong Yeon ^{[1
]}

Lee, Hye Suk ^{[1
]}

机构：

[1] Catholic Univ Korea, Coll Pharm, Puchon 420743, South Korea

[2] Huons Co Ltd, Ansan 426791, South Korea

来源：

MOLECULES | 2013年 / 18卷 / 09期

关键词：

honokiol; cytochrome P450 inhibition; UDP-glucuronosyltransferase inhibition; human liver microsomes; drug-drug interaction; DRUG-DRUG INTERACTIONS; IN-VITRO METABOLISM; MAGNOLIA-OFFICINALIS; ANTICANCER AGENTS; GRAPEFRUIT JUICE; HERBAL MEDICINES; INHIBITION; GLUCURONIDATION; BERGAMOTTIN; PATHWAY;

D O I：

10.3390/molecules180910681

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Honokiol is a bioactive component isolated from the medicinal herbs Magnolia officinalis and Magnolia grandiflora that has antioxidative, anti-inflammatory, antithrombotic, and antitumor activities. The inhibitory potentials of honokiol on eight major human cytochrome P450 (CYP) enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4, and four UDP-glucuronosyltransferases (UGTs) 1A1, 1A4, 1A9, and 2B7 in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. Honokiol strongly inhibited CYP1A2-mediated phenacetin O-deethylation, CYP2C8-mediated amodiaquine N-deethylation, CYP2C9-mediated diclofenac 4-hydroxylation, CYP2C19mediated [S]-mephenytoin 4-hydroxylation, and UGT1A9-mediated propofol glucuronidation with Ki values of 1.2, 4.9, 0.54, 0.57, and 0.3 mu M, respectively. Honokiol also moderately inhibited CYP2B6-mediated bupropion hydroxylation and CYP2D6-mediated bufuralol 1'-hydroxylation with Ki values of 17.5 and 12.0 mu M, respectively. These in vitro results indicate that honokiol has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, CYP2C8, CYP2C9, CYP2C19, and UGT1A9.

引用

页码：10681 / 10693

页数：13

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