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

Molecules

Hyeon-Uk Jeong²  Tae Yeon Kong²  Soon Sang Kwon²  Sung-Woon Hong¹  Sung Hum Yeon¹  Jun-Ho Choi¹  Jae Young Lee¹  Yong Yeon Cho² 

[1] Huons Co., Ltd., Ansan 426-791, Korea; E-Mails:;College of Pharmacy, the Catholic University of Korea, Bucheon 420-743, Korea; E-Mails:

关键词: honokiol;    cytochrome P450 inhibition;    UDP-glucuronosyltransferase inhibition;    human liver microsomes;    drug-drug interaction;   

DOI  :  10.3390/molecules180910681

来源: mdpi

【 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, CYP2C19-mediated [S]-mephenytoin 4-hydroxylation, and UGT1A9-mediated propofol glucuronidation with K_i values of 1.2, 4.9, 0.54, 0.57, and 0.3 μM, respectively. Honokiol also moderately inhibited CYP2B6-mediated bupropion hydroxylation and CYP2D6-mediated bufuralol 1'-hydroxylation with K_i values of 17.5 and 12.0 μM, 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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.