1. Effect of honokiol on cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes.
- Author
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Jeong HU, Kong TY, Kwon SS, Hong SW, Yeon SH, Choi JH, Lee JY, Cho YY, and Lee HS
- Subjects
- Aryl Hydrocarbon Hydroxylases metabolism, Bupropion metabolism, Drugs, Chinese Herbal pharmacology, Ethanolamines metabolism, Glucuronosyltransferase metabolism, Herb-Drug Interactions, Humans, Hydroxylation, Inactivation, Metabolic, Inhibitory Concentration 50, Liver enzymology, Microsomes, Liver drug effects, Phenacetin metabolism, Aryl Hydrocarbon Hydroxylases antagonists & inhibitors, Biphenyl Compounds pharmacology, Enzyme Inhibitors pharmacology, Glucuronosyltransferase antagonists & inhibitors, Lignans pharmacology, Microsomes, Liver enzymology
- Abstract
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. more...
- Published
- 2013
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