title: Effect of honokiol on cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes.
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.
authors.affiliation: College of Pharmacy, the Catholic University of Korea, Bucheon 420-743, Korea.
authors.forename: Hyeon-Uk
authors.initials: HU
authors.lastname: Jeong
authors.forename: Tae Yeon
authors.initials: TY
authors.lastname: Kong
authors.forename: Soon Sang
authors.initials: SS
authors.lastname: Kwon
authors.forename: Sung-Woon
authors.initials: SW
authors.lastname: Hong
authors.forename: Sung Hum
authors.initials: SH
authors.lastname: Yeon
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D016642:Bupropion / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004983:Ethanolamines / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D006900:Hydroxylation; D008658:Inactivation, Metabolic; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010615:Phenacetin / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D001713:Biphenyl Compounds; D016642:Bupropion; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D014453:Glucuronosyltransferase; D017705:Lignans; D010615:Phenacetin; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C010831:bufuralol