Effect of honokiol on cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes

Hyeon Uk Jeong; Tae Yeon Kong; Soon Sang Kwon; Sung Woon Hong; Sung Hum Yeon; Jun Ho Choi; Jae Young Lee; Yong Yeon Cho; Hye Suk Lee

doi:10.3390/molecules180910681

Effect of honokiol on cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes

Hyeon Uk Jeong
, Tae Yeon Kong
, Soon Sang Kwon
, Sung Woon Hong
, Sung Hum Yeon
, Jun Ho Choi
, Jae Young Lee
, Yong Yeon Cho
, Hye Suk Lee

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

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 Kⁱ 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.

Original language	English
Pages (from-to)	10681-10693
Number of pages	13
Journal	Molecules
Volume	18
Issue number	9
DOIs	https://doi.org/10.3390/molecules180910681
State	Published - Sep 2013

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cytochrome P450 inhibition
Drug-drug interaction
Honokiol
Human liver microsomes
UDP-glucuronosyltransferase inhibition

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10.3390/molecules180910681

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@article{a7830225f18d414280e2cf593a9ba6fe,

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 Ki 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 Ki 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.",

keywords = "Cytochrome P450 inhibition, Drug-drug interaction, Honokiol, Human liver microsomes, UDP-glucuronosyltransferase inhibition",

author = "Jeong, \{Hyeon Uk\} and Kong, \{Tae Yeon\} and Kwon, \{Soon Sang\} and Hong, \{Sung Woon\} and Yeon, \{Sung Hum\} and Choi, \{Jun Ho\} and Lee, \{Jae Young\} and Cho, \{Yong Yeon\} and Lee, \{Hye Suk\}",

year = "2013",

month = sep,

doi = "10.3390/molecules180910681",

language = "English",

volume = "18",

pages = "10681--10693",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

TY - JOUR

T1 - Effect of honokiol on cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes

AU - Jeong, Hyeon Uk

AU - Kong, Tae Yeon

AU - Kwon, Soon Sang

AU - Hong, Sung Woon

AU - Yeon, Sung Hum

AU - Choi, Jun Ho

AU - Lee, Jae Young

AU - Cho, Yong Yeon

AU - Lee, Hye Suk

PY - 2013/9

Y1 - 2013/9

N2 - 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 Ki 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 Ki 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.

AB - 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 Ki 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 Ki 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.

KW - Cytochrome P450 inhibition

KW - Drug-drug interaction

KW - Honokiol

KW - Human liver microsomes

KW - UDP-glucuronosyltransferase inhibition

UR - https://www.scopus.com/pages/publications/84885153952

U2 - 10.3390/molecules180910681

DO - 10.3390/molecules180910681

M3 - Article

C2 - 24005963

AN - SCOPUS:84885153952

SN - 1420-3049

VL - 18

SP - 10681

EP - 10693

JO - Molecules

JF - Molecules

IS - 9

ER -

Effect of honokiol on cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes

Abstract

UN SDGs

Keywords

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