Corydaline inhibits multiple cytochrome P450 and UDP- glucuronosyltransferase enzyme activities in human liver microsomes

Hye Young Ji; Kwang Hyeon Liu; Hyeri Lee; Sae Rom Im; Hyun Joo Shim; Miwon Son; Hye Suk Lee

doi:10.3390/molecules16086591

Corydaline inhibits multiple cytochrome P450 and UDP- glucuronosyltransferase enzyme activities in human liver microsomes

Hye Young Ji, Kwang Hyeon Liu, Hyeri Lee, Sae Rom Im, Hyun Joo Shim, Miwon Son, Hye Suk Lee

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

30 Scopus citations

Abstract

Corydaline is a bioactive alkaloid with various antiacetylcholinesterase, antiallergic, and antinociceptive activities found in the medicinal herb Corydalis Tubers. The inhibitory potential of corydaline on the activities of seven major human cytochrome P450 and four UDP-glucuronosyltransferase enzymes in human liver microsomes was investigated using LC-tandem MS. Corydaline was found to inhibit CYP2C19-catalyzed S-mephenytoin-4'-hydroxylatoin and CYP2C9-catalyzed diclofenac 4-hydroxylation, with Ki values of 1.7 and 7.0 μM, respectively. Corydaline also demonstrated moderate inhibition of UGT1A1-mediated 17β-estradiol 3-glucuronidation and UGT1A9-mediated propofol glucuronidation with K _i values of 57.6 and 37.3 μM, respectively. In the presence of corydaline, CYP3A-mediated midazolam hydroxylation showed a decrease with increasing preincubation time in a dose-dependent manner with Ki values of 30.0 μM. These in vitro results suggest that corydaline should be evaluated for potential pharmacokinetic drug interactions in vivo due to potent inhibition of CYP2C19 and CYP2C9.

Original language	English
Pages (from-to)	6591-6602
Number of pages	12
Journal	Molecules
Volume	16
Issue number	8
DOIs	https://doi.org/10.3390/molecules16086591
State	Published - Aug 2011

Keywords

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

UN SDGs

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

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10.3390/molecules16086591

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title = "Corydaline inhibits multiple cytochrome P450 and UDP- glucuronosyltransferase enzyme activities in human liver microsomes",

abstract = "Corydaline is a bioactive alkaloid with various antiacetylcholinesterase, antiallergic, and antinociceptive activities found in the medicinal herb Corydalis Tubers. The inhibitory potential of corydaline on the activities of seven major human cytochrome P450 and four UDP-glucuronosyltransferase enzymes in human liver microsomes was investigated using LC-tandem MS. Corydaline was found to inhibit CYP2C19-catalyzed S-mephenytoin-4'-hydroxylatoin and CYP2C9-catalyzed diclofenac 4-hydroxylation, with Ki values of 1.7 and 7.0 μM, respectively. Corydaline also demonstrated moderate inhibition of UGT1A1-mediated 17β-estradiol 3-glucuronidation and UGT1A9-mediated propofol glucuronidation with K i values of 57.6 and 37.3 μM, respectively. In the presence of corydaline, CYP3A-mediated midazolam hydroxylation showed a decrease with increasing preincubation time in a dose-dependent manner with Ki values of 30.0 μM. These in vitro results suggest that corydaline should be evaluated for potential pharmacokinetic drug interactions in vivo due to potent inhibition of CYP2C19 and CYP2C9.",

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

author = "Ji, {Hye Young} and Liu, {Kwang Hyeon} and Hyeri Lee and Im, {Sae Rom} and Shim, {Hyun Joo} and Miwon Son and Lee, {Hye Suk}",

year = "2011",

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T1 - Corydaline inhibits multiple cytochrome P450 and UDP- glucuronosyltransferase enzyme activities in human liver microsomes

AU - Ji, Hye Young

AU - Liu, Kwang Hyeon

AU - Lee, Hyeri

AU - Im, Sae Rom

AU - Shim, Hyun Joo

AU - Son, Miwon

AU - Lee, Hye Suk

PY - 2011/8

Y1 - 2011/8

N2 - Corydaline is a bioactive alkaloid with various antiacetylcholinesterase, antiallergic, and antinociceptive activities found in the medicinal herb Corydalis Tubers. The inhibitory potential of corydaline on the activities of seven major human cytochrome P450 and four UDP-glucuronosyltransferase enzymes in human liver microsomes was investigated using LC-tandem MS. Corydaline was found to inhibit CYP2C19-catalyzed S-mephenytoin-4'-hydroxylatoin and CYP2C9-catalyzed diclofenac 4-hydroxylation, with Ki values of 1.7 and 7.0 μM, respectively. Corydaline also demonstrated moderate inhibition of UGT1A1-mediated 17β-estradiol 3-glucuronidation and UGT1A9-mediated propofol glucuronidation with K i values of 57.6 and 37.3 μM, respectively. In the presence of corydaline, CYP3A-mediated midazolam hydroxylation showed a decrease with increasing preincubation time in a dose-dependent manner with Ki values of 30.0 μM. These in vitro results suggest that corydaline should be evaluated for potential pharmacokinetic drug interactions in vivo due to potent inhibition of CYP2C19 and CYP2C9.

AB - Corydaline is a bioactive alkaloid with various antiacetylcholinesterase, antiallergic, and antinociceptive activities found in the medicinal herb Corydalis Tubers. The inhibitory potential of corydaline on the activities of seven major human cytochrome P450 and four UDP-glucuronosyltransferase enzymes in human liver microsomes was investigated using LC-tandem MS. Corydaline was found to inhibit CYP2C19-catalyzed S-mephenytoin-4'-hydroxylatoin and CYP2C9-catalyzed diclofenac 4-hydroxylation, with Ki values of 1.7 and 7.0 μM, respectively. Corydaline also demonstrated moderate inhibition of UGT1A1-mediated 17β-estradiol 3-glucuronidation and UGT1A9-mediated propofol glucuronidation with K i values of 57.6 and 37.3 μM, respectively. In the presence of corydaline, CYP3A-mediated midazolam hydroxylation showed a decrease with increasing preincubation time in a dose-dependent manner with Ki values of 30.0 μM. These in vitro results suggest that corydaline should be evaluated for potential pharmacokinetic drug interactions in vivo due to potent inhibition of CYP2C19 and CYP2C9.

KW - Corydaline

KW - Cytochrome P450 inhibition

KW - Drug-drug interaction

KW - Human liver microsomes

KW - UDP-glucuronosyltransferase inhibition

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Corydaline inhibits multiple cytochrome P450 and UDP- glucuronosyltransferase enzyme activities in human liver microsomes

Abstract

Keywords

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