Comprehensive investigation of stereoselective food drug interaction potential of resveratrol on nine p450 and six ugt isoforms in human liver microsomes

Seung Bae Ji; So Young Park; Subin Bae; Hyung Ju Seo; Sin Eun Kim; Gyung Min Lee; Zhexue Wu; Kwang Hyeon Liu

doi:10.3390/pharmaceutics13091419

Comprehensive investigation of stereoselective food drug interaction potential of resveratrol on nine p450 and six ugt isoforms in human liver microsomes

Seung Bae Ji, So Young Park, Subin Bae, Hyung Ju Seo, Sin Eun Kim, Gyung Min Lee, Zhexue Wu, Kwang Hyeon Liu

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

7 Scopus citations

Abstract

The stereoselectivity of the food drug inhibition potential of resveratrol on cytochrome P450s and uridine 5′-diphosphoglucuronosyl transferases was investigated in human liver micro-somes. Resveratrol enantiomers showed stereoselective inhibition of CYP2C9, CYP3A, and UGT1A1. The inhibitions of CYP1A2, CYP2B6, and CYP2C19 by resveratrol were stereo-nonselective. The estimated Ki values determined for CYP1A2 were 13.8 and 9.2 μM for trans-and cisresveratrol, respectively. Trans-resveratrol noncompetitively inhibited CYP3A and UGT1A1 activities with Ki values of 23.8 and 27.4 μM, respectively. Trans-resveratrol inhibited CYP1A2, CYP2C19, CYP2E1, and CYP3A in a time-dependent manner with Ki shift values >2.0, while cis-resveratrol time-dependently inhibited CYP2C19 and CYP2E1. The time-dependent inhibition of trans-resveratrol against CYP3A4, CYP2E1, CYP2C19, and CYP1A2 was elucidated using glutathione as a trapping reagent. This information helped the prediction of food drug interaction potentials between resveratrol and co-administered drugs which are mainly metabolized by UGT1A1, CYP1A2, CYP2C19, CYP2E1, and CYP3A.

Original language	English
Article number	1419
Journal	Pharmaceutics
Volume	13
Issue number	9
DOIs	https://doi.org/10.3390/pharmaceutics13091419
State	Published - Sep 2021

Keywords

Cytochrome P450
Food drug interactions
Resveratrol
Stereoselectivity
Uridine 5′-diphosphoglucuronosyl transferase

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10.3390/pharmaceutics13091419

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title = "Comprehensive investigation of stereoselective food drug interaction potential of resveratrol on nine p450 and six ugt isoforms in human liver microsomes",

abstract = "The stereoselectivity of the food drug inhibition potential of resveratrol on cytochrome P450s and uridine 5′-diphosphoglucuronosyl transferases was investigated in human liver micro-somes. Resveratrol enantiomers showed stereoselective inhibition of CYP2C9, CYP3A, and UGT1A1. The inhibitions of CYP1A2, CYP2B6, and CYP2C19 by resveratrol were stereo-nonselective. The estimated Ki values determined for CYP1A2 were 13.8 and 9.2 μM for trans-and cisresveratrol, respectively. Trans-resveratrol noncompetitively inhibited CYP3A and UGT1A1 activities with Ki values of 23.8 and 27.4 μM, respectively. Trans-resveratrol inhibited CYP1A2, CYP2C19, CYP2E1, and CYP3A in a time-dependent manner with Ki shift values >2.0, while cis-resveratrol time-dependently inhibited CYP2C19 and CYP2E1. The time-dependent inhibition of trans-resveratrol against CYP3A4, CYP2E1, CYP2C19, and CYP1A2 was elucidated using glutathione as a trapping reagent. This information helped the prediction of food drug interaction potentials between resveratrol and co-administered drugs which are mainly metabolized by UGT1A1, CYP1A2, CYP2C19, CYP2E1, and CYP3A.",

keywords = "Cytochrome P450, Food drug interactions, Resveratrol, Stereoselectivity, Uridine 5′-diphosphoglucuronosyl transferase",

author = "Ji, {Seung Bae} and Park, {So Young} and Subin Bae and Seo, {Hyung Ju} and Kim, {Sin Eun} and Lee, {Gyung Min} and Zhexue Wu and Liu, {Kwang Hyeon}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = sep,

doi = "10.3390/pharmaceutics13091419",

language = "English",

volume = "13",

journal = "Pharmaceutics",

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T1 - Comprehensive investigation of stereoselective food drug interaction potential of resveratrol on nine p450 and six ugt isoforms in human liver microsomes

AU - Ji, Seung Bae

AU - Park, So Young

AU - Bae, Subin

AU - Seo, Hyung Ju

AU - Kim, Sin Eun

AU - Lee, Gyung Min

AU - Wu, Zhexue

AU - Liu, Kwang Hyeon

PY - 2021/9

Y1 - 2021/9

N2 - The stereoselectivity of the food drug inhibition potential of resveratrol on cytochrome P450s and uridine 5′-diphosphoglucuronosyl transferases was investigated in human liver micro-somes. Resveratrol enantiomers showed stereoselective inhibition of CYP2C9, CYP3A, and UGT1A1. The inhibitions of CYP1A2, CYP2B6, and CYP2C19 by resveratrol were stereo-nonselective. The estimated Ki values determined for CYP1A2 were 13.8 and 9.2 μM for trans-and cisresveratrol, respectively. Trans-resveratrol noncompetitively inhibited CYP3A and UGT1A1 activities with Ki values of 23.8 and 27.4 μM, respectively. Trans-resveratrol inhibited CYP1A2, CYP2C19, CYP2E1, and CYP3A in a time-dependent manner with Ki shift values >2.0, while cis-resveratrol time-dependently inhibited CYP2C19 and CYP2E1. The time-dependent inhibition of trans-resveratrol against CYP3A4, CYP2E1, CYP2C19, and CYP1A2 was elucidated using glutathione as a trapping reagent. This information helped the prediction of food drug interaction potentials between resveratrol and co-administered drugs which are mainly metabolized by UGT1A1, CYP1A2, CYP2C19, CYP2E1, and CYP3A.

AB - The stereoselectivity of the food drug inhibition potential of resveratrol on cytochrome P450s and uridine 5′-diphosphoglucuronosyl transferases was investigated in human liver micro-somes. Resveratrol enantiomers showed stereoselective inhibition of CYP2C9, CYP3A, and UGT1A1. The inhibitions of CYP1A2, CYP2B6, and CYP2C19 by resveratrol were stereo-nonselective. The estimated Ki values determined for CYP1A2 were 13.8 and 9.2 μM for trans-and cisresveratrol, respectively. Trans-resveratrol noncompetitively inhibited CYP3A and UGT1A1 activities with Ki values of 23.8 and 27.4 μM, respectively. Trans-resveratrol inhibited CYP1A2, CYP2C19, CYP2E1, and CYP3A in a time-dependent manner with Ki shift values >2.0, while cis-resveratrol time-dependently inhibited CYP2C19 and CYP2E1. The time-dependent inhibition of trans-resveratrol against CYP3A4, CYP2E1, CYP2C19, and CYP1A2 was elucidated using glutathione as a trapping reagent. This information helped the prediction of food drug interaction potentials between resveratrol and co-administered drugs which are mainly metabolized by UGT1A1, CYP1A2, CYP2C19, CYP2E1, and CYP3A.

KW - Cytochrome P450

KW - Food drug interactions

KW - Resveratrol

KW - Stereoselectivity

KW - Uridine 5′-diphosphoglucuronosyl transferase

UR - http://www.scopus.com/inward/record.url?scp=85114767320&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics13091419

DO - 10.3390/pharmaceutics13091419

M3 - Article

AN - SCOPUS:85114767320

SN - 1999-4923

VL - 13

JO - Pharmaceutics

JF - Pharmaceutics

IS - 9

M1 - 1419

ER -

Comprehensive investigation of stereoselective food drug interaction potential of resveratrol on nine p450 and six ugt isoforms in human liver microsomes

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