Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes

  • Tingting Li
  • Ning Li
  • Qinglong Guo
  • Hui Ji
  • Di Zhao
  • Shan Xie
  • Xiaonan Li
  • Zhixia Qiu
  • Deen Han
  • Xijing Chen
  • Qidong You
Original Paper

Abstract

Wogonin, derived from the root of Scutellaria baicalensis, is a popular herb for its anticancer, anti-inflammatory, neuroprotective and anti-convulsant effects. The purpose of this study was to investigate the effect of wogonin on human hepatic cytochrome P450s (CYP450s) in vitro. Isoform-specific substrate probes of CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 were incubated in human liver microsomes with or without wogonin. IC50 and Ki values were estimated and the types of inhibition were determined. Wogonin was a potent, competitive inhibitor of CYP1A2 (Ki = 0.24 μM), and a weak inhibitor of CYP2C19 (IC50 = 101.10 μM), but was not able to inhibit CYP2C9, CYP2D6, CYP2E1 and CYP3A4 (IC50 > 200 μM). Wogonin could inhibit the activity of CYP1A2 and CYP2C19 with varying potency, while it is a strong inhibitor of CYP1A2. These findings suggested that it was necessary to study the potential pharmacokinetic drug interaction in vivo.

Keywords

Cytochrome P450 Drug–drug interaction Wogonin Enzyme inhibition 

Abbreviations

CYP

Cytochrome P450

HPLC

High performance liquid chromatography

LC–MS

High-performance liquid chromatography–electrospray spectrometry

IS

Internal standard

IC50

50% inhibitory concentration

Ki

Equilibrium dissociation constant for reversible inhibitor

Km

The Michaelis constant

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Copyright information

© Springer-Verlag France 2011

Authors and Affiliations

  • Tingting Li
    • 1
  • Ning Li
    • 1
  • Qinglong Guo
    • 2
  • Hui Ji
    • 1
  • Di Zhao
    • 1
  • Shan Xie
    • 1
  • Xiaonan Li
    • 1
  • Zhixia Qiu
    • 1
  • Deen Han
    • 1
  • Xijing Chen
    • 1
    • 3
  • Qidong You
    • 2
  1. 1.School of PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.Jiangsu Key Laboratory of Carcinogenesis and InterventionChina Pharmaceutical UniversityNangingPeople’s Republic of China
  3. 3.Center of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNangingPeople’s Republic of China

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