Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction

Rapid Commun Mass Spectrom. 2004;18(19):2273-81. doi: 10.1002/rcm.1621.

Abstract

Here we describe a liquid chromatography/mass spectrometry (LC/MS) method with automated online extraction (LC/LC/MS) to simultaneously determine the in vitro inhibitory potency of herbal extracts on six major human drug-metabolising cytochrome P450 enzymes. Substrates were incubated with a commercially available mixture of CYP1A2/2C8/2C9/2C19/2D6 and 3A4 from baculovirus-infected insect cells and the resulting metabolites were quantified with LC/LC/MS using electrospray ionisation in the selected ion monitoring mode. Consistent inhibitory activities were obtained for known inhibitors and plant extracts using the enzyme/substrate cocktail and the individual enzymes/substrates. Popular herbal remedies including devil's claw root (Harpagophytum procumbens), feverfew herb (Tanacetum parthenium), fo-ti root (Polygonum multiflorum), kava-kava root (Piper methysticum), peppermint oil (Mentha piperita), eucalyptus oil (Eucalyptus globulus), red clover blossom (Trifolium pratense) and grapefruit juice (GJ; Citrus paradisi) could be identified as inhibitors of the applied CYP enzymes with IC(50) values between 20 and 1000 microg/mL.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Chemical Fractionation / methods
  • Chromatography, Liquid / methods*
  • Complex Mixtures / analysis
  • Complex Mixtures / chemistry
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / chemistry*
  • Drug Evaluation, Preclinical / methods
  • Drugs, Chinese Herbal / chemistry
  • Enzyme Activation
  • Enzyme Inhibitors / chemistry
  • Mass Spectrometry / methods*
  • Microchemistry / methods
  • Online Systems*
  • Plant Extracts / chemistry*
  • Plants, Medicinal / chemistry*
  • Protein Interaction Mapping / methods*
  • Reproducibility of Results
  • Robotics / methods
  • Sensitivity and Specificity
  • Substrate Specificity

Substances

  • Complex Mixtures
  • Cytochrome P-450 Enzyme Inhibitors
  • Drugs, Chinese Herbal
  • Enzyme Inhibitors
  • Plant Extracts
  • Cytochrome P-450 Enzyme System