Effects of mace and nutmeg on human cytochrome P450 3A4 and 2C9 activity

Yuka Kimura, Hideyuki Ito, Tsutomu Hatano

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28 Citations (Scopus)

Abstract

Pharmacokinetic or pharmacodynamic interactions between herbal medicines or food constituents and drugs have been studied as crucial factors determining therapeutic efficacy and outcome. Most of these interactions are attributed to inhibition or induction of activity of cytochrome P450 (CYP) metabolic enzymes. Inhibition or induction of CYP enzymes by beverages, including grapefruit, pomegranate, or cranberry juice, has been well documented. Because spices are a common daily dietary component, other studies have reported inhibition of CYP activity by spices or their constituents/derivatives. However, a systematic evaluation of various spices has not been performed. In this study, we investigated effects of 55 spices on CYP3A4 and CYP2C9 activity. Cinnamon, black or white pepper, ginger, mace, and nutmeg significantly inhibited CYP3A4 or CYP2C9 activity. Furthermore, bioassay-guided fractionation of mace (Myristica fragrans) led to isolation and structural characterization of a new furan derivative (1) along with other 16 known compounds, including an acylphenol, neolignans, and phenylpropanoids. Among these isolates, (1S,2R)-1-acetoxy-2-(4- allyl-2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)propane (9) exhibited the most potent CYP2C9 inhibitory activity with an IC50 value comparable to that of sulfaphenazole, a CYP2C9 inhibitor. Compound 9 competitively inhibited CYP2C9-mediated 4'- hydroxylation of diclofenac. The inhibitory constant (Ki) of 9 was determined to be 0.037μM. Compound 9 was found to be 14-fold more potent than was sulfaphenazole.

Original languageEnglish
Pages (from-to)1977-1982
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume33
Issue number12
DOIs
Publication statusPublished - 2010

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Keywords

  • Cytochrome P450
  • Drug interaction
  • Lignan
  • Spice

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

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