Effects of Mace and Nutmeg on Human Cytochrome P450 3A4 and 2C9 Activity
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概要
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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 0.037 μM. Compound 9 was found to be 14-fold more potent than was sulfaphenazole.
著者
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波多野 力
Department Of Pharmacognosy Graduate School Of Medicine Dentistry And Pharmaceutical Sciences Okayam
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Ito Hideyuki
Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry, and Pharmaceutical Scie
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Hatano Tsutomu
エジプト
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Hatano Tsutomu
Division Of Pharmaceutical Sciences Okayama University Graduate School Of Medicine Dentistry And Pha
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KIMURA Yuka
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and P
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Ito Hideyuki
Department Of Pharmacognosy Okayama University Graduate School Of Medicine Dentistry And Pharmaceuti
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Hatano Tsutomu
Department Of Pharmacognosy Okayama University Graduate School Of Medicine Dentistry And Pharmaceuti
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Ito Hideyuki
Division Of Pharmaceutical Sciences Graduate School Of Medicine Dentistry And Pharmaceutical Science
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Hatano Tsutomu
Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Kimura Yuka
Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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