High-dose green tea polyphenol intake decreases CYP3A expression in a liver-specific manner with increases in blood substrate drug concentrations

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• 作者：Nobutomo Ikarashi¹ ; Sosuke Ogawa¹ ; Ryuta Hirobe ; Yoshiki Kusunoki ; Risako Kon ; Wataru Ochiai ; Kiyoshi Sugiyama ; ^{sugiyama@hoshi.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cytochrome P450 ; Green tea polyphenol ; Liver ; Small intestine
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：30 June 2016
• 年：2016
• 卷：89
• 期：Complete
• 页码：137-145
• 全文大小：1062 K

文摘

In recent years, the intake of functional foods containing high-doses of green tea polyphenols (GP) has been increasing. In this study, the long-term safety of high-dose GP was assessed from a pharmacokinetic point of view by focusing on the drug-metabolizing enzyme, cytochrome P450 (CYP). Mice were fed a diet containing 3% GP for 4 weeks, and the CYP expression levels and activity were determined. The GP-treated group showed a significant decrease in the hepatic CYP3A and an increase in the hepatic CYP2C expression compared with the control group. CYP1A, CYP2D, and CYP2E expression were not different between the GP-treated and the control groups. In the small intestine, there were no differences in the CYP3A protein levels between the groups. The increase in the plasma triazolam concentration in the GP-treated group was observed. Although no changes were found in the hepatic CYP3A levels in mice receiving a diet containing 0.1% GP for 4 weeks, a significant decrease was seen in the hepatic CYP3A level in mice receiving a diet containing 3% GP for only 1 week. This study revealed that the intake of a high-dose GP results in a liver-specific decrease in the CYP3A expression level. The results also indicated that the effects of GP on CYP3A were not observed following the intake of a low-dose GP. In the future, caution should be taken in cases when functional foods containing a high-dose GP are concomitantly consumed with a CYP3A substrate drug.