Inhibitory Effects of Eight Green Tea Catechins on Cytochrome P450 1A2, 2C9, 2D6, and 3A4 Activities

Abstract

-PURPOSE:Green tea is a traditional beverage that has been enjoyed by the Japanese to this day. Recently, there has been an increase in the consumption of green tea beverage having high concentrations of catechins, such as (-)-epigallocatechin-3-O-gallate (EGCG). Many people tend to ingest large amounts of catechins through the frequent consumption of green tea beverage, and this dietary habit may lead to unwanted interactions between the catechins in green tea and medicinal drug. METHODS: The inhibitory effects of eight green tea catechins on drug metabolizing enzymes, cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4, were investigated in human liver microsomes. Incubation was initiated by the addition of cocktail probe drugs that served as specific substrates for each CYP, and the resulting metabolites were analyzed by LC-MS. RESULTS: From a comparison of the fifty percent inhibitory concentration (IC50) values of the eight green tea catechins, it was found that non-gallated catechins did not inhibit CYPs, whereas gallated catechins inhibited all CYPs except CYP2D6. Among them, CYP2C9 was most strongly inhibited by (-)-catechin-3-Ogallate (CG) (7.60 µM), and CYP1A2 was most strongly inhibited by EGCG (8.93 µM). Catechin gallate exhibited non-competitive inhibition of CYP2C9, and its Ki value was 9.76 ± 0.47µM. The present study is the first to report the inhibitory effect of CG on CYP2C9. In contrast, EGCG showed competitive inhibition of CYP1A2, and its Ki value was 14.3 ± 0.09 µM. CONCLUSION: Previous reports had predicted that plasma EGCG concentration reached 7.4 µM after ingesting green tea having high concentrations of catechins. That concentration of EGCG is equivalent to one-half to one-third of its Ki value for CYP1A2 and CYP3A4 in this study. The ingestion of beverages containing large amounts of green tea catechins together with drugs that are metabolized by CYP1A2, CYP2C9, and CYP3A4 should be avoided.

Development and validation of a sensitive and specific LC–MS/MS cocktail assay for CYP450 enzymes: Application to study the effect of catechin on rat hepatic CYP activity

“…Protein precipitation is less time consuming and requires a minimal method development (Alshammari, Al‐Hassan, Hadda, & Aljofan, ) The method also has a short incubation time of 15 min and an analysis time of 8 min compared to other methods that could take up to 60 min for incubation and 25 min for analysis (Li, Huang, Nikolic, & van Breemen, ) The calibration curves were linear over concentration ranges of 10–500 ng/mL for the metabolites under investigation. This study is the first to investigate the effects of catechin in rat hepatic CYP activity using a cocktail analysis (Chow et al, ; Satoh et al, ).…”

“…Many studies support the cardioprotective effects of catechins through reductions in systemic blood pressure, atherosclerosis, platelet activation, and thrombus formation (Mangels & Mohler, ). One study found that CYP1A2, CYP2C9, and CYP3A4 were inhibited by catechins in green tea, and the authors recommend avoiding the consumption of large quantities of foods containing catechins when taking medications that are metabolized by these CYP enzymes (Satoh, Fujisawa, Nakamura, Takahashi, & Watanabe, ).…”

Health Functions and Related Molecular Mechanisms of Tea Components: An Update Review

“…Considering the health functions as shown in vivo, tea might serve as a functional food and pharmaceutical for the prevention and treatment of T2DM. Satoh et al reported that black tea aqueous extract inhibited the hydrolysis of disaccharides into monosaccharides by the α-glucosidase in the small intestine, thereby blocking the sodium-dependent glucose cotransporter 1 and glucose transporter (GLUT) 2-mediated absorption of the dietary glucose [31]. Li et al declared that TPS treatment could alleviate insulin resistance and decrease blood glucose in diabetic mice, which might be mediated by the regulation of the PI3K/Akt signal pathway as revealed by the up-regulated expression of PI3Kp85/p-Akt/GLUT4-signaling molecules [147].…”

Green tea: Chemical composition, biological effects and health benefits

“…Catechins present in the green tea suppress the liver metabolizing enzymes like CYP 450. Inhibitory action of green tea is to CYP 450 decrease the bioavailability of sildenafil (Misaka et al, 2013;Satoh et al, 2016). Green tea also disturbs pharmacological action and absorption pattern of various drugs like MAO inhibitors, lithium and adenosine.…”