Effect of Camellia sinensis extract on the expression level of transcription factors and cytochrome P450 genes coding phase I drug-metabolizing enzymes

ANNA BOGACZ, MONIKA KARASIEWICZ, JOANNA BARTKOWIAK-WIECZOREK, MARCIN OŻAROWSKI, AGNIESZKA SEREMAK-MROZIKIEWICZ, RADOSŁAW KUJAWSKI, PRZEMYSŁAW Ł. MIKOŁAJCZAK, BEATA MROZIKIEWICZ-RAKOWSKA, TERESA BOBKIEWICZ-KOZŁOWSKA, BOGUSŁAW CZERNY, EDMUND GRZEŚKOWIAK, PRZEMYSŁAW M. MROZIKIEWICZ

Abstract

Green tea (Camellia sinensis) is widely used as a popular beverage and dietary supplement that can significantly reduce the risk of many diseases. Despite the widespread use of green tea, the data regarding the safety as well as herb-drug interactions are limited. Therefore, the aim of our study was to assess the influence of standardized green tea extract (GTE) containing 61% catechins and 0.1% caffeine on the expression level of rat CYP genes and the corresponding transcription factors expression by realtime PCR. The findings showed that GTE resulted in a significant decrease of CYP2C6 expression level by 68% (p<0.001). In case of CYP3A1 and CYP3A2, the mRNA levels were also reduced by extract but in a lesser degree compared to CYP2C6. Simultaneously the significant increase in the mRNA level of CAR, RXR and GR factors was observed by 54% (p<0.05), 79% (p<0.001) and 23% (p<0.05), respectively after 10 days of green tea extract administration. In addition, there was noted a small increase of CYP1A1 expression level by 21% (p>0.05) was noted. No statistically significant differences were observed for CYP1A2 and CYP2D1/2. In the same study we observed an increase in amount of ARNT gene transcript by 27% (p<0.05) in the long-term use. However, green tea extract showed the ability to stimulate HNF-1α both after 3 and 10 days of treatment by 30% (p<0.05) and 80% (p<0.001), respectively. In contrast, no change was observed in the concentration of HNF-4α cDNA. These results suggest that GTE may change the expression of CYP enzymes, especially CYP2C6 (homologue to human CYP2C9) and may participate in clinically significant interactions with drugs metabolized by these enzymes.
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