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

• Autorzy: Bogacz A. , Karasiewicz M. , Bartkowiak-Wieczorek J. , Ozarowski M. , Seremak-Mrozikiewicz A. , Kujawski R. , Mikolajczak P. L. , Mrozikiewicz-Rakowska B. , Bobkiewicz-Kozlowska T. , Czerny B. , Grzeskowiak E. , Mrozikiewicz P. M.

Warianty tytułu

PL

Wpływ ekstraktu z Camellia sinensis na poziom ekspresji czynników transkrypcyjnych i genów cytochromu P450 kodujących enzymy I fazy metabolizmu leków

• Języki publikacji: EN

Abstrakty

EN

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.

PL

Zielona herbata (Camellia sinensis) jest powszechnie stosowana jako napój i suplement diety i może istotnie zmniejszać ryzyko wystąpienia wielu chorób. Pomimo powszechnego 59 Effect of Camellia sinensis extract on the expression level of transcription factors and cytochrome P450 genes coding... Vol. 59 No. 4 2013 zastosowania zielonej herbaty, dane dotyczące bezpieczeństwa jak i interakcji preparatu roślinnego i leku syntetycznego są bardzo ograniczone. Celem badania była ocena wpływu standaryzowanego ekstraktu z zielonej herbaty (GTE) zawierającego 61% katechin i 0,1% kofeiny na poziom ekspresji szczurzych genów CYP i czynników transkrypcyjnych stosując technikę real-time PCR. Wyniki wykazały, że GTE znacznie obniża poziom ekspresji CYP2C6 o 68% (p<0,001). W przypadku CYP3A1 i CYP3A2 poziom mRNA tych genów był również redukowany przez ekstrakt, ale w mniejszym stopniu w porównaniu do CYP2C6. Istotny wzrost w poziomie mRNA obserwowano dla czynników CAR, RXR i GR odpowiednio o 54% (p<0,05), 79% (p<0,001) i 23% (p<0,05) po 10 dniach stosowania ekstraktu. Dodatkowo, zanotowano niewielki wzrost poziomu ekspresji CYP1A1 o 21% (p>0,05). Brak istotnych różnic zaobserwowano dla CYP1A2 i CYP2D1/2. W badaniu wykazano również wzrost ilości transkryptu genu ARNT o 27% (p<0,05) podczas dłuższego stosowania. Ponadto, ekstrakt z zielonej herbaty wykazał zdolność do stymulacji HNF-1α zarówno po 3, jak i 10 dniach trwania eksperymentu odpowiednio o 30% (p<0,05) i 80% (p<0,001). Brak zmian obserwowano w przypadku stężenia cDNA dla HNF-4α. Wyniki te sugerują, że GTE może zmieniać ekspresję enzymów CYP, szczególnie w przypadku CYP2C6 (homolog ludzki CYP2C9) i może uczestniczyć w klinicznie istotnych reakcjach z lekami metabolizowanymi przez te enzymy.

Słowa kluczowe

EN

Camellia sinensis; green tea; plant extract; expression level; gene expression; transcription factor; cytochrome P450; gene coding; drug metabolism; enzyme

• Wydawca: -
• Czasopismo: Herba Polonica
• Rocznik: 2013
• Tom: 59
• Numer: 4
• Opis fizyczny: p.45-59,fig.,ref.

Twórcy

autor

Bogacz A.

• Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Sw.Marii Magdaleny 14, 61-861 Poznan, Poland
• Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland

autor

Karasiewicz M.

• Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland

autor

Bartkowiak-Wieczorek J.

• Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Sw.Marii Magdaleny 14, 61-861 Poznan, Poland
• Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland

autor

Ozarowski M.

• Department of Pharmacology and Experimental Biology, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland
• Department of Pharmaceutical Botany and Plant Biotechnology, Poznan University of Medical Sciences, Sw.Marii Magdaleny 14, 61-861 Poznan, Poland

autor

Seremak-Mrozikiewicz A.

• Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland

autor

Kujawski R.

• Department of Pharmacology and Experimental Biology, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland

autor

Mikolajczak P. L.

• Department of Pharmacology and Experimental Biology, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland
• Department of Pharmacology, Poznan University of Medical Sciences, Rokietnicka 5a, 60-806 Poznan, Poland

autor

Mrozikiewicz-Rakowska B.

• Department of Gastroenteorology and Metabolic Diseases, Medical University of Warsaw, Banacha 1a, 02-091 Warsaw, Poland

autor

Bobkiewicz-Kozlowska T.

• Department of Pharmacology, Poznan University of Medical Sciences, Rokietnicka 5a, 60-806 Poznan, Poland

autor

Czerny B.

• Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland
• Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, Zolnierska 48, 70-204 Szczecin, Poland

autor

Grzeskowiak E.

• Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Sw.Marii Magdaleny 14, 61-861 Poznan, Poland

autor

Mrozikiewicz P. M.

• Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Sw.Marii Magdaleny 14, 61-861 Poznan, Poland
• Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland

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Identyfikatory

DOI

10.2478/hepo-2013-0023