Effect of camellia sinensis extract on the expression level of transcription factors and cytochrome p450 genes coding phase i drug-metabolizing enzymes

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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.

1. Zhang M, Binns CW, Lee AH. Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev 2002; 11:713-718.

2. Jian L, Xie LP, Lee AH, Binns CW. Protective effect of green tea against prostate cancer: a case-control study in southeast China Int J Cancer 2004; 108:130-135.

3. Foti RS, Wahlstrom JL. The role of dietary supplements in cytochrome P450-mediated drug interactions. Drug Metab Pharmacokinet 2008; 7:66-84.

4. Crespy V, Williamson G. A review of the health effects of green tea catechins in in vivo animal models. J Nutr 2004; 134:3431-3440.

5. Mukhtar H, Ahmad N. Green tea in chemoprevention of cancer. Toxicol Sci 1999; 52:111-117.

6. Higdong JV, Frei B. Tea catechins and polyphenols: health effects, metabolism and antioxidant functions. Crit Rev Food Sci Nutr 2003; 43:89-143.

7. Yu R, Jiao JJ, Duh JL, Gudehithlu K, Tan TH, Kong AN. Activation of mitogen-activated protein kinases by green tea polyphenols: Potential signaling pathways in the regulation of antioxidant-responsive element-mediated phase II enzyme gene expression. Carcinogenesis 1997; 18:451-456.

8. Gonzalez FJ, Tukey RH. Drug metabolism. In: Brunton LL, Lazo JS, Parker KL. (eds.), Goodman & Gilman’s the pharmacological basis of therapeutics. 11th ed. McGraw-Hill, New York 2006:71-91.

9. Riddick DS, Lee C, Bhathena A, Timist YE, Cheng PY, Morgan ET, et al. Transcriptional suppression of cytochrome P450 genes by endogenous and exogenous chemicals. Drug Metab Dispos 2004; 32:367-375.

10. Van Iersel ML, Verhagen H, van Bladeren PJ. The role of biotransformation in dietary (anti)carcinogenesis. Mutat Res 1999; 443:259-270.

11. Rushmore TH, Kong AN. Pharmacogenomics, regulation and signaling pathways of phase I and II drug metabolizing enzymes. Curr Drug Metab. 2002; 3:481-90.

12. Ribeiro A, Archer A, Beyec JL, Cattin AL, Saint-Just S, Pinçon-Raymond M, et al. Hepatic Nuclear Factor-4, a Key Transcription Factor at the Crossroads Between Architecture and Function of Epithelia. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery 2007; 1:166-175.

13. Mrozikiewicz PM, Bogacz A, Karasiewicz M, Mikolajczak PL, Ozarowski M, Seremak-Mrozikiewicz A, et al. The effect of standardized Echinacea purpurea extract on rat cytochrome P450 expression level. Phytomed 2010; 17:830-833.

14. Nakagawa T, Yokozawa T, Teresawa K, Shu S, Juneja LR. Protective activity of green tea against free radical- and glucose-mediated protein damage. J Agric Food Chem 2002; 50:2418-2422.

15. Nie G, Cao Y, Zhao B. Protective effects of green tea polyphenols and their major component, (-)-epigallocatechin-3-gallate (EGCG), on 6-hydroxydopamine-induced apoptosis in PC12 cells. Redox Rep 2002; 7:171-177.

16. Koo MWL, Cho ChH. Pharmacological effects of green tea on gastrointestinal system. Eur J Pharm 2004; 500:177-185.

17. Kim S, Lee MJ, Hong J, Li C, Smith TJ, Yang GY, et al. Plasma and tissue levels of tea catechins in rats and mice during chronic consumption of green tea polyphenols. Nutr Cancer 2000; 37:41-48.

18. Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, et al. Pharmacokinetics of tea catechins after ingestion of green tea and (-)- epigallocatechin-3 gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev 2002; 11:1025-1032.

19. Bu-Abbas A, Clifford MN, Walker R, Ioannides C. Selective induction of rat hepatic CYP1 proteins and of peroxisomal proliferation by green tea. Carcinogenesis 1994; 15:2575-2579.

20. Maliakal PP, Coville PF, Wanwimolruk S. Tea consumption modulates hepatic drug metabolizing enzymes in Wistar rats. J Pharm Pharmacol 2001; 53:569-577.

21. Misaka S, Kawabe K, Onoue S, Werba JP, Giroli M, Tamaki S, et al. Effects of Green Tea Catechins on Cytochrome P450 2B6, 2C8, 2C19, 2D6 and 3A Activities in Human Liver and Intestinal Microsomes. Drug Metab Pharmacokinet. 2012; doi; 10.2133/dmpk.DMPK-12-RG-101.

22. Misaka S, Kawabe K, Onoue S, Werba JP, Giroli M, Watanabe H, et al. Green Tea Extract Affects Cytochrome P450 3A Activity and Pharmacokinetics of Simvastatin in Rats. Drug Metab Pharmacokinet. 2013; doi; 10.2133/dmpk.DMPK-13-NT-006.

23. Nishikawa M, Ariyoshi N, Kotani A, Ishii I, Nakamura H, Nakasa H, et al. Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam. Drug Metab Pharmacokinet 2004; 19:280-289.

24. Mirkov S, Komorowski BJ, Ramirez J, Graber AY, Ratain MJ, Strom SC, et al. Effects of green tea compounds on irinotecan metabolism. Drug Metab Dispos 2007; 35:228-233.

25. Muto S, Fujita K, Yamazaki Y, Kamataki T. Inhibition by green tea catechins of metabolic activation of procarcinogens by human cytochrome P450. Mutat Res 2001; 479:197-206.

26. Donovan JL, Chavin KD, Devane CL, Taylor RM, Wang JS, Ruan Y, et al. Green tea (Camellia sinensis) extract does not alter cytochrome P450 3A4 or 2D6 activity in healthy volunteers. Drug Metab Dispos 2004; 32:906-908.

27. Chow HH, Hakim IA, Vining DR, Crowell JA, Cordova CA, Chew WM, et al. Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer Epidemiol Biomarkers Prev 2006; 15:2473-2476.

28. Niwattisaiwong N, Luo XX, Coville PF, Wanwimolruk S. Effects of Chinese, Japanese and Western tea on hepatic P450 enzyme activities in rats. Drug Metabol Drug Interact 2004; 20:43-56.

29. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol 2001; 53:1323-1329.

30. Williams SN, Shih H, Guenette DK, Brackney W, Denison MS, et al. Comparative studies on the effects of green tea extracts and individual tea catechins on human CYP1A gene expression. Chem Biol Interact 2000; 128:211-229.

31. Sohn S, Surace A, Fiala ES, Richie JP, Colosimo S, Zang E, et al. Effects of green and black tea on hepatic xenobiotic metabolizing systems in the male F344 rat. Xenobiotica 1994; 24:119-127.

32. Ayalogu EO, Snelling J, Lewis DF, Talwar S, Clifford MN, Ioannides C. Induction of hepatic CYP1A2 by the oral administration of caffeine to rats: lack of association with the Ah locus. Biochim Biophys Acta 1995; 1272:89-94.

33. Goasduff T, Dreano Y, Guillois B, Menez JF, Berthou F. Induction of liver and kidney CYP1A1/1A2 by caffeine in rat. Biochem Pharmacol 1996; 52:1915-1919.

34. Nikaidou S, Ishizuka M, Maeda Y, Hara Y, Kazusaka A, Fujita S. Effect of components of green tea extracts, caffeine and catechins on hepatic drug metabolizing enzyme activities and mutagenic transformation of carcinogens. Jpn J Vet Res 2005; 52:185-92.

35. Palermo CM, Westlake CA, Gasiewicz TA. Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein. Biochemistry 2005; 44:5041-52.

36. Bogacz A, Karasiewicz M, Kujawski R, Bartkowiak-Wieczorek J, Cichocka J, Kowalska A, et al. Molecular mechanisms of regulation of CYP enzymes of phase i metabolizm of xenobiotics - synthetic drugs and herbal preparations. Herba Pol 2012; 58:46-59.

37. Ibeanu GC, Goldstein JA. Transcriptional regulation of human CYP2C genes: functional comparison of CYP2C9 and CYP2C18 promoter regions. Biochemistry 1995; 34:8028-8036.

38. Chung I, Bresnick E. Regulation of the constitutive expression of the human CYP1A2 gene: Cis elements and their interactions with proteins. Mol Pharmacol 1995; 47:677-685.

39. Liu SY, Gonzalez FJ. Role of the liver-enriched transcription factor HNF-1 alpha in expression of the CYP2E1 gene. DNA Cell Biol 1995; 14:285-293.

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