Impact of Panax ginseng and Ginkgo biloba extracts on expression level of transcriptional factors and xenobiotic-metabolizing cytochrome P450 enzymes

Open access


Introduction: Despite widespread use of Panax ginseng and Ginkgo biloba, the data on the safety as well as herb-drug interactions are very limited. Therefore, we postulate that P. ginseng and G. biloba may modulate the activity and content of cytochrome P450 isozymes involved in the biotransformation of diverse xenobiotic substances. Objective: The aim of our study was to determine the influence of herbal remedies on the expression level of CYP enzymes and transcriptional factors. Methods: Male Wistar rats were given standardized Panax ginseng (30 mg/kg p.o.) or standardized Ginkgo biloba (200 mg/kg p.o.) for 3 and 10 days. The expression in liver tissue was analyzed by realtime PCR method. Results: Our results showed a decrease of CYP3A1 (homologue to human CYP3A4) mRNA level after P. ginseng extract treatment. The CYP2C6 (homologue to human CYP2C9) expression was also reduced. Additionally, after 10 days of the treatment with P. ginseng an increase of CYP1A1 (homologue to human CYP1A1) and CYP1A2 (homologue to human CYP1A2) expression was observed. Moreover, G. biloba extract also caused an increase of expression level for CYP1A1, CYP2C6, CYP3A1 and CYP3A2. Conclusion: Our findings suggest that herbal extracts can modulate the expression of transcriptional factors and CYP enzymes involved in xenobiotic metabolism and chemical carcinogenesis.

1. Benishin CG. Actions of ginsenoside Rb1 on choline uptake in central cholinergic nerve endings. Neurochem Int 1992; 21:1-5. doi:

2. Dorman T. Herbal medicine and anesthesia. Curr Opin Anaesthesiol 2001; 14:667-669.

3. Wakabayashi C, Murakami K, Hasegawa H, Murata J, Saiki I. An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun 1998; 246:725-730. doi:

4. Entschladen F, Drell TL, Lang K, Joseph J, Zaenker KS. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters. Lancet Oncol 2004; 5:254-258. doi:

5. Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 1997; 54:1-8. doi: http://

6. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs 2009; 69:1777-1798. doi:

7. Birks J, Grimley EJ. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2007; 2: CD003120. doi:

8. Fessenden JM, Wittenbern W, Clarke L. Ginkgo biloba. A case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy. Am Surg 2001; 67:33-35.

9. Ribeiro A, Archer A, Beyec JL, Cattin AL, Saint-Just S, Pinçon-Raymond M et al. Nuclear factor-4, a key transcription factor at the crossroads between architecture and function of epithelia. Recent Patents on Endocrine. Metab Immune Drug Discov 2007; 1:166-175. doi:

10. European Pharmacopoeia. 6th ed/ European directorate for the quality of medicines and healthcare, Strasbourg, 2008; 2:1969-2959.

11. 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. doi:

12. Chang TK, Chen J, Benetton SA. In vitro effect of standardized ginseng extracts and individual ginsenosides on the catalytic activity of human CYP1A1, CYP1A2, and CYP1B1. Drug Metab Dispos 2002; 30: 378-384. doi:

13. Yune-Fang U, Yun-Lian L. Effects of ginsenoside Rd and Panax ginseng extract on Cyp1a, Cyp2b, Cyp2c, Cyp2e1, and Cyp3a activities in C57BL/6JNarl mice. J Chin Med 2012; (3,4):143-152.

14. Nguyen TD, Villard PH, Barlatier A, Elsisi AE, Jouve E, Duc NM et al. Panax vietnamensis protects mice against carbon tetrachloride-induced hepatotoxicity without any modification of CYP2E1 gene expression. Planta Med 2000; 66:714-719. doi:

15. Lee HC, Hwang SG, Lee YG, Sohn HO. Lee DW, Hwang SY et al. In vivo effects of Panax ginseng extracts on the cytochrome P450-dependent monooxygenase system in the liver of 2,3,7,8-tetrachlorodibenzo-p-dioxinexposed guinea pig. Life Sci 2002; 71:759-769. doi:

16. Lee JH, Sul D, Oh E, Jung WW, Jung WW, Hwang KW et al. Panax ginseng effects on DNA damage, CYP1A1 expression and histopathological changes in testes of rats exposed to 2,3,7,8-tetrachlorodibenzo-pdioxin. Food Chem Toxicol 2007; 45:2237-2244.

17. Ribonnet L, Callebaut A, Nobels I, Scippo ML, Schneider YJ, De Saeger S et al. Modulation of CYP1A1 activity by a Ginkgo biloba extract in the human intestinal Caco-2 cells. Toxicol Lett 2011; 202:193-202. doi:

18. Kuo IF, Chen J, Chang TK. Effect of Ginkgo biloba extract on rat hepatic microsomal CYP1A activity: role of ginkgolides, bilobalide, and flavonols. Can J Physiol Pharmacol 2004; 82:57-64. doi:

19. von Moltke LL, Weemhoff JL, Bedir E, Khan IA, Harmatz JS, Goldman P et al. Inhibition of human cytochromes P450 by components of Ginkgo biloba. J Pharm Pharmacol 2004 56:1039-1044. doi:

20. Deng Y, Bi HC, Zhao LZ, Wang XD, Chen J, Ou ZM et al. Induction of cytochrome P450 3A by the Ginkgo biloba extract and bilobalides in human and rat primary hepatocytes. Drug Metab Lett 2008; 2: 60-66. doi:

21. Deng Y, Bi HC, Zhao LZ, He F, Liu YQ, Yu JJ et al. Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats. Xenobiotica 2008; 38:465-481. doi: http://

22. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002; 72:276-287. DOI: 10.1067/mcp.2002.126913

23. Markowitz JS, Donovan JL, Lindsay DeVane C, Sipkes L, Chavin KD. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers. J Clin Psychopharmacol 2003; 23: 576-581. doi:

Herba Polonica

From Botanical to Medical Research

Journal Information

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 253 250 19
PDF Downloads 92 91 7