Bioactive terpenoids and flavonoids from Ginkgo Biloba extract induce the expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptor-mediated pathways

Pharmaceutical Research

Volumn 26, Issue 4, 2009, Pages 872-882

  Li, Linhao ^a   Stanton, Joseph D ^a   Tolson, Antonia H ^a   Luo, Yuan ^a   Wang, Hongbing ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY   (United States)

Author keywords

AhR; CAR; Cytochrome P450; EGb 761; PXR

Indexed keywords

AROMATIC HYDROCARBON RECEPTOR; BILOBALIDE; CONSTITUTIVE ANDROSTANE RECEPTOR; CYTOCHROME P450 2B6; CYTOCHROME P450 3A4; DRUG METABOLIZING ENZYME; FLAVONOID; GINKGO BILOBA EXTRACT; GINKGOLIDE A; GINKGOLIDE B; GINKGOLIDE C; GLUCURONOSYLTRANSFERASE 1A1; KAEMPFEROL; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; PREGNANE X RECEPTOR; QUERCETIN; TAMARIXETIN; TERPENOID; UNCLASSIFIED DRUG; XENOBIOTIC AGENT;

ARTICLE; CONTROLLED STUDY; DRUG STRUCTURE; ENZYME ACTIVATION; ENZYME INDUCTION; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; LIVER CELL CULTURE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REPORTER GENE; TRANSIENT TRANSFECTION;

ARYL HYDROCARBON HYDROXYLASES; ATP-BINDING CASSETTE TRANSPORTERS; CELL LINE, TUMOR; CELLS, CULTURED; CYTOCHROME P-450 CYP3A; ENZYME INDUCTION; ENZYMES; FLAVONOIDS; GENES, REPORTER; GLUCURONOSYLTRANSFERASE; HEPATOCYTES; HUMANS; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; OXIDOREDUCTASES, N-DEMETHYLATING; P-GLYCOPROTEIN; PLANT EXTRACTS; RECEPTORS, ARYL HYDROCARBON; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, STEROID; RNA, MESSENGER; TERPENES; TRANSCRIPTION FACTORS; TRANSFECTION; UP-REGULATION;

EID: 61449220882     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-008-9788-8     Document Type: Article

References (43)

1. E. P. Elovic R. D. Zafonte 2001 Ginkgo biloba: applications in traumatic brain injury J. Head Trauma Rehabil. 16 603 607
2. F. V. DeFeudis. Ginkgo biloba extract (EGb 761): from chemistry to clinic. Publi Ullstein Med (1998).
3. J. V. Smith Y. Luo 2004 Studies on molecular mechanisms of Ginkgo biloba extract Appl. Microbiol. Biotechnol. 64 465 472
4. S. Jaracz S. Malik K. Nakanishi 2004 Isolation of ginkgolides A, B, C, J and bilobalide from G. biloba extracts Phytochemistry. 65 2897 2902
5. P. F. Smith K. Maclennan C. L. Darlington 1996 The neuroprotective properties of the Ginkgo biloba leaf: a review of the possible relationship to platelet-activating factor (PAF) J. Ethnopharmacol. 50 131 139
6. J. V. Smith Y. Luo 2003 Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761 J. Alzheimers Dis. 5 287 300
7. S. M. Robertson R. T. Davey J. Voell E. Formentini R.M. Alfaro S. R. Penzak 2008 Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects Curr. Med. Res. Opin. 24 591 599
8. B. J. Gurley S. F. Gardner M. A. Hubbard D. K. Williams W. B. Gentry Y. Cui C. Y. Ang 2002 Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans Clin. Pharmacol. Ther. 72 276 287
9. K. Shinozuka K. Umegaki Y. Kubota N. Tanaka H. Mizuno J. Yamauchi K. Nakamura M. Kunitomo 2002 Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats Life Sciences. 70 2783 2792
10. Y. Deng H. C. Bi L. Z. Zhao F. He Y.Q. Liu J. J. Yu Z. M. Ou L. Ding X. Chen Z. Y. Huang M. Huang S. F. Zhou 2008 Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats Xenobiotica. 38 465 481
11. T. K. Chang J. Chen E. Y. Yeung 2006 Effect of Ginkgo biloba extract on procarcinogen-bioactivating human CYP1 enzymes: identification of isorhamnetin, kaempferol, and quercetin as potent inhibitors of CYP1B1 Toxicol. Appl. Pharmacol. 213 18 26
12. T. K. Chang J. Chen X.W. Teng 2006 Distinct role of bilobalide and ginkgolide A in the modulation of rat CYP2B1 and CYP3A23 gene expression by Ginkgo biloba extract in cultured hepatocytes Drug Metabolism and Disposition: the Biological Fate of Chemicals. 34 234 242
13. G. Rajaraman J. Chen T. K. Chang 2006 Ginkgolide A contributes to the potentiation of acetaminophen toxicity by Ginkgo biloba extract in primary cultures of rat hepatocytes Toxicol. Appl. Pharmacol. 217 225 233
14. T. W. Synold I. Dussault B. M. Forman 2001 The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux Nat. Med. 7 584 590
15. E. L. LeCluyse 2001 Pregnane X receptor: molecular basis for species differences in CYP3A induction by xenobiotics Chem. Biol. Interact. 134 283 289
16. H. Wang E. L. LeCluyse 2003 Role of orphan nuclear receptors in the regulation of drug-metabolising enzymes Clin. Pharmacokinet. 42 1331 1357
17. J. Sugatani H. Kojima A. Ueda S. Kakizaki K. Yoshinari Q. H. Gong I. S. Owens M. Negishi T. Sueyoshi 2001 The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR Hepatology Baltimore, Md. 33 1232 1238
18. M. F. Yueh Y. H. Huang A. Hiller S. Chen N. Nguyen R. H. Tukey 2003 Involvement of the xenobiotic response element (XRE) in Ah receptor-mediated induction of human UDP-glucuronosyltransferase 1A1 J. Biol. Chem. 278 15001 15006
19. S. T. DeKosky A. Fitzpatrick D. G. Ives J. Saxton J. Williamson O. L. Lopez G. Burke L. Fried L. H. Kuller J. Robbins R. Tracy N. Woolard L. Dunn R. Kronmal R. Nahin C. Furberg 2006 The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia Contemporary clinical trials. 27 238 253
20. H. Wang S. Faucette T. Sueyoshi R. Moore S. Ferguson M. Negishi E. L. LeCluyse 2003 A novel distal enhancer module regulated by pregnane X receptor/constitutive androstane receptor is essential for the maximal induction of CYP2B6 gene expression J. Biol. Chem. 278 14146 14152
21. E. L. LeCluyse E. Alexandre G. A. Hamilton C. Viollon-Abadie D. J. Coon S. Jolley L. Richert 2005 Isolation and culture of primary human hepatocytes Methods Mol. Biol. 290 207 229
22. L. Li T. Chen J. D. Stanton T. Sueyoshi M. Negishi H. Wang 2008 The peripheral benzodiazepine receptor ligand 1-(2-chlorophenyl-methylpropyl)-3- isoquinoline-carboxamide is a novel antagonist of human constitutive androstane receptor Mol. Pharmacol. 74 443 453
23. C. M. Smith R. A. Graham W. L. Krol I. S. Silver M. Negishi H. Wang E. L. Lecluyse 2005 Differential UGT1A1 induction by chrysin in primary human hepatocytes and HepG2 Cells The Journal of Pharmacology and Experimental Therapeutics. 315 1256 1264
24. M. Nishimura H. Yoshitsugu S. Naito I. Hiraoka 2002 Evaluation of gene induction of drug-metabolizing enzymes and transporters in primary culture of human hepatocytes using high-sensitivity real-time reverse transcription PCR Yakugaku Zasshi. 122 339 361
25. J. M. Maglich C. M. Stoltz B. Goodwin D. Hawkins-Brown J. T. Moore S. A. Kliewer 2002 Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification Mol. Pharmacol. 62 638 646
26. S. R. Faucette T. C. Zhang R. Moore T. Sueyoshi C. J. Omiecinski E. L. LeCluyse M. Negishi H. Wang 2007 Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers J. Pharmacol. Exp. Ther. 320 72 80
27. E. L. LeCluyse 2001 Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation Eur. J. Pharm. Sci. 13 343 368
28. E. A. Roberts K. C. Johnson P. A. Harper A. B. Okey 1990 Characterization of the Ah receptor mediating aryl hydrocarbon hydroxylase induction in the human liver cell line Hep G2 Arch. Biochem. Biophys. 276 442 450
29. F. Rencurel A. Stenhouse S. A. Hawley T. Friedberg D. G. Hardie C. Sutherland C. R. Wolf 2005 AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line J. Biol. Chem. 280 4367 4373
30. G. Lemaire G. de Sousa R. Rahmani 2004 A PXR reporter gene assay in a stable cell culture system: CYP3A4 and CYP2B6 induction by pesticides Biochem. Pharmacol. 68 2347 2358
31. J. M. Lehmann D. D. McKee M. A. Watson T. M. Willson J. T. Moore S. A. Kliewer 1998 The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions The Journal of Clinical Investigation. 102 1016 1023
32. B. Goodwin E. Hodgson D. J. D'Costa G.R. Robertson C. Liddle 2002 Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor Mol. Pharmacol. 62 359 365
33. A. P. Li P. Maurel M. J. Gomez-Lechon L. C. Cheng M. Jurima-Romet 1997 Preclinical evaluation of drug-drug interaction potential: present status of the application of primary human hepatocytes in the evaluation of cytochrome P450 induction Chem. Biol. Interact. 107 5 16
34. N. He H. B. Cai H. G. Xie X. Collins T. I. Edeki S. C. Strom 2007 Induction of cyp3a in primary cultures of human hepatocytes by ginkgolides a and B Clin. Exp. Pharmacol. Physiol. 34 632 635
35. Y. Deng H. Bi L. Zhao X. Wang J. Chen Z. Ou L. Ding L. Xu S. Guan X. Chen S. Zhou M. Huang 2008 Induction of cytochrome P450 3A by the Ginkgo biloba extract and bilobalides in human and rat primary hepatocytes Drug Metab. Lett. 2 60 66
36. W. Xie M. F. Yeuh A. Radominska-Pandya S. P. Saini Y. Negishi B. S. Bottroff G. Y. Cabrera R. H. Tukey R. M. Evans 2003 Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor Proc. Natl. Acad. Sci. U S A. 100 4150 4155
37. S. S. Auerbach M. A. Stoner S. Su C. J. Omiecinski 2005 Retinoid X receptor-alpha-dependent transactivation by a naturally occurring structural variant of human constitutive androstane receptor (NR1I3) Mol. Pharmacol. 68 1239 1253
38. H. Satsu Y. Hiura K. Mochizuki M. Hamada M. Shimizu 2008 Activation of pregnane X receptor and induction of MDR1 by dietary phytochemicals J. Agric. Food Chem. 56 5366 5373
39. E. Y. Yeung T. Sueyoshi M. Negishi T. K. Chang 2008 Identification of Ginkgo biloba as a novel activator of pregnane X receptor Drug Metabolism and Disposition: the Biological Fate of Chemicals. 36 2270 2276
40. K. Umegaki Y. Taki K. Endoh K. Taku H. Tanabe K. Shinozuka T. Sugiyama 2007 Bilobalide in Ginkgo biloba extract is a major substance inducing hepatic CYPs J. Pharm. Pharmacol. 59 871 877
41. B. H. Hellum Z. Hu O. G. Nilsen 2007 The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes Basic Clin. Pharmacol. Toxicol. 100 23 30
42. A. L. Sesink K. A. O'Leary P. C. Hollman 2001 Quercetin glucuronides but not glucosides are present in human plasma after consumption of quercetin-3-glucoside or quercetin-4'-glucoside The Journal of Nutrition 131 1938 1941
43. E. U. Graefe J. Wittig S. Mueller A. K. Riethling B. Uehleke B. Drewelow H. Pforte G. Jacobasch H. Derendorf M. Veit 2001 Pharmacokinetics and bioavailability of quercetin glycosides in humans J. Clin. Pharmacol. 41 492 499