银杏叶提取物对细胞色素P450 影响的研究进展

摘要/Abstract

摘要： 银杏叶提取物(Ginkgo biloba extract, GBE)是目前使用最为广泛的中草药之一。GBE 与其他药物合用是否产生药物相互作用得到关注。GBE与其他药物合用, 可能通过影响肝药酶的活性发生药物相互作用, 其中GBE 对肝药酶的诱导或抑制作用的研究较为深入。本综述回顾了近年来报道的关于GBE 对细胞色素P450 CYP3A4、CYP2C9、CYP1A2、CYP2C19 的影响。

关键词: 银杏叶提取物, CYP3A4, CYP2C9, CYP1A2, CYP2C19

Abstract: Ginkgo biloba extract (GBE) is a popular herbal medicine and has received great attention in clinical therapy.Interactions between GBE and other drugs are of increasing concern.Among these interaction, induction and inhibition of hepatic drug metabolizing enzymes by GBE have been investigated. This review focuses mainly on research about the effects of GBE on CYP450:CYP3A4, CYP2C9, CYP1A2, CYP2C19.

Key words: Ginkgobilobaextracts, CYP3A4, CYP2C9, CYP1A2, CYP2C19

中图分类号:

R969

陶共由, 周宏灏. 银杏叶提取物对细胞色素P450 影响的研究进展[J]. 中国临床药理学与治疗学, 2008, 13(9): 1071-1075.

TAO Gong-you, ZHOU Hong-hao. Effects of Ginkgo biloba extracts on CYP450[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(9): 1071-1075.

参考文献

[1] 王金亭.银杏叶提取物的药用及食用价值 [J].食品与药品, 2006, 8(11):73-74.
[2] Chan PC, Xia Q, Fu PP.Ginkgo biloba leave extract:biological, medicinal, and toxicological effects [J].J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 2007, 25(3):211-244.
[3] Ahlemeyer B, Krieglstein J.Neuroprotective effects of Ginkgo biloba extract [J].Cell Mol Life Sci, 2003, 60 (9):1779-1792.
[4] Yoshikawa T, Naito Y, Kondo M.Ginkgo biloba leaf extract:review of biological actions and clinical applications [J].Antioxid Redox Signal, 1999, 1(4):469-480.
[5] ZhouW, Chai H, Lin PH, et al. Clinical use and molecular mechanisms of action of extract of Ginkgo biloba leaves in cardiovascular diseases [J].Cardiovasc Drug Rev, 2004, 22(4):309-319.
[6] Wijnen PA, Op den Buijsch RA, DrentM, et al. Review article:The prevalence and clinical relevance of cytochrome P450 polymorphisms [J].Aliment Pharmacol Ther, 2007, 26(2):211-219.
[7] Paine MF, KhalighiM, Fisher JM, et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism [J].J Pharmacol Exp Ther, 1997, 283(3):1552-1562.
[8] Motohiro KATO.Intestinal first-pass metabolism of CYP-3A4 substrates [J].Drug Metab Pharmacokinet, 2008, 23 (2):87-94.
[9] Ohnishi N, Kusuhara M, Yoshioka M, et al. Studies on interactions between functional foods or dietary supplements and medicines I.Effects of Ginkgo biloba Leaf Extract on the pharmacokinetics of diltiazem in rats [J].Biol Pharm Bull, 2003, 26(9):1315-1320.
[10] Yoshioka M, Ohnishi N, Sone N, et al. Studies on interactions between functional foods or dietary supplements and medicines III.Effects of Ginkgo biloba leaf extract on the pharmacokinetics of nifedipine in rats [J].Biol Pharm Bull, 2004, 27(12):2042-2045.
[11] Yang CY, Chao PDL, Hou YC, et al. Marked decrease of cy closporin bioavailability caused by coadministration of ginkgo and onion in rats [J].Food Chem Toxicol, 2006, 44(9):1572-1578.
[12] Shinozukaa K, Umegakic K, Kubotaa Y, et al. Feeding of Ginkgo biloba extract (GBE)enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats [J].Life Sci, 2002, 70(23): 2783-2792.
[13] Budzinski JW, Foster BC, Vandenhoek S, et al. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures [J]. Phytomedicine, 2000, 7(4):273-282.
[14] Yoshioka M, Ohnishi N, Koishi T, et al. Studies on interactions between functional foods or dietary supplements and medicines.IV.Effects of ginkgo biloba leaf extract on the pharmacokinetics and pharmacodynamics of nifedipine in healthy volunteers [J].Biol Pharm Bull, 2004, 27 (12):2006-2009.
[15] Markowitz JS, Donovan JL, Lindsay DeVane CL, et al. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers [J].J Clin Psychopharmacol, 2003, 23(6):576-581.
[16] Gurley BJ, Gardner SF, HubbardMA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans [J].Clin Pharmacol Ther, 2002, 72(3):276-287.
[17] Uchida S, Yamada H, Li XD, et al. Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers [J].Clin Pharmacol, 2006, 46(11):1290-1298.
[18] Topi'cE, Stefanovi'cM, Samardzija M.Association between the CYP2C9 polymorphism and the drug metabolism phenotype [J].Clin Chem LabMed, 2004, 42(1):72-78.
[19] Sugiyama T, Kubota Y, Shinozuka K, et al. Ginkgo biloba extract modifies hypoglycemic action of tolbutamide via hepatic cytochrome P450 mediated mechanism in aged rats [J].Life Sciences, 2004, 75(9):1113-1122.
[20] Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects [J].Br J Clin Pharmacol, 2005, 59(4):425-432.
[21] Mohutsky MA, Anderson GD, Miller JW, et al. Ginkgo biloba:Evaluation of CYP2C9 Drug Interactions In Vitro and In Vivo [J].Am J Ther, 2006, 13(1):24-31.
[22] Greenblatt DJ, von Moltke LL, Luo Y, et al. Ginkgo biloba does not alter clearance of Flurbiprofen, a cytochrome P450-2C9 substrate [J].J Clin Pharmacol, 2006, 46(2): 214-221.
[23] Yin OQ, Tomlinson B, Waye MM, et al. Pharmacogenetics and herb-drug interactions:experience with Ginkgo bilobaand omeprazole [J]. Pharmacogenetics, 2004, 14 (12):841-850.
[24] Landi MT, Sinha R, Lang NP, et al. Human cytochrome P4501A2 [J].IARC Sci Publ, 1999, (148):173-195.
[25] Umegaki K, Saito K, Kubota Y, et al. Ginkgo biloba extract markedly induces pentoxyresorufin O-dealkylase activity in rats [J].Jpn J Pharmacol, 2002, 90(4):345-351.
[26] Tang J, Sun J, Zhang Y, et al. Herb-drug interactions: Effect of Ginkgo biloba extract on the pharmacokinetics of theophylline in rats [J].Food Chem Toxicol, 2007, 45 (12):2441-2445.
[27] Yoshimoto K, Echizen H, Chiba K, et al. Identification of human CYP isoforms involved in the metabolism of propranolol enanfiomers N-desisopropylation is mediated mainly by CYP1A2 [J].Br J Clin Pharmacol, 1995, 39(4):421-431.
[28] 赵立子, 马锦芳, 邓颖, 等.银杏叶提取物对细胞色素 P450 酶CYP1A2 实验研究 [J].中国临床药理学杂志, 2005, 21(2):122-125.
[29] Li AP, Maurel P, Gomez-Lechon MJ, et al. Preclinical evaluatlon of drug-drug interaction potentiM:present status of the application of primary human hepatecytes in the evaluation of cytochrome P450 induction [J].Chem Biol Interact, l997, 107(1/2):5-16.