Research approaches of CYP450s' induction/inhibition and their application on drug development

Abstract

Abstract: Cytochrome P450 (CYP450) is the most important enzyme family in liver which plays a crucial role in metabolism of the exogenous and endogenous substances. The change of CYP450s on activity or content is closely related with the effectiveness and safety of their substrate drugs through altering drugs' effective doses or response time. Therefore, it is an indispensable research during drug development to understand the potential induction or inhibition effects on CYP450 enzyme. This paper reviewed methodology development of degree evaluation, phenotype analysis and mechanistic investigation of CYP450 enzyme induction/inhibition, as well as their application mainly on natural products.

Key words: Cytochrome P450, Induction/inhibition, Research approaches, Drug development, Natural products

CLC Number:

R969.1

BU Ming-hua, ZHANG Ying , LIU Jian-xun , LIU Dong-chun. Research approaches of CYP450s' induction/inhibition and their application on drug development[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(5): 579-585.

References

[1] 汪颖,杜丽娜.靶向细胞色素P450酶系:抗肿瘤药物发展的新思路[J].国际药学研究杂志,2008,35(1):62-64.
[2] 李雪,宋卉.反式白藜芦醇及反式白藜芦醇苷对大鼠肝微粒体蛋白质及细胞色素P450的影响[J].汕头大学医学院学报,2008,21(3):132-134,145.
[3] 和凡,钟国平,赵立子,等.丹参酮Ⅱ_A对大鼠细胞色素P450酶的诱导作用[J].中草药,2009,40(6):938-942.
[4] 涂自良,张澈,王启斌,等.葛根素对人肝微粒体中细胞色素P450酶活性的影响[J].中国药师,2008,11(2):131-134.
[5] 崔升淼,赵春顺,高坤,等.大鼠肝微粒体中葛根素的液相色谱-质谱测定法及药物代谢动力学[J].沈阳药科大学学报,2007,24(1):32-36.
[6] Liu Y, Zhang J, Li W,et al.Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes[J].Toxicol Sci, 2006,91 (2):356-364.
[7] 刘琳娜,王汝涛,王庆伟,等.甘草水煎液对大鼠肝微粒体细胞色素P450酶活性的影响[J].中国临床药理学与治疗学,2010,15(12):1330-1333.
[8] 刘高峰, 甄立棉, 黄丽军.丹参注射液对家兔体内CYP1A2、CYP2D6和CYP3A4活性的影响[J].中国临床药理学与治疗学,2010,15(7):775-780.
[9] 高志伟,施孝金,余琛,等.混合探针底物法同时预测细胞色素P450酶5种亚型的抑制作用[J].药学学报,2007,42(6):589-594.
[10] 雷霆雯,李红梅,许庆忠,等.大青叶对CYP1A1酶活性及转录水平影响[J].中国公共卫生,2006,(10):1241-1242.
[11] Medina-Díaz IM,Estrada-Mu?iz E,Reyes-Hernández OD,et al.Arsenite and its metabolites, MMAIII and DMAIII, modify CYP3A4, PXR and RXR alpha expression in the small intestine of CYP3A4 transgenic mice[J]. Toxicol Appl Pharmacol,2009, 239(2):162-168.
[12] Zimmermann C, Waterschoot R, Harmsen S,et al.PXR-mediated induction of human CYP3A4 and mouse Cyp3a11 by the glucocorticoid budesonide[J].Eur J Pharm Sci, 2009,36(4/5):565-571.
[13] Yu CN,Ye SS, Sun HY, et al.PXR-mediated transcriptional activation of CYP3A4 by cryptotanshinone and tanshinone IIA[J]. Chem Biol Interact,2009,177(1):58-64.
[14] Weems J,Yost G.3-Methylindole Metabolites Induce Lung CYP1A1 and CYP2F1 Enzymes by AhR and Non-AhR Mechanisms, Respectively[J].Chem Res Toxicol, 2010,23(3):696-704.
[15] Cooper B, Cho T, Thompson P, et al. Phthalate induction of CYP3A4 is dependent on glucocorticoid regulation of PXR expression[J]. Toxicol Sci,2008,103(2):268-277.
[16] 高晓新,郑素勤.中西药并用对细胞色素P450酶系的影响[J].华北煤炭医学院学报,2006,8(3):333-335.
[17] 曹亚杰,曹伟,余奇,等.吴茱萸次碱在人肝微粒体中对细胞色素P450酶的抑制作用[J].中南药学,2005,3(4):243-245.
[18] Kimura Y, Ito H, Ohnishi R, et al. Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity[J]. Food Chem Toxicol,2010,48(1):429-435.
[19] 邓颖,赵立子,毕惠嫦,等.银杏叶提取物及其萜类单体对人孕烷X受体介导CYP3A4转录的调节作用[J].中药新药与临床药理,2009,20(3):234-237.
[20] 邵敬伟, 董海燕,王涛,等.中药莪术激活PXR及对大鼠肝细胞色素P450 3A的影响[J].中国药理学通报,2008,24(4):504-509.
[21] Wang K, Chen S, Xie W,et al. Retinoids induce cytochrome P450 3A4 through RXR/VDR-mediated pathway[J].Biochem Pharmacol,2008,75(11):2204-2213.
[22] Chen S, Wang K, Wan Y.Retinoids activate RXR/CAR-mediated pathway and induce CYP3A[J].Biochem Pharmacol,2010,79(2):270-276.
[23] Istrate M, Nussler A, Eichelbaum M, et al.Regulation of CYP3A4 by pregnane X receptor: The role of nuclear receptors competing for response element binding[J]. Biochem Biophys Res Commun,2010,393(4):688-693.
[24] Yoshinari K, Yoda N, Toriyabe T, et al.Constitutive androstane receptor transcriptionally activates human CYP1A1 and CYP1A2 genes through a common regulatory element in the 5'-flanking region[J].Biochem Pharmacol,2010,79(2):261-269.
[25] Toriyabe T, Nagata K, Takada T, et al.Unveiling a new essential cis element for the transactivation of the CYP3A4 gene by xenobiotics[J].Mol Pharmacol, 2009,75(3):677-684.
[26] Pavek P, Pospechova K, Svecova L, et al.Intestinal cell-specific vitamin D receptor (VDR) -mediated transcriptional regulation of CYP3A4 gene[J].Biochem Pharmacol, 2010, 79(2):277-287.
[27] Akagi S, Nakajima M, Mohri T, et al.Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4[J].J Biol Chem,2008,283(15):9674-9680.
[28] Roth A, Looser R, Kaufmann M, et al.Sterol regulatory element binding protein 1 interacts with pregnane X receptor and constitutive androstane receptor and represses their target genes[J].Pharmacogenet Genomics,2008,18(4):325-337.
[29] Liu F, Song X, Yang D, et al.The far and distal enhancers in the CYP3A4 gene co-ordinate the proximal promoter in responding similarly to the pregnane X receptor but differentially to hepatocyte nuclear factor-4alpha[J].Biochem J,2008,409:243-250.
[30] Cerveny L, Svecova L, Anzenbacherova E, et al.Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways[J].Drug Metabo Dispos,2007,35(7):1032-1041.
[31] Fang H, Strom S, Ellis E, et al. Positive and negative regulation of human hepatic hydroxysteroid sulfotransferase (SULT2A1) gene transcription by rifampicin: roles of hepatocyte nuclear factor 4α and pregnane X receptor[J].J Pharmacol Exp Ther, 2007,323(2):586-598.