Echinacea purpurea up-regulates CYP1A2, CYP3A4 and MDR1 gene expression by activation of pregnane X receptor pathway

被引：29
|
作者：
Awortwe, Charles [1 ]
Manda, Vamshi K. [2 ]
Avonto, Cristina [2 ]
Khan, Shabana I. [2 ,3 ]
Khan, Ikhlas A. [2 ,3 ]
Walker, Larry A. [2 ,4 ]
Bouic, Patrick J. [5 ,6 ]
Rosenkranz, Bernd [1 ]
机构：
[1] Univ Stellenbosch, Fac Med & Hlth Sci, Div Clin Pharmacol, Cape Town, South Africa
[2] Univ Mississippi, Natl Ctr Nat Prod Res, Sch Pharm, Oxford, MS USA
[3] Univ Mississippi, Sch Pharm, Dept Biomol Sci, Div Pharmacognosy, Oxford, MS USA
[4] Univ Mississippi, Sch Pharm, Dept Biomol Sci, Div Pharmacol, Oxford, MS USA
[5] Synexa Life Sci, Montague Gardens, Cape Town, South Africa
[6] Univ Stellenbosch, Fac Med & Hlth Sci, Div Med Microbiol, Cape Town, South Africa
来源：
XENOBIOTICA | 2015年 / 45卷 / 03期
基金：
美国农业部;
关键词：
Activation; cytochrome P450 enzymes (CYPs); E; purpurea; human liver carcinoma (HepG2); human pregnane xenobiotic receptor (hPXR); DRUG-METABOLIZING-ENZYMES; ST-JOHNS-WORT; IN-VITRO; PHARMACEUTICAL RESEARCH; CYTOCHROME-P450; INDUCTION; MANUFACTURERS;
D O I：
10.3109/00498254.2014.973930
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
1. This study investigated the mechanism underlying Echinacea-mediated induction of CYP1A2, CYP3A4 and MDR1 in terms of human pregnane X receptor (PXR) activation. 2. Crude extracts and fractions of Echinacea purpurea were tested for PXR activation in HepG2 cells by a reporter gene assay. Quantitative real-time PCR was carried out to determine their effects on CYP1A2 and CYP3A4 mRNA expressions. Capsules and fractions were risk ranked as high, intermediate and remote risk of drug-metabolizing enzymes induction based on EC50 values determined for respective CYPs. 3. Fractions F-1, F-2 and capsule ( 2660) strongly activated PXR with 5-, 4- and 3.5-fold increase in activity, respectively. Echinacea preparations potentiated up-regulation of CYP1A2, CYP3A4 and MDR1 via PXR activation. 4. Thus E. purpurea preparations cause herb-drug interaction by up-regulating CYP1A2, CYP3A4 and P-gp via PXR activation.
引用
收藏
页码：218 / 229
页数：12
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