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

页码：218 / 229

页数：12

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