紫锥菊通过激活孕烷X受体途径上调CYP1A2、CYP3A4和MDR1基因表达。
Echinacea purpurea up-regulates CYP1A2, CYP3A4 and MDR1 gene expression by activation of pregnane X receptor pathway.
作者信息
Awortwe Charles, Manda Vamshi K, Avonto Cristina, Khan Shabana I, Khan Ikhlas A, Walker Larry A, Bouic Patrick J, Rosenkranz Bernd
机构信息
Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch , Cape Town , South Africa .
出版信息
Xenobiotica. 2015 Mar;45(3):218-29. doi: 10.3109/00498254.2014.973930. Epub 2014 Nov 7.
Abstract
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 F1, F2 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.
摘要
- 本研究从人孕烷X受体（PXR）激活的角度，探讨紫锥菊介导诱导CYP1A2、CYP3A4和MDR1的潜在机制。2. 通过报告基因检测法，在HepG2细胞中测试紫锥菊粗提物和提取物的PXR激活情况。采用定量实时聚合酶链反应来确定它们对CYP1A2和CYP3A4信使核糖核酸表达的影响。根据为各细胞色素确定的半数有效浓度值，将胶囊和提取物的药物代谢酶诱导风险分为高、中、低三类。3. 提取物F1、F2和胶囊（2660）强烈激活PXR，活性分别增加5倍、4倍和3.5倍。紫锥菊制剂通过PXR激活增强CYP1A2、CYP3A4和MDR1的上调。4. 因此，紫锥菊制剂通过PXR激活上调CYP1A2、CYP3A4和P-糖蛋白，从而导致药草-药物相互作用。
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