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

Awortwe, Charles; Manda, Vamshi K.; Avonto, Cristina; Khan, Shabana I.; Khan, Ikhlas A.; Walker, Larry; Bouic, Patrick; Rosenkranz, Bernd

doi:10.3109/00498254.2014.973930

Cited by 32 publications

(28 citation statements)

References 37 publications

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“…The immune response of E. purpurea is to combat pathogen infections and enhance the activities of neutrophils, macrophages, poly morphonuclear leukocytes (PMN) and natural killer cells (NK) [ 7 ]. Especially in some African countries, it could have a great effect on treating patients who are infected with HIV [ 8 ]. Clinical trials have demonstrated that E. purpurea can be used for the treatment of cancer or provide a substitute treatment for cancer patients [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract

Wang

et al. 2017

Molecules

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A rapid and sensitive Ultra High Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed and validated to simultaneously determine the concentration of seven phenolic acids (syringic acid, ferulic acid, caffeic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid) in rat plasma after oral administration of Echinacea purpurea extract. After mixing with the internal standard (IS), butylparaben, plasma samples were prepared by liquid–liquid extraction with ethyl acetate. The separation was performed using the Agilent Eclipse Plus C18 column (1.8 μm, 2.1 mm × 50 mm) with a gradient system consisting of solution A (0.1% acetic acid in water) and solution B (methanol) at a flow rate of 0.3 mL/min. The detection was accomplished by a multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). The method was validated in terms of linearity, precision, accuracy, extraction recovery, matrix effect and stability. This method was successfully applied to study the pharmacokinetic properties of the seven compounds after oral administration of Echinacea purpurea extract in rats.

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Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract

Wang

et al. 2017

Molecules

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“…An in vitro study showing the effects of an Echinacea preparation and isolated alkylamides on CYP3A4 expression did not document any statistically significant changes in the mRNA steady-state level of CYP3A4 after treating human hepatic cellular carcinoma HepG2 cells with clinically relevant concentrations of Echinaforce ® or any of the alkylamides [133]. Conversely, in the same cell line, positive results were obtained more recently that suggest gene expression up-regulation of metabolic enzyme and transporter by activation of PXR pathway [143,144]. In co-transfected HepG2 cells using the luciferase gene reporter assays, it was observed that Echinacea extract induced a time-and concentration-dependent activation of CYP3A4, CYP1A2 enzymes and the ABCB1 drug transporter [143].…”

Section: Echinaceamentioning

confidence: 92%

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance

Rombolà

Scuteri

Straface

et al. 2020

Life

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The therapeutic efficacy of a drug or its unexpected unwanted side effects may depend on the concurrent use of a medicinal plant. In particular, constituents in the medicinal plant extracts may influence drug bioavailability, metabolism and half-life, leading to drug toxicity or failure to obtain a therapeutic response. This narrative review focuses on clinical studies improving knowledge on the ability of selected herbal medicines to influence the pharmacokinetics of co-administered drugs. Moreover, in vitro studies are useful to anticipate potential herbal medicine-drug interactions. In particular, they help to elucidate the cellular target (metabolic or transporter protein) and the mechanism (induction or inhibition) by which a single constituent of the herbal medicine acts. The authors highlight the difficulties in predicting herbal–drug interactions from in vitro data where high concentrations of extracts or their constituents are used and pharmacokinetics are missed. Moreover, the difficulty to compare results from human studies where different kinds of herbal extracts are used is discussed. The herbal medicines discussed are among the best sellers and they are reported in the “Herbal Medicines for Human Use” section of the European Medicinal Agency (EMA).

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“…It is used to treat colds, upper respiratory infections, and dermatologic issues, and contains cichoric acid, caftaric acid, and echinacoside [ 84 , 85 , 86 ]. Crude extracts of Echinacea activate hPXR to induce CYP3A4 gene transcription and increase the mRNA of CYP1A2, CYP3A4, and MDR1 in the HepG2 cell line [ 87 ]. However, Echinacea extract may inhibit the rifampicin-mediated induction of CYP3A4 transcription via hPXR [ 45 ] and has been reported to inhibit CYP1A2 and CYP3A [ 41 , 42 ].…”

Section: Herbal Supplements With Potential P450-associated Hepatotmentioning

confidence: 99%

Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450

Brewer

Chen

2017

IJMS

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Herbal supplements are a significant source of drug-drug interactions (DDIs), herb-drug interactions, and hepatotoxicity. Cytochrome P450 (CYP450) enzymes metabolize a large number of FDA-approved pharmaceuticals and herbal supplements. This metabolism of pharmaceuticals and supplements can be augmented by concomitant use of either pharmaceuticals or supplements. The xenobiotic receptors constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) can respond to xenobiotics by increasing the expression of a large number of genes that are involved in the metabolism of xenobiotics, including CYP450s. Conversely, but not exclusively, many xenobiotics can inhibit the activity of CYP450s. Induction of the expression or inhibition of the activity of CYP450s can result in DDIs and toxicity. Currently, the United States (US) Food and Drug Administration does not require the investigation of the interactions of herbal supplements and CYP450s. This review provides a summary of herbal supplements that inhibit CYP450s, induce the expression of CYP450s, and/or whose toxicity is mediated by CYP450s.

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

Cited by 32 publications

References 37 publications

Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract

Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance

Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450

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