Authors: Trudeau, Vance L.; Drouin, Cathy E.; Panahi, Mitra; Arnason, J. T.; Foster, Brian C.; Budzinski, Jason W.

Source: Canadian Journal of Physiology and Pharmacology, Volume 85, Number 9, September 2007 , pp. 966-978(13)

Publisher: NRC Research Press

Abstract:

In this study, we used an in vitro Caco-2 cell monolayer model to evaluate aqueous extracts of commercial-source goldenseal (Hydrastis canadensis) and milk thistle (Silybum marianum) capsule formulations, their marker phytochemicals (berberine and silibinin, respectively), as well as dillapiol, vinblastine, and the HIV protease inhibitor saquinavir for their ability to modulate CYP3A4 and ABCB1 expression after short-term exposure (48h). Both upregulation and downregulation of CYP3A4 expression was observed with extracts of varying concentrations of the two natural health products (NHPs). CYP3A4 was highly responsive in our system, showing a strong dose-dependent modulation by the CYP3A4 inhibitor dillapiol (upregulation) and the milk thistle flavonolignan silibinin (downregulation). ABCB1 was largely unresponsive in this cellular model and appears to be of little value as a biomarker under our experimental conditions. Therefore, the modulation of CYP3A4 gene expression can serve as an important marker for the in vitro assessment of NHP-drug interactions.

Dans la présente étude, on a examiné divers extraits aqueux de formulations en capsule de chardon Marie (Silybum marianum) et d'hydraste du Canada (Hydrastis canadensis) de source commerciale, leurs constituants phytochimiques (berbérine et silibinine respectivement) dillapiol, vinblastine, et l'inhibiteur de la protéase du HIV saquinavir afin d'évaluer leur capacité à moduler l'expression de CYP3A4 et ABCB1 dans des monocouches de cellules Caco-2 après une exposition de courte durée (48 heures). Les extraits aqueux de diverses concentrations des deux produits de santé naturels (PSN) ont modulé dans une large mesure l'expression du CYP3A4, puisqu'une augmentation et une diminution ont été observées. En règle générale, CYP3A4 a fortement réagi dans notre système, tel qu'indiqué par une modulation dose-dépendante importante par l'inhibiteur de CYP3A4 dillapiol (augmentation) et la flavolignane silibinine du chardon Marie (diminution). ABCB1 a faiblement réagi dans ce modèle cellulaire et offre peu d'intérêt comme biomarqueur dans nos conditions expérimentales. Ainsi, la modulation de l'expression du gène CYP3A4 pourrait être un marqueur important pour l'évaluation in vitro des interactions PSN-médicaments.

Document Type: Research article

Publication date: 2007-09-01

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• In this Subject: Anatomy & Physiology ,  Pharmacology
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