Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products.
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 (48 h). 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.
Budzinski
Jason W
JW
Centre for Research in Biopharmaceuticals and Biotechnology, University of Ottawa, Ottawa, ON K1N6N5, Canada.
Trudeau
Vance L
VL
Drouin
Cathy E
CE
Panahi
Mitra
M
Arnason
J Thor
JT
Foster
Brian C
BC
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000498:Allyl Compounds; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D018938:Caco-2 Cells; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004149:Dioxoles / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D006801:Humans; D039321:Hydrastis; D020944:Silybum marianum; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019258:Saquinavir / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000498:Allyl Compounds; D000972:Antineoplastic Agents, Phytogenic; D002214:Capsules; D004149:Dioxoles; D017320:HIV Protease Inhibitors; D010936:Plant Extracts; C498255:5-allyl 6,7-dimethoxy 1,3-benzodioxole; D014747:Vinblastine; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019258:Saquinavir