title: In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products.
abstract: Extracts of six commonly used commercially available herbal products, St. John's wort, common valerian, common sage, Ginkgo biloba, Echinacea purpurea and horse chestnut were investigated for their in vitro inhibitory potential of CYP3A4 mediated metabolism and P-glycoprotein efflux transport activity. C-DNA baculovirus expressed CYP3A4 and Caco-2 cells were used. Ketoconazole and verapamil were applied as positive control inhibitors, respectively. A validated high-performance liquid chromatography methodology was used to quantify the formation of 6-OH-testosterone and scintillation counting was used to quantify the transport of (3)H-digoxin. All the investigated herbs inhibited CYP3A4 activity. St. John's wort was the strongest inhibiting herb with an IC(50) value of 15.4 microg/ml, followed by common sage, Ginkgo biloba, common valerian, horse chestnut and Echinacea purpurea. All herbs also inhibited P-glycoprotein activity. Ginkgo biloba was the strongest inhibiting herb, inhibiting the net digoxin flux with an IC(50) value of 23.6 microg/ml, followed by St. John's wort, horse chestnut, common sage, common valerian and Echinacea purpurea. No correlation was found between the herbs inhibitory potentials towards CYP3A4 and P-glycoprotein activities. Ginkgo biloba, horse chestnut and common sage, besides St. John's wort, are suggested candidates for in vivo intestinal herb-drug pharmacokinetic interactions.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. bent.h.hellum@ntnu.no
authors.forename: Bent H
authors.initials: BH
authors.lastname: Hellum
authors.forename: Odd Georg
authors.initials: OG
authors.lastname: Nilsen
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004077:Digoxin / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D028321:Plant Preparations / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D065692:Cytochrome P-450 CYP3A Inhibitors; D010936:Plant Extracts; D028321:Plant Preparations; D013739:Testosterone; D004077:Digoxin; D014700:Verapamil; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D007654:Ketoconazole