title: Modulation of CYP1A1 activity by a Ginkgo biloba extract in the human intestinal Caco-2 cells.
abstract: Ginkgo biloba is a widely consumed dietary supplement. Some dietary active compounds modulate the activity of biotransformation enzymes inside the enterocytes and more interestingly of cytochrome P-450 1A1 (CYP1A1). This enzyme is of a particular interest because of its implication in the metabolism of some exogenous pro-carcinogens or endogenous molecules. In the present work, we have used Caco-2 cells to study the effect of a standard reference material of a Ginkgo biloba extract (GBE) (10-400 μg/ml), as well as of its major individual active compounds (kaempferol, quercetin, isorhamnetin, ginkgolides and bilobalide), alone or in mixtures, at realistic intestinal concentrations, on the induction of CYP1A1 activity, in the presence or absence of benzo[a]pyrene (B[a]P) (0.1 μg/ml), a well-known CYP1A1 inducer. 3-O-rutinosides of kaempferol, quercetin and isorhamnetin were also tested. We have demonstrated a strong induction (p < 0.005) of CYP1A1 activity and a slight, but significant (p < 0.005), decrease of this activity in the presence of B[a]P by the GBE at the realistic exposure level of 100 μg/ml. The inductive effect was explained, in part, by quercetin and kaempferol after 24h exposure while unknown compounds seem to be responsible for the strong CYP1A1 induction observed after 6h exposure. The inhibitory potency of flavonols on CYP1A1 activity in presence of B[a]P was much stronger for the aglycones than for the 3-O-rutinosides, explaining the slight effect observed with the GBE, mainly composed of glycosylated flavonoids. These results indicate that GBEs may disturb intestinal CYP1A1 activity and, in turn, affect the metabolism of other compounds. The present paper thus highlights the necessity to take these side effects into account when administrating Ginkgo biloba herbal supplements.
authors.affiliation: Institut des Sciences de la Vie, Université catholique de Louvain, Croix du Sud 2/8 and 5/3, B-1348 Louvain-la-Neuve, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Ribonnet
authors.forename: A
authors.initials: A
authors.lastname: Callebaut
authors.forename: I
authors.initials: I
authors.lastname: Nobels
authors.forename: M-L
authors.initials: ML
authors.lastname: Scippo
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Schneider
authors.forename: S
authors.initials: S
authors.lastname: De Saeger
authors.forename: L
authors.initials: L
authors.lastname: Pussemier
authors.forename: Y
authors.initials: Y
authors.lastname: Larondelle
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D018938:Caco-2 Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004790:Enzyme Induction; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D019363:Cytochrome P-450 CYP1A1