title: In vitro inhibition of cytochrome P450 3A4 by Aronia melanocarpa constituents.
abstract: Extracts, subfractions, isolated anthocyanins and procyanidins, and two phenolic acids from aronia [Aronia melanocarpa] were investigated for their CYP3A4 inhibitory effects, using midazolam as the probe substrate and recombinant insect cell microsomes expressing CYP3A4 as the enzyme source. Procyanidin B5 was a considerably stronger CYP3A4 inhibitor in vitro than the isomeric procyanidin B2 and comparable to bergamottin, a known CYP3A4 inhibitor from grapefruit juice. The inhibitory activity of proanthocyanidin-containing fractions was correlated to the degree of polymerization. Among the anthocyanins, cyanidin 3-arabinoside showed stronger CYP3A4 inhibition than cyanidin 3-galactoside and cyanidin 3-glucoside. Thus, the ability to inhibit CYP3A4 in vitro seems to be influenced by the sugar unit linked to the anthocyanidin.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, Blindern, Oslo, Norway. p.m.braunlich@farmasi.uio.no
authors.forename: Marie
authors.initials: M
authors.lastname: Bräunlich
authors.forename: Hege
authors.initials: H
authors.lastname: Christensen
authors.forename: Siri
authors.initials: S
authors.lastname: Johannesen
authors.forename: Rune
authors.initials: R
authors.lastname: Slimestad
authors.forename: Helle
authors.initials: H
authors.lastname: Wangensteen
authors.forename: Karl E
authors.initials: KE
authors.lastname: Malterud
authors.forename: Hilde
authors.initials: H
authors.lastname: Barsett
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044946:Biflavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002392:Catechin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D005638:Fruit / Q000737:chemistry; D011564:Furocoumarins / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007313:Insecta; D008861:Microsomes; D008874:Midazolam / Q000378:metabolism; D046936:Photinia / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D044945:Proanthocyanidins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000872:Anthocyanins; D044946:Biflavonoids; D065692:Cytochrome P-450 CYP3A Inhibitors; D011564:Furocoumarins; D062385:Hydroxybenzoates; D010936:Plant Extracts; D044945:Proanthocyanidins; D002392:Catechin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C017616:phenolic acid; C068337:bergamottin; D008874:Midazolam; C479582:procyanidin B5