Complement fixing activity and in vitro inhibition of cytochrome P450 3A4 by Aronia melanocarpa constituents

M Bräunlich; H Christensen; S Johannesen; G Ho; H Wangensteen; H Barsett

doi:10.1055/s-0033-1352310

Planta Medica, Inhaltsverzeichnis

Complement fixing activity and in vitro inhibition of cytochrome P450 3A4 by Aronia melanocarpa constituents

M Bräunlich ¹, H Christensen ², S Johannesen ², G Ho ¹, H Wangensteen ¹, H Barsett ¹

¹University of Oslo, School of Pharmacy, Department of Pharmaceutical Chemistry, Blindern, 0316 Oslo, Norway
²University of Oslo, School of Pharmacy, Department of Pharmaceutical Biosciences, Blindern, 0316 Oslo, Norway

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.

Also, the extracts, subfractions, isolated anthocyanins and procyanidins together with isolated pectic polysaccharide fractions were analysed for complement fixing activity. Most of the polyphenols showed higher complement fixing activity than the polysaccharide fractions. Among the anthocyanins, cyanidin 3-glucoside possessed the highest activity, and of the isolated procyanidins B2, B5 and C1, the C1 showed the strongest and B2 the weakest complement fixing activity.