Cytochrome P450 2C19 inhibitory activity of common berry constituents.
The cytochrome P450 enzyme CYP2C19 is involved in the metabolism of many commonly prescribed drugs, including proton pump inhibitors, antiepileptics and antidepressants. CYP2C19 inhibitors from food and food supplements may augment the toxicity of these agents and lead to noncompliance with treatment. The present investigation addresses CYP2C19 inhibition by 18 berry constituents using a chemiluminescent assay. Test compounds displayed inhibitory properties in a concentration-dependent fashion, with IC(50) values ranging from 20.2 microM up to >316 microM. In the order of decreasing effect size, anthocyanidins were followed by anthocyanidin-monoglycosides and procyanidins. Anthocyanidin-diglucosides exhibited weak and biphasic effects. When compared with the CYP2C19 inhibitor fluvoxamine, the flavonoids under study were 50- to 750-fold less potent. It is concluded that the above natural substances are moderate to poor inhibitors of CYP2C19 in vitro.
Sand
Philipp G
PG
University of Regensburg, Department of Psychiatry, Regensburg, Germany. philipp.sand@klinik.uni-regensburg.de
Dreiseitel
Andrea
A
Stang
Martin
M
Schreier
Peter
P
Oehme
Anett
A
Locher
Sanja
S
Hajak
Goeran
G
D000872:Anthocyanins / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D065731:Cytochrome P-450 CYP2C19; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016666:Fluvoxamine / Q000494:pharmacology; D018565:Food-Drug Interactions; D005638:Fruit / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008163:Luminescent Measurements; D044945:Proanthocyanidins / Q000494:pharmacology
D000872:Anthocyanins; D004791:Enzyme Inhibitors; D044945:Proanthocyanidins; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D016666:Fluvoxamine