Anthocyanins and anthocyanidins are poor inhibitors of CYP2D6

Abstract

BackgroundThe cytochrome P450 CYP2D6 isoform is involved in the metabolism of about 50% of all psychoactive drugs, including neuroleptic agents, selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Therefore, inhibition of cytochrome P450 by foodstuffs has implications for drug safety. The present study addresses inhibitory effects of polyphenolic anthocyanins and their aglycons that are found in many dietary fruits and vegetables. Methods Following incubation of membrane preparations containing recombinant human CYP2D6enzyme with anthocyanins and their aglycons, inhibition of enzyme activity was determined using a chemiluminescent assay. ResultsBoth anthocyanins and their aglycons, the anthocyanidins, inhibited CYP2D6 activity in a concentration-dependent manner with IC 50 values ranging from 55 µM, for the anthocyanidin pelargonidin, to over 800 µM for diglycoside anthocyanins pelargonin and cyanin. ConclusionsAccording to earlier data on furanocoumarins from grapefruit extract, CYP2D6 inhibition is achieved in the range of 190 to 900 nM. In comparison, the tested anthocyanins and anthocyanidins were shown to be about 1000-fold less potent, and unlikely to interfere with drug metabolism by CYP2D6. However, further studies are invited to examine effects of the above flavonoids on other CYP isoforms for more detailed toxicity profiles.