Effect of flavonoids on cytochrome P450 activity in the gut – an in vitro food-drug interaction study

Abstract

Cytochrome P450 enzymes have a remarkable role in the xenobiotics metabolism. Oxidation of drugs and food components catalysed by the same isoenzyme can lead to drug-food interactions. Greatest quantity of CYP enzymes can be found in the liver. Nevertheless, the intestinal CYP garniture also contributes to the metabolism of clinically important drugs. Our research focused on the effects of flavonoids on the intestinal CYP enzymes. Intestinal epithelial cells (IPEC-J2) were treated by apigenin and apigenin-trimethylether. Phenobarbital was used as CYP inducer, mixture of naphtoflavone and ketoconazole as inhibitor. The CYP1A1, CYP1A2 and CYP3A activities were measured by chemiluminescent assay. Treatment of enterocytes with antipyrine was also performed in order to test possible drug interactions. Both flavones worked as significant CYP3A4 inhibitors. There was no significant difference between the inhibitory effects of the flavones at the same dose. However, apigenin-trimethylether combined with the inducer, was a more potent inhibitor, than the apigenin. Antipyrine decreased the enzymatic activity, which effect was enhanced, when antipyrine and apigenin were administered simultaneously. In conclusion, our results suggest that both apigenin and its trimethylated derivative can inhibit the intestinal CYP3A, which is the most important role in the metabolism of clinically relevant drugs.