Bioscience Biotechnology and Biochemistry · 2008 · 34 citations · 19 references
MedicineBiochemistryPharmacologyBiochemical PharmacologyDrug MetabolismMetabolismCytochrome P450 EnzymesCytochrome P450-mediated MetabolismDrug-metabolizing EnzymesEnzyme InhibitionFruit BiochemistryHepatic Drug MetabolismCitrus FruitsCysteine Protease MechanismCytochrome P450 2C9Cytochrome P450 Enzyme ActivityCytochrome P450 Enzyme InhibitionCytochrome P450 Human Liver MicrosomesCytochrome P450 InhibitionFruit Juice Consumption
There is limited information on the effect of fruits on human cytochrome P450 (CYP) 2C9 activity. The objective of this study was to determine the effect of fruit juice on CYP2C9-mediated drug metabolism. Nine citrus fruits and eight tropical fruits were chosen. We investigated effects of the fruits on diclofenac 4'-hydroxylation and tolbutamide hydroxylation by human liver microsomes. Among the fruits, pineapple juice showed potent inhibition of CYP2C9 activity. The addition of 25 microl (5.0% v/v) of pineapple juice resulted in almost complete inhibition. Next we examined the inhibitory effect of bromelain, a cysteine protease in pineapple. Bromelain also strongly inhibited CYP2C9 activity. In addition, E-64, a cysteine protease inhibitor, almost entirely blocked inhibition by pineapple juice and bromelain. Thus we found that pineapple juice was a potent inhibitor of CYP2C9, and that the inhibitory effect might be due to the bromelain contained in pineapple.
19
Thorir D. Bjornsson, John T. Callaghan, Heidi J. Einolf et al. · Drug Metabolism and Disposition · 2003 · 784 citations
The cysteine proteinases of the pineapple plant.
Andrew D. Rowan, David J. Buttle, A. John Barrett · PubMed · 1990 · 212 citations