Inhibitory effects of fruit juices on cytochrome P450 2C9 activity in vitro.
Hidaka M., Nagata M., Kawano Y., Sekiya H., Kai H., Yamasaki K., Okumura M., Arimori K.
Author Affiliation: School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshinocho, Nobeoka, Miyazaki 882-8508, Japan.
Bioscience, Biotechnology and Biochemistry 72 : 406-411
Abstract : The effects of fruit juice on CYP2C9-mediated drug metabolism were studied. Fruits of Citrus grandis [C. maxima], C. paradisi, C. depressa, C. tamurana, C. limon, C. aurantiifolia, C. reticulata, C. sinensis, Actinidia chinensis, Litchi chinensis, Mangifera indica, Garcinia mangostana, Cucumis melo, Carica papaya, Punica granatum and Ananas comosus were evaluated. The effects of the fruits on diclofenac 4?-hydroxylation and tolbutamide hydroxylation by human liver microsomes were investigated. Among the fruits, pineapple juice showed potent inhibition of CYP2C9 activity. The addition of 25 µlitre (5.0% v/v) pineapple juice resulted in almost complete inhibition. The inhibitory effect of bromelain, a cysteine protease [proteinase] in pineapple, was also studied. Bromelain markedly inhibited CYP2C9 activity. E-64, a cysteine protease inhibitor, almost entirely blocked inhibition by pineapple juice and bromelain. The results indicated that pineapple juice is a potent inhibitor of CYP2C9, and that the inhibitory effect might be due to bromelain in pineapple.