Inhibitory effects of fruit juices on cytochrome P450 2C9 activity in vitro

• Published in: Bioscience, biotechnology, and biochemistry Vol. 72; no. 2; pp. 406 - 411
• Main Authors: Hidaka, M.(Kyushu Univ. of Health and Welfare, Nobeoka, Miyazaki (Japan)), Nagata, M, Kawano, Y, Sekiya, H, Kai, H, Yamasaki, K, Okumura, M, Arimori, K
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Society for Bioscience, Biotechnology, and Agrochemistry 01.02.2008; Japan Society for Bioscience Biotechnology and Agrochemistry; Oxford University Press
• Subjects: ANANAS (FRUITS); Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors; Aryl Hydrocarbon Hydroxylases - metabolism; Beverages; Biological and medical sciences; bromelain; Bromelains - pharmacology; CITOCROMO P450; COUMAFENE; Cytochrome P-450 CYP2C9; CYTOCHROME P450; cytochrome P450 2C9 (CYP2C9); DRUGS; Fruit; FRUIT JUICES; Fundamental and applied biological sciences. Psychology; JUGO DE FRUTAS; JUS DE FRUITS; MEDICAMENT; MEDICAMENTOS; METABOLISM; METABOLISME; METABOLISMO; Microsomes, Liver - enzymology; PINA; pineapple; PINEAPPLES; PROTEASAS; PROTEASE; Protease Inhibitors - pharmacology; PROTEASES; Ultrafiltration; WARFARIN; WARFARINA; pineapple; Cytochrome P450; Bromelains; cytochrome P450 2C9 (CYP2C9); Inhibition; Fruit juice; Biological activity; bromelain
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.70511

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 micro l (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.