Burmese grape, common lime, pomelo, salak, Southern langsat, star fruit, and orange modulate the expression of cytochrome P450 enzymes in mouse livers

Abstract

Cytochrome P450 isoenzymes (CYPs) is responsible for xenobiotic and drug metabolism, and highly expressed in liver. Diet and daily dietary supplements might modify the expression of CYPs, leading to the undesirable side-effects of drugs. The effects of eight Thai sour fruits, namely Burmese grape (Baccaurea ramiflora Lour.), common lime (Citrus aurantifolia Linn.), pomelo (Citrus maxima (Burm) Merrill), salak (Salacca zalacca (Gaertn.) Voss), Southern langsat (Lansium domesticum Corr.), special honey orange (Lonicera japonica Thunb.), star fruit (Averrhoa carambola Linn.), and Thanathon orange (Citrus sinensis Osb.), on the expression of hepatic CYPs were determined. Effects of the aqueous extract of all fruits (0.8 to 25 mg/mL) on the CYPs enzyme activities were determined in vitro using the reactions established enzymatic assays (EROD, MROD, BROD/PROD, and ENDM). The fruit, which possessed the most potent inhibitory activity, was selected to determine its effect in vivo on the expression and activities of CYPs in mouse livers. All eight Thai sour fruits were found to inhibit the activities of Cyp1a1, Cyp1a2, Cyp2b9/10, and Cyp3a via inhibition of EROD (IC50 = 0.001 – 25.91 mg/mL), MROD (IC50 = 0.681 – 84.95mg/mL), BROD (IC50 = 0.221 – 52.28 mg/ mL), PROD (IC50 = 0.111 – 64.51 mg/mL), and ENDM (IC50 = 34.27 – 59.62 mg/mL) reactions, respectively. Burmese grape exhibited the most potent inhibitory activity and inhibited the largest number of CYPs. Burmese grape was therefore selected for further in vivo study, the fruit juice being tested at a dose of 250, 500, and 1,000 mg/kg/day for 7 and 28 days. The highest dose of Burmese grape (1,000 mg/kg/day) induced Cyp1a1, Cyp1a2, and Cyp2b9/10 activities. However, Cyp3a11 activity was significantly inhibited by Burmese grape treatments. Hence, Thai sour fruit consumption, especially Burmese grape, may induce food-drug interactions, particularly if they are consumed for a long time and in large quantities. *Correspondence to: Waranya Chatuphonprasert, Faculty of Medicine, Mahasarakham University, Mahasarakham, Thailand, Tel: +66-43-722-393; E-mail: waranya.c@msu.ac.th