Effect of Betong Watercress and Phenethyl Isothiocyanate on N-Demethylation of Caffeine in Rats

Purpose: To investigate the effect of Betong watercress and phenethyl isothiocyanate (PEITC) on the N-demethylation of caffeine (CF) in rats
Methods: Male Wistar rats were subjected to 2 phases of experiment. Phase I, they received a single oral dose of CF (10 mg/kg), while in phase II, they were pretreated with the following regimens: 10 mg/kg fluvoxamine, i.p.; a single oral dose of 2, 10, and 20 mg/kg PEITC; 2, 10, and 20 mg/kg PEITC, once daily for five days; single oral dose of 800 mg/kg Betong watercress; 800 mg/kg Betong watercress once daily for five days, before receiving the same dose of CF as in phase I. Serum concentrations of CF and its metabolites after 3 h of CF administration were measured. Caffeine metabolic ratios (CMRs) and ratio of serum concentration of metabolites to that of CF were calculated and compared.
Results: CMRs were decreased by a single pretreatment \with fluvoxamine (30 – 40%), PEITC (2 - 20 mg/kg) (40 – 55%), and Betong watercress (9 – 22%). The decreases caused by 10 and 20 mg/kg PEITC were significantly greater than those by fluvoxamine. CMRs were also decreased after five days of pretreatment with all doses of PEITC (43 – 69%) and Betong watercress (28 – 44%). The reduction in metabolic ratio after single- and multiple PEITC pretreatments was dose- and time-independent.
Conclusion: Betong watercress and PEITC inhibit N-demethylation of CF in rats. Such an effect indicates that they have inhibitory activity on CYP1A2 and CYP2C.

Keywords
Watercress; Phenethyl isothiocyanate; Caffeine; N-demethylation; Fluvoxamine; Cytochrome