Objective: To observe the effects of kaempferol and quercetin on the activity of cytochrome P450 in rat hepatocytes.
Methods: Primarily cultured rat hepatocytes were exposed to kaempferol or quercetin in concentrations of 0.1, 1, 10 micromol/L for 12 h, 24 h and 48 h. Hepatocytes CYP isoemzymes-erythromycin N-demethylase (ERND) and aminopyrine N-demethylase (ADM) activities were determined by Nash methods. Erythromycin (10 micromol/L) was used as positive control and DMSO(0.1%) as solvent control.
Results: Kaempferol and quercetin inhibited ENRD activity in a dose-and time-dependent manner. In dose-response study, the ENRD activities in kaempferol (0.1,1 and 10 micromol/L) treated groups were (0.088+/-0.008), (0.074+/-0.006) and (0.041+/-0.003)micromol/(mg.min(-1)), respectively. ENRD activity in quercetin treated groups at the same concentrations were (0.082+/-0.007), (0.063+/-0.007) and (0.034+/-0.005) micromol/(mg.min(-1)), respectively. In time-courses study, the ENRD activity exposed to 10 micromol/L kaempferol or quercetin for 12 h and 48 h were (0.053+/-0.006) and (0.037+/-0.007) micromol/(mg.min(-1)), or (0.067+/-0.005) and (0.032+/-0.004) micromol/(mg.min(-1)). ADM activity was inhibited only by kaempferol in 10 mol/L at 24 h, but was not significantly altered by quercetin at any concentration tested.
Conclusion: In the present condition, kaempferol and quercetin act as potential CYP3A4 inhibitors as they can significantly inhibit ENRD in primarily cultured rat hepatocytes.