[Effects of kaempferol and quercetin on cytochrome 450 activities in primarily cultured rat hepatocytes].
To observe the effects of kaempferol and quercetin on the activity of cytochrome P450 in rat hepatocytes.



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.



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.



In the present condition, kaempferol and quercetin act as potential CYP3A4 inhibitors as they can significantly inhibit ENRD in primarily cultured rat hepatocytes.
Institute of Medical Nutrition and Food Hygiene, Zhejiang University, Hangzhou 310031, China.
Fang-fang
FF
Zhang
Yi-fan
YF
Zheng
Hui-juan
HJ
Zhu
Xiao-yun
XY
Shen
Xin-qiang
XQ
Zhu
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000378:metabolism; D044949:Kaempferols / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D044949:Kaempferols; C006552:kaempferol; D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin; D051544:Cytochrome P-450 CYP3A; D000633:Aminopyrine N-Demethylase