Modulation of human cytochrome P450 1A1 expression by flavones and flavonols-structural requirements

摘要

To elucidate the structural features governing flavonoids interactions with CYP1A1, fifteen kinds of flavones and flavonols were selected. Human CYP1A1 expresssion by flavones and flavonols in the absence and presence of DMBA were examined by a quantitative real-time reverse transcription polymerase chain reaction in HepG2 cells. Eight flavonoids including flavone, 6-hydroxyflavone, quercetin, baicalin, baicalein, scutellarein, scutellarin and chrysin significantly increased CYP1A1 expression, whereas apigenin, 7-hydroxyflavone and fisetin markedly decreased CYP1A1 expression at 25 or 50 μmol/L. Otherwise, flavone, 6-hydroxyflavone, quercetin, chrysin, 7-hydroxyflavone and apigenin inhibited DMBA-induced CYP1A1 expression at 1 or 10 μmol/L, in contrast to the increase of DMBA-induced CYP1A1 expression by baicalein and scutellsrein. Structure analyse shows that 3, 5, 6-hydroxylation of the flavone nucleus has potent CYP1Al-inducing effects. Aglycones show a much stronger inducing effect on CYP1A1 expression than the corresponding glycosides. But no significant flavonoid structure-CYP1Al level relationship is found on DMBA-induced CYP1A1 expression.