植物成分apigeninの動物肝ミクロゾームによる代謝(自然科学編)

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Species and sex differences in the in vitro metabolism of apigenin (5,7,4'-trihydroxyflavone), a flavonoid abundant in plants, were examined using liver microsomes of rats, guinea pigs and hamsters and effect of two cytochrome P450 (P450) inducers, phenobarbital (PB) and 3-methylcholanthrene (MC), on apigenin metabolism was also examined. When incubated with animal liver microsomes and NADPH for 20 min at 37℃, apigenin was mainly oxidized to give a metabolite (M-1) in all species used in this study. M-1 was determined to be 3'-hydroxy-apigenin (luteolin) by a complete agreement of chromatographic behavior in HPLC. In untreated microsomes, the order of the activity to form luteolin was guinea pigs ≫ rats > hamsters. A significant sex difference in luteolin formation was observed in rats and hamsters. Especially, male rat liver microsomes produced luteolin at 6 times faster rate than female ones. PB-treatment did not almost affect the apigenin metabolism, whereas MC-treatment accelerated the metabolism in all species. Immunoinhibition study using antisera against rat CYP1A1 and hamster CYP1A2 revealed an involvement of both P450 enzymes in apigenin metabolism. These results suggest that the 3'-hydroxylation of apigenin to luteolin is catalyzed by MC-inducible P450 enzymes (CYP1A1 and CYP1A2) and a male-specific P450 (CYP2C11).
中村学園大学の論文