title: Comparative evaluation of 12 immature citrus fruit extracts for the inhibition of cytochrome P450 isoform activities.
abstract: In a previous study we found that 50% ethanol extracts of immature fruits of Citrus unshiu (satsuma mandarin) have anti-allergic effects against the Type I, II and IV allergic reactions. However, many adverse interactions between citrus fruit, especially grapefruit juice, and drugs have been reported due to the inhibition of cytochrome P450 (CYP) activities. The purpose of this study was to examine the competitive inhibitory effects of extracts from immature citrus fruit on CYP activity. Extracts were prepared from 12 citrus species or cultivars, and were tested against three kinds of major CYPs, CYP2C9, CYP2D6 and CYP3A4, in human liver microsomes. We also estimated the amounts of flavonoids (narirutin, hesperidin, naringin and neohesperidin) and furanocoumarins (bergapten, 6',7'-dihydroxybergamottin and bergamottin) in each extract using HPLC. Citrus paradisi (grapefruit) showed the greatest inhibition of CYP activities, while Citrus unshiu which has an antiallergic effect, showed relatively weak inhibitory effects. Extracts having relatively strong inhibitory effects for CYP3A4 tended to contain higher amounts of naringin, bergamottin and 6',7'-dihydroxybergamottin. These results, providing comparative information on the inhibitory effects of citrus extracts on CYP isoforms, suggest that citrus extracts containing high levels of narirutin and hesperidin and lower levels of furanocoumarins such as C. unshiu are favorable as antiallergic functional ingredients.
authors.affiliation: School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Fujita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawase
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niwa
authors.forename: Norimichi
authors.initials: N
authors.lastname: Tomohiro
authors.forename: Megumi
authors.initials: M
authors.lastname: Masuda
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwaki
mesh_terms: D018926:Anti-Allergic Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002957:Citrus / Q000737:chemistry*; D003374:Coumarins / Q000032:analysis / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008862:Microsomes, Liver / Q000201:enzymology; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D018926:Anti-Allergic Agents; D003374:Coumarins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D010936:Plant Extracts