Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17 beta-estradiol.
Naringenin, quercetin and kaempferol, which may be found in glycoside form in natural compounds such as grapefruit, are potent inhibitors of cytochrome P-450 metabolism. The influence of these flavonoids on the metabolism of 17 beta-estradiol was investigated in a microsome preparation from human liver. The flavonoids were added in concentrations of 10, 50, 100, 250 and 500 mumol/l to the microsome preparation. The metabolism of 17 beta-estradiol was concentration dependently inhibited by all the flavonoids tested. Addition of the flavonoids to the microsome preparation did not influence estrone formation, while a potent inhibition of estriol formation was observed. At the highest concentrations tested of the respective flavonoid, there was approximately 75-85% inhibition of estriol formation. However, naringenin was a less potent inhibitor of 17 beta-estradiol metabolism as compared to quercetin and kaempferol. The most likely mechanism of action of the flavonoids on 17 beta-estradiol metabolism is inhibition of the cytochrome P-450 IIIA4 enzyme, which catalyzes the reversible hydroxylation of 17 beta-estradiol into estrone and further into estriol. These hydroxylation processes represent the predominant steps of the hepatic metabolic conversion of endogenous as well as exogenous 17 beta-estradiol. This interaction would be expected to inhibit the first-pass metabolism of 17 beta-estradiol, and this has recently been demonstrated after oral administration of 17 beta-estradiol to women.
Schubert
W
W
Department of Obstetrics & Gynaecology, Sahlgren's University Hospital, Gothenburg, Sweden.
Eriksson
U
U
Edgar
B
B
Cullberg
G
G
Hedner
T
T
D000328:Adult; D001628:Beverages; D002957:Citrus; D004958:Estradiol / Q000378:metabolism*; D004964:Estriol / Q000037:antagonists & inhibitors / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004970:Estrone / Q000037:antagonists & inhibitors / Q000378:metabolism; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D018565:Food-Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D044949:Kaempferols; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008875:Middle Aged; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004965:Estrogen Antagonists; D044950:Flavanones; D005419:Flavonoids; D044949:Kaempferols; D004970:Estrone; D004958:Estradiol; C006552:kaempferol; D011794:Quercetin; D004964:Estriol; C005273:naringenin