Unique uptake and transport of isoflavone aglycones by human intestinal caco-2 cells: comparison of isoflavonoids and flavonoids.
Soy isoflavonoids have attracted much attention because of their estrogenic activity. To study the intestinal absorption of the isoflavonoids, we investigated the cellular uptake and metabolism of genistein and daidzein and their glucosides, genistin and daidzin, by Caco-2 cell monolayers as a model of the human intestinal epithelium. When Caco-2 monolayers were incubated with genistein or daidzein at 10 micromol/L from the apical (mucosal) side, aglycone was lost from the apical solution for 2.0 h (P < 0.05) and the glucuronide/sulfates appeared at the level of 1-2 micromol/L. In the basolateral (serosal) solution, both intact aglycones and their glucuronide/sulfates increased (P < 0.05) with time and reached approximately 20 and 15% of the initial dose, respectively. The transport of their glucosides, genistin and daidzin, through Caco-2 monolayers was less than one tenth that of the aglycones. The cellular metabolism of genistein was compared with quercetin, kaempferol, luteolin and apigenin. Only genistein aglycone was transported intact to the basolateral solution. Transport was greater (P < 0.05) than that of flavonoid aglycones and was without an appreciable decrease of transepithelial resistance. Radical scavenging activity was not related to the susceptibility to conjugation of flavonoids/isoflavonoids. Affinity to the liposomal membrane was increased in the order of genistin = daidzin < daidzein < genistein << flavonoid aglycones. These results strongly suggest that isoflavone aglycones are taken up into enterocytes more efficiently than their glucosides because of their moderate lipophilicity. Furthermore, they are generally transported to the basolateral side in intact form in contrast to flavonoids, probably due to their unique isoflavonoid structure.
Murota
Kaeko
K
Department of Nutrition, School of Medicine, The University of Tokushima, 3-18-15, Kuramoto-cho, Japan.
Shimizu
Sumie
S
Miyamoto
Sayuri
S
Izumi
Toru
T
Obata
Akio
A
Kikuchi
Mamoru
M
Terao
Junji
J
D001667:Binding, Competitive; D018938:Caco-2 Cells / Q000737:chemistry / Q000502:physiology; D002457:Cell Extracts / Q000737:chemistry; D017097:Electric Impedance; D005419:Flavonoids / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D019833:Genistein / Q000493:pharmacokinetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007529:Isoflavones / Q000493:pharmacokinetics* / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism
D002457:Cell Extracts; D005419:Flavonoids; D016166:Free Radical Scavengers; D007529:Isoflavones; D008081:Liposomes; C040641:genistin; C013908:daidzin; C004742:daidzein; D019833:Genistein