title: Transport mechanisms for soy isoflavones and microbial metabolites dihydrogenistein and dihydrodaidzein across monolayers and membranes.
abstract: Isoflavone data concerning the metabolism and permeability on intestinal epithelial cells are scarce, particularly for microbial isoflavone metabolites. This study evaluates the absorption mechanisms for the isoflavones, genistein and daidzein, and their microbial metabolites, dihydrogenistein (DHG) and dihydrodaidzein (DHD). The permeability characteristics of isoflavones were compared by using the Caco-2 human colon adenocarcinoma cell line for a parallel artificial membrane permeability assay, and comparing their physicochemical properties. The data suggest that genistein, DHG and DHD were efficiently transported by passive diffusion according to the pH-partition hypothesis. Genistein was conjugated by phase II metabolizing enzymes and acted as a substrate of the breast cancer resistance protein (BCRP). Daidzein was not conjugated but did act as a substrate for BCRP, multidrug resistance-associated proteins, and P-glycoprotein. In contrast, DHG and DHD were markedly more permeable than their parent isoflavones; they were therefore difficult to transport by the efflux effect, and glucuronidation/sulfation was limited by the flux time.
authors.affiliation: Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Miki
authors.initials: M
authors.lastname: Shinohara
authors.forename: Toshitada
authors.initials: T
authors.lastname: Nagai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D001692:Biological Transport; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004058:Diffusion; D019833:Genistein / Q000031:analogs & derivatives / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007529:Isoflavones / Q000378:metabolism*; D007700:Kinetics; D008567:Membranes, Artificial; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D013025:Glycine max / Q000737:chemistry; D013463:Sulfuric Acid Esters / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D019833:Genistein; D020719:Glucuronides; D007529:Isoflavones; D008567:Membranes, Artificial; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D013463:Sulfuric Acid Esters; C116614:ABCG2 protein, human; C433163:dihydrodaidzein; C004742:daidzein