title: Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B.
abstract: Most known interactions between herbal extracts and drugs involve the inhibition of drug-metabolizing enzymes, but little is yet known about the possible role of transporters in these interactions. In this study, we have examined the effects of herbal extracts used in dietary supplements on the function of organic anion-transporting polypeptide B (OATP-B; OATP2B1), which is expressed on human intestinal epithelial cells and is considered to be involved in the intestinal absorption of various drugs. Specifically, the effects of 15 herbal extracts on uptake of estrone-3-sulfate, a typical OATP-B substrate, by human embryonic kidney 293 cells stably expressing OATP-B were evaluated. At concentration levels considered likely to be attainable in the human intestine, extracts of bilberry, echinacea, green tea, banaba, grape seed, ginkgo, and soybean potently inhibited estrone-3-sulfate uptake by 75.5, 55.5, 82.1, 61.1, 64.5, 85.4, and 66.8%, respectively (P < 0.01). The inhibitory effect of ginkgo leaf extract was concentration-dependent (IC(50) = 11.2 +/- 3.3 microg/ml) and reversible. Moreover, flavonol glycosides and catechins significantly inhibited the function of OATP-B, suggesting that the inhibitory effects of the herbal extracts on OATP-B may be primarily attributable to flavonoids. The extracts of mulberry, black cohosh, and Siberian ginseng moderately (but significantly) inhibited estrone-3-sulfate uptake by 39.1, 47.2, and 49.2%, respectively (P < 0.05). Extracts of barley, Job's tears, rutin, rafuma, and passionflower were ineffective. These results suggest that coadministration of some dietary supplements may decrease the absorption of orally administered substrates of OATP-B.
authors.affiliation: Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fuchikami
authors.forename: Hiroki
authors.initials: H
authors.lastname: Satoh
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Ohdo
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ohtani
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sawada
mesh_terms: D028241:Camellia sinensis; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D044948:Flavonols / Q000494:pharmacology; D020441:Ginkgo biloba; D005905:Glyburide / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology; D006801:Humans; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D013662:Tea; D014162:Transfection
chemical_list: D044948:Flavonols; D006027:Glycosides; D027361:Organic Anion Transporters; D010936:Plant Extracts; C450859:SLCO2B1 protein, human; D013662:Tea; D004970:Estrone; D002392:Catechin; C017296:estrone sulfate; D005905:Glyburide