Effects of Herbal Extracts on the Function of Human Organic Anion-Transporting Polypeptide Oatp-B

Abstract

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 aniontransporting 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 g/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.

Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1

“…A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 21 Our data are in line with a previous publication showing that Ginkgo leaf extracts and quercetin-3-glucoside, quercetin-3-rutinoside, kaempferol-3-glucoside, and kaempferol-3-rutinoside inhibited the OATP2B1-mediated transport of estrone-3-sulfate in HEK293-cells stably expressing OATP2B1 [18].…”

“…However, it is not stated whether fexofenadine (120 mg) and Ginkgo biloba extract (120 mg) were given simultaneously. Therefore, it could be speculated that the lack of significance is caused by a non simultaneous administration of Ginkgo biloba extract and fexofenadine.Page 21 of 37A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 21 Our data are in line with a previous publication showing that Ginkgo leaf extracts and quercetin-3-glucoside, quercetin-3-rutinoside, kaempferol-3-glucoside, and kaempferol-3-rutinoside inhibited the OATP2B1-mediated transport of estrone-3-sulfate in HEK293-cells stably expressing OATP2B1 [18].In the present study we also established HEK293 cells stably expressing OATP1A2. In previous studies investigating the function of OATP1A2, Xenopus laevis oocytes or Hela cells transiently expressing OATP1A2 were used [10][11].…”

“…These results suggest that coadministration of some dietary supplements may decrease the absorption of orally administered OATP2B1 substrates [18].…”

“…Because we previously found that fexofenadine is not a substrate of OATP2B1 [9] only the impact of flavonoids on the OATP1A2-mediated uptake of fexofenadine was investigated. Apigenin was the most potent inhibitor of OATP1A2-mediated fexofenadine transport with the lowest IC 50 value followed by kaempferol and 18 …”

Identification of natural products as modulators of OATP2B1 using LC-MS/MS to quantify OATP-mediated uptake

“…In vivo studies showed that grapefruit, orange, and apple juices greatly reduced the plasma concentration of aliskiren, probably by inhibiting its OATP2B1-mediated influx in the small intestine (Tapaninen et al, 2010(Tapaninen et al, , 2011. Fuchikami et al (2006) showed that some herbal extracts used in dietary supplements significantly inhibited the function of OATP2B1, suggesting that co-administration of some dietary supplements might decrease the absorption of orally administered substrates of OATP2B1. Roth et al (2011) reported that green tea catechins epicatechin gallate and epigallocatechin gallate significantly inhibited OATP2B1-mediated E3S uptake.…”