Luo, Z, Morgan, MRA and Day, AJ (2015) Transport of trans-tiliroside (kaempferol-3-β-D-(6’’-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestine. Xenobiotica: the fate of foreign compounds in biological systems. ISSN 0049-8254
Abstract
1.Absorption and metabolism of tiliroside (kaempferol 3-β-D-(6’’-p-coumaroyl)-glucopyranoside) and its related compounds kaempferol, kaempferol-3-glucoside and p-coumaric acid were investigated in the small intestinal Caco-2 cell model. Apparent permeation (Papp) was determined as 0.62 10-6 cm/s, 3.1 10-6 cm/s, 0 and 22.8 10-6 cm/s respectively. 2. Mechanistic study showed that the transportation of tiliroside, kaempferol-3-glucoside and p-coumaric acid in Caco-2 model were transporter(s) involved, while transportation of kaempferol was solely by passive diffusion mechanism. 3. Efflux transporters, multi-drug-resistance-associated protein-2 (MRP2), was shown to play a role in limiting the uptake of tiliroside. Inhibitors of MRP2, (MK571 and rifampicin) and co-incubation with kaempferol (10 μM), increased transfer from the apical to the basolateral side by three-five fold. 4. Metabolites of kaempferol-3-glucoside and p-coumaric acid were not detected in the current Caco-2 model, while tiliroside was metabolised to a limited extent, with two tiliroside mono-glucuronides identified; and kaempferol was metabolised to a higher extent, with three mono-glucuronides and two mono-sulfates identified. 5. In conclusion, tiliroside was metabolised and transported across Caco-2 cell membrane to a limited extent. Transportation could be increased by applying MRP2 inhibitors or co-incubation with kaempferol. It is proposed that tiliroside can be absorbed by human; future pharmacokinetics studies are warranted in order to determine the usefulness of tiliroside as a bioactive agent.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015, Informa Healthcare . This is an author produced version of a paper published in Xenobiotica. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Flavonoid; Coumaroyl-glucoside; Efflux transporters; MRP2; Bioavailability; Flavonol ester |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 May 2015 13:47 |
Last Modified: | 12 Apr 2016 06:18 |
Published Version: | http://dx.doi.org/10.3109/00498254.2015.1007492 |
Status: | Published |
Publisher: | Informa Healthcare |
Refereed: | Yes |
Identification Number: | 10.3109/00498254.2015.1007492 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:84299 |