title: 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.
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), were 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 to 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.
authors.affiliation: Campden BRI, Food Manufacturing Technologies , Chipping Campden , UK and.
authors.forename: Zijun
authors.initials: Z
authors.lastname: Luo
authors.forename: Michael R A
authors.initials: MR
authors.lastname: Morgan
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Day
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells / Q000378:metabolism; D003373:Coumaric Acids / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D044949:Kaempferols / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D011422:Propionates; D013997:Time Factors
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003373:Coumaric Acids; D005419:Flavonoids; D044949:Kaempferols; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011422:Propionates; C052083:tiliroside; C006552:kaempferol; C495469:p-coumaric acid
keywords: Bioavailability; MRP2; coumaroyl-glucoside; efflux transporters; flavonoid; flavonol ester