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Title: Uptake and metabolism of tiliroside in model systems
Author: Luo, Zijun
ISNI:       0000 0004 2719 2487
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2011
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Tiliroside (kaempferol 3-P-D-(6"-p-coumaroyl)-glucopyranoside) is a flavonol ester present in a number of herbal plants and present at a low level in a number of foods. Increasing evidence from in vitro and in vivo animal studies shows tiliroside may have health beneficial effects in humans, such as anti-inflammatory and hepatoprotective action, however high concentrations were used in these studies. Of prime importance is an understanding oftiliroside bioavailability, however, tiliroside absorption and metabolism has never been studied. Results from experiments with Caco-2 cells showed that tiliroside was passively transferred across the intestinal model. Only 1 % was transferred although a significant efflux, proposed to be by MRP2, was observed. Efflux inhibition by application of MRP2 inhibitors to the Caco-2 media significantly increased uptake of tiliroside; eo-incubation with kaempferoI also increased tiliroside transfer four- fold. The apparent permeability coefficient (P app) for tiliroside, in the absence of inhibitors, was 0.62 x 10-6 cm/s which would predict absorption of tiliroside in humans. Based on in vitro enzyme studies and the Caco-2 model, tiliroside can be directly glucuronidated, although activity appears to be low. At least two mono-glucuronide conjugates of tiliroside were tentatively identified based on LC-MS/MS. Esterase activity was detected from saliva and liver extracts, but not from human intestinal extracts or Caco-2 cells. Thus, if absorbed intact, some tiliroside is likely to be hydrolysed to kaempferol-3-0-glucoside in the liver. Further studies are required to determine the extent of absorption and metabolic pathways in humans. The interactions of tiliroside and other flavonoids with aqueous and oil systems were studied. Water-insoluble tiliroside (Log P = 2.7), and some other flavonoids such as rutin and naringin, can adsorb to the oil-water (O/W) interface and act as a Pickering emulsion stabiliser. This is the first time such emulsifying activity has been observed for flavonoids. The mechanism of this activity was studied further; in particular the effect of pH was examined with the mean emulsion droplet size being considerably smaller at higher pH. A pilot study on the interaction of tiliroside with a bile salts- stabilised emulsion was also performed and evidence suggests that tiliroside was able to adsorb to the O/W interface along with the bile salts. These particle- stabilising effects may have significant implications on the delivery and absorption of flavonoids, as well as on the digestion and absorption of fat and fat related components. Furthermore, there is potential for flavonoids to be used by the food industry to create stable, long shelf-life, food emulsions. Future studies should focus on the pharmacokinetics of tiliroside in humans to determine the maximum plasma concentration, metabolic and excretion pathways. Tiliroside is likely to be absorbed intact and a proportion may be present unmodified. The bioactivity of the physiological concentrations should be considered.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available