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Title: Unravelling the anti-diabetic effects of polyphenols in chamomile : the gastrointestinal tract as a potential site of action
Author: Villa Rodriguez, Jose Alberto
ISNI:       0000 0004 6494 6620
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2017
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Background and objective: Polyphenol-rich foods and extracts have been proposed of being capable of lower imbalance in energy metabolism and type 2 diabetes risk by mitigating postprandial glycaemia. However, this physiological action is still controversial due to conflicting in vivo evidence which is partially due to their limited characterisation in terms of active constituents, their targets and efficacies. This study systematically investigated the potential of a polyphenol rich-extract (chamomile) to blunt postprandial sugar rise, the compounds involved and biochemical pathways affected. Methods: A combination of HPLC and LC/QTOF were used to characterise the polyphenol profile of aqueous chamomile extract. The inhibition of carbohydrate-digesting enzymes was determined using an isolated human salivary α-amylase and acetone rat intestinal powder under optimal kinetic conditions. The inhibition of sugar transporters and cholesterol uptake was assessed in the well-characterised intestinal cell models Caco-2/TC7 and Caco-2 respectively. Results: When assessed by inhibition of α-amylase and maltase activities, the active components were apigenin-7-O-glucoside, apigenin, and (Z) and (E)-2-hydroxy-4-methoxycinnamic acid glucosides. The latter two compounds were purified and characterised. Molecular docking studies showed that apigenin and cinnamic acids present totally different poses in the active site of α-amylase which determined their potency. In differentiated Caco-2/TC7 cell monolayers, apigenin-7-O-glucoside and apigenin strongly inhibited D-[U-14C]-glucose and D-[U-14C]-sucrose transport, and less effectively D-[U-14C]-fructose transport, whereas the cinnamic acids were ineffective on all sugar transport. Inhibition of D-[U-14C]-glucose transport by apigenin was stronger under Na+-depleted conditions, suggesting interaction with the GLUT2 transporter and competitive binding studies with molecular probes indicate interaction primarily at the exofacial-binding site. The attenuation of glucose absorption had a knock on effect on [4-14C]-cholesterol uptake by downregulating Niemann-Pick C1 Like 1 protein. Conclusion: Chamomile extract containing apigenin and apigenin 7-O-glucoside or the individual components thereof, could potentially reduce glucose absorption and availability within the enterocyte attenuating the glucose and cholesterol-rich chylomicron particles during the postprandial phase.
Supervisor: Williamson, Gary Sponsor: CONACYT
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available