Effects of Polyphenols on Vasomodulatory Factors and Associated Cell Signalling

Woodcock, Mark (2013) Effects of Polyphenols on Vasomodulatory Factors and Associated Cell Signalling. Doctoral thesis, University of East Anglia.

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There is increasing evidence that consumption of plant bioactives such as polyphenols
reduces cardiovascular disease risk and improves endothelial function. In the Black Sea
area, a number of plants are consumed alone and as ingredients in traditional foods, and
dill, nettle, kale, Sideritis, pomegranate and persimmon were identified as polyphenolrich
traditional food plants. Bioactive-rich extracts of their edible parts were used to treat
human umbilical vein endothelial cells (HUVECs), to assess effects on the abundance or
activity of signalling molecules related to increased vasodilation, a hallmark of improved
endothelial function. Specifically, Akt and eNOS phosphorylation, levels of total eNOS
protein and cGMP, secretion of ET-1 and levels of nitrate/nitrite in cell culture media
were assayed. Alongside these experiments, HUVECs were treated with quercetin, a
flavonol found in a number of the plant extracts, alongside a mix of its human
metabolites to assess their effect on a broad range of phosphorylated proteins using an
antibody microarray.
Quercetin (50 μM) significantly decreased eNOS phosphorylation (p < 0.05),
while extracts of pomegranate and persimmon significantly increased levels of
phosphorylated (p-) Akt, p-eNOS and cell culture media nitrate/nitrite (p < 0.05), and
significantly reduced secretion of the vasoconstrictor ET-1 (p < 0.001). With regards to
pomegranate bioactivity, signalling events upstream of p-Akt were explored, including
inhibition of PTEN activity and phosphorylation of receptor tyrosine kinases, though no
evidence could be found that either mechanism was involved in this case. Fractionation
of the pomegranate extract into its main polyphenol classes revealed that procyanidins
were responsible for its bioactivity. These findings suggest that procyanidin-rich foods
can improve markers of endothelial function in vitro. Further studies on procyanidin
bioavailability are required to determine if these effects can also occur in vivo.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Users 2259 not found.
Date Deposited: 12 Jun 2014 13:39
Last Modified: 12 Jun 2014 13:39
URI: https://ueaeprints.uea.ac.uk/id/eprint/48760


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