Effects of Polyphenols on Vasomodulatory Factors and Associated Cell Signalling

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.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2013

Author dc:creator

• Woodcock, Mark

Language dc:language

en