Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665967
Title: The vascular and anti-inflammatory activity of cyanidin-3-glucoside and its metabolites in human vascular endothelial cells
Author: Amin, Hiren
ISNI:       0000 0004 5352 5548
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2015
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Abstract:
High dietary consumption of anthocyanins has been associated with a reduced risk of cardiovascular disease (CVD), which is supported by evidence from human, animal and in vitro studies. However, owing to anthocyanins’ poor bioavailability and extensive metabolism, it is likely their metabolites are responsible for their reported health effects; yet the bioactivity of anthocyanin metabolites remains largely unknown. This thesis aimed to address this deficiency in current scientific literature by investigating the vascular and anti-inflammatory activity of cyanidin-3-glucoside (C3G), the most abundant anthocyanin in the UK diet, and 11 of its recently identified metabolites (including six synthetic metabolites) at physiological concentrations (0.1 – 10 µM) in a human endothelial cell model. Here protein and mRNA levels were established using ELISA and RT-qPCR, superoxide levels were quantified by spectrophotometric measure of cytochrome creduction and electron paramagnetic resonancespectroscopy, and nuclear factor kappa B (NF-κB) activation was established by flow cytometry. The data indicate that C3G, its A-ring degradant, phloroglucinaldehyde (PGA), and its phase II metabolite vanillic acid (VA) increased the basal expression of endothelial nitric oxide synthase (eNOS) by between 1.5- to-3 fold (p<0.05). In contrast, none of the compounds tested modulated angiotensin II (Ang II)-stimulated superoxide production and basal endothelin-1 expression in endothelial cells. Anti-inflammatory activity of the treatments was characterised by their effects upon oxidised low density lipoprotein (oxLDL) and cluster of differentiation 40 ligand (CD40L) stimulated expression of vascular cell adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) in endothelial cells. Here, significant bioactivity of C3G metabolites was observed, as 7 out of 12 of the tested treatments reduced CD40L-induced VCAM-1 expression up to 65% (relative to control, p<0.05), eight compounds reduced CD40L-induced IL-6 production up to 95% (relative to control, p<0.05), and nine compounds reduced oxLDL-induced IL-6 protein secretion up to 99% of control incubations (p<0.05). Protocatechuic acid (PCA) and VA reduced VCAM-1 and IL-6 protein and mRNA levels under both stimulation conditions, and were therefore selected for further targeted investigation of transcription factor activity. Here IL-1β-induced activation of nuclear factor-kappa B (NF-κB) was significantly reduced by both PCA and VA (p<0.05). Therefore, anthocyanin metabolites appear to exert their effects on inflammatory chemokines through attenuation of NF-κB p65 phosphorylation in endothelial cells. In summary, the beneficial effects of anthocyanins in Page 3 vivo may arise, in part, from the anti-inflammatory activity of their metabolites, as the metabolites displayed significant anti-inflammatory activity and are found in the circulation at considerably higher concentrations than their unmetabolised precursor structures, hence likely contributing to the observed vascular activity in humans. These findings provide novel insight to bioactivity of anthocyanins and extend current knowledge in the field of anthocyanin research.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.665967  DOI: Not available
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