| Summary: | Anthocyanins, the class of flavonoid responsible for giving a red hue to many berries, have been associated with a decreased risk of cardiovascular disease. However, numerous intervention studies feeding anthocyanin-rich foods report limited (<1%) bioavailability of the parent anthocyanins in vivo. Due to the instability of anthocyanins at neutral pH, it is postulated that degradation products and metabolites of anthocyanins may be responsible for the perceived bioactive effects. The aims of the present thesis were: (1) To model and establish analytical methods for the extraction and quantification of putative anthocyanin metabolites in urine, serum and faecal samples. (2) To identify and explore the pharmacokinetics of anthocyanin metabolites via the analysis of urine, serum and faecal samples from two human interventions, feeding either (a) 500 mg of isotopically (13C5) labelled anthocyanin or (b) 500 mg elderberry anthocyanins for 12 wks. (3) To explore the impact of acute (500 mg) versus chronic (500 mg/day for 12 wks) anthocyanin consumption on their metabolism and (4) To investigate the anti-inflammatory activity of six anthocyanin metabolites at physiologically relevant concentrations (0.01 μM to 10 μM) using human umbilical vein endothelial cells (HUVECs). Following the consumption of 500 mg elderberry anthocyanins, 28 anthocyanin metabolites were identified in urine and 21 in plasma, with the phenolic metabolites within plasma identified at 45 fold higher levels than their parent compounds. Similar results were observed within the 13C-labelled anthocyanin intervention, where 17 13C-labelled compounds were identified in serum and 31 in urine. However, chronic consumption of anthocyanins had no impact on the formation of the metabolites. The cardiovascular bioactivity of anthocyanins may be linked to the antiinflammatory activity of their metabolites. IL-6 and VCAM-1 are cytokines and adhesion molecules integral to the initiation and progression of inflammation. In vitro, anthocyanin metabolites reduced CD40L and TNF-α stimulated expression of the inflammatory markers, sVCAM-1 and IL-6, indicating that the anti-inflammatory effects of anthocyanins are likely attributed to their metabolites. In conclusion, the present thesis provides a new understanding into the metabolism and bioactivity of anthocyanins, which should provide an informative insight into how the consumption of higher intakes of anthocyanins may contribute to optimising human health.
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