3 years ago

Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells

Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells
David O'Hagan, Michael J. Smith, Maria A. O'Connell, Emily F. Warner, Colin D. Kay, Qingzhi Zhang, K. Saki Raheem
Scope The physiological relevance of contemporary cell culture studies is often perplexing, given the use of unmetabolized phytochemicals at supraphysiological concentrations. We investigated the activity of physiologically relevant anthocyanin metabolite signatures, derived from a previous pharmacokinetics study of 500 mg 13C5-cyanidin-3-glucoside in eight healthy participants, on soluble vascular adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) in human endothelial cells. Methods and results Signatures of peak metabolites (previously identified at 1, 6, and 24 h post-bolus) were reproduced using pure standards and effects were investigated across concentrations ten-fold lower and higher than observed mean (<5 μM) serum levels. Tumor necrosis factor-α (TNF-α)-stimulated VCAM-1 was reduced in response to all treatments, with maximal effects observed for the 6 and 24 h profiles. Profiles tested at ten-fold below mean serum concentrations (0.19–0.44 μM) remained active. IL-6 was reduced in response to 1, 6, and 24 h profiles, with maximal effects observed for 6 h and 24 h profiles at concentrations above 2 μM. Protein responses were reflected by reductions in VCAM-1 and IL-6 mRNA, however there was no effect on phosphorylated NFκB-p65 expression. Conclusion Signatures of anthocyanin metabolites following dietary consumption reduce VCAM-1 and IL-6 production, providing evidence of physiologically relevant biological activity. A novel approach to exploring the biological activity of flavonoid metabolitesin vitro. We investigated the activity of anthocyanin metabolite signatures, identified in a previous pharmacokinetic study of 13C5-cyanidin-3-glucoside. Here, differing concentrations of metabolite signatures inhibited soluble vascular adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) in human endothelial cells, providing evidence of physiologically relevant biological activity of anthocyanin metabolites.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mnfr.201700053

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