PMID- 28457017 OWN - NLM STAT- MEDLINE DCOM- 20180723 LR - 20231112 IS - 1613-4133 (Electronic) IS - 1613-4125 (Print) IS - 1613-4125 (Linking) VI - 61 IP - 9 DP - 2017 Sep TI - Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells. LID - 10.1002/mnfr.201700053 [doi] LID - 1700053 AB - 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 (13) C(5) -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 muM) serum levels. Tumor necrosis factor-alpha (TNF-alpha)-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 muM) 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 muM. Protein responses were reflected by reductions in VCAM-1 and IL-6 mRNA, however there was no effect on phosphorylated NFkappaB-p65 expression. CONCLUSION: Signatures of anthocyanin metabolites following dietary consumption reduce VCAM-1 and IL-6 production, providing evidence of physiologically relevant biological activity. CI - (c) 2017 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Warner, Emily F AU - Warner EF AD - Department of Nutrition, Norwich Medical School, Bob Champion Research and Education Building, University of East Anglia, Norwich, UK. AD - School of Pharmacy, University of East Anglia, Norwich, UK. FAU - Smith, Michael J AU - Smith MJ AD - Department of Nutrition, Norwich Medical School, Bob Champion Research and Education Building, University of East Anglia, Norwich, UK. AD - School of Biological Sciences, University of East Anglia, Norwich, UK. FAU - Zhang, Qingzhi AU - Zhang Q AD - School of Chemistry, University of St. Andrews, Fife, Scotland, UK. FAU - Raheem, K Saki AU - Raheem KS AD - School of Chemistry, University of St. Andrews, Fife, Scotland, UK. AD - Department of Life Sciences, Faculty of Science and Technology, University of Westminster, London, UK. FAU - O'Hagan, David AU - O'Hagan D AD - School of Chemistry, University of St. Andrews, Fife, Scotland, UK. FAU - O'Connell, Maria A AU - O'Connell MA AD - School of Pharmacy, University of East Anglia, Norwich, UK. FAU - Kay, Colin D AU - Kay CD AD - Department of Nutrition, Norwich Medical School, Bob Champion Research and Education Building, University of East Anglia, Norwich, UK. AD - Food Bioprocessing & Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, USA. LA - eng GR - BB/H004726/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/H004963/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BB/H00503X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article DEP - 20170609 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Anthocyanins) RN - 0 (Biomarkers) RN - 0 (Glucosides) RN - 0 (Interleukin-6) RN - 0 (Transcription Factor RelA) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 0 (cyanidin-3-O-beta-glucopyranoside) SB - IM MH - Anthocyanins/*metabolism/pharmacology MH - Biomarkers MH - Cells, Cultured MH - Endothelial Cells/*drug effects MH - Glucosides/*pharmacology MH - Humans MH - Interleukin-6/analysis/*antagonists & inhibitors/genetics MH - Transcription Factor RelA/metabolism MH - Tumor Necrosis Factor-alpha/pharmacology MH - Vascular Cell Adhesion Molecule-1/analysis/*antagonists & inhibitors/genetics PMC - PMC5600085 OTO - NOTNLM OT - Adhesion OT - Anthocyanin OT - Inflammation OT - Metabolism EDAT- 2017/05/01 06:00 MHDA- 2018/07/24 06:00 PMCR- 2017/09/15 CRDT- 2017/05/01 06:00 PHST- 2017/01/15 00:00 [received] PHST- 2017/03/15 00:00 [revised] PHST- 2017/04/11 00:00 [accepted] PHST- 2017/05/01 06:00 [pubmed] PHST- 2018/07/24 06:00 [medline] PHST- 2017/05/01 06:00 [entrez] PHST- 2017/09/15 00:00 [pmc-release] AID - MNFR2920 [pii] AID - 10.1002/mnfr.201700053 [doi] PST - ppublish SO - Mol Nutr Food Res. 2017 Sep;61(9):1700053. doi: 10.1002/mnfr.201700053. Epub 2017 Jun 9.