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.
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DOI：
10.1002/mnfr.201700053
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发表时间：
2017-09
影响因子：
5.2
通讯作者：
Kay CD
中科院分区：
文献类型：
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作者：
Warner EF;Smith MJ;Zhang Q;Raheem KS;O'Hagan D;O'Connell MA;Kay CD
当代细胞培养研究的生理相关性往往是令人困惑的，考虑到在超生理浓度下使用未代谢的植物化学物质。我们研究了生理相关花青素代谢物特征的活性，这些特征来自于先前在8名健康受试者中进行的500 mg 13 C5-花青素-3-葡萄糖苷的药代动力学研究，对人内皮细胞中可溶性血管粘附分子-1（VCAM-1）和白细胞介素-6（IL-6）的影响。使用纯标准品重现峰代谢物的特征（先前在推注后1、6和24 h鉴定），并在低于和高于观察到的平均血清水平（<5 μM）10倍的浓度下研究影响。所有处理均降低了肿瘤坏死因子-α（TNF-α）刺激的VCAM-1，在6和24 h曲线中观察到最大效应。在低于平均血清浓度10倍（0.19-0.44 μM）的浓度下检测的曲线仍保持活性。IL-6在1、6和24 h曲线中降低，在浓度高于2 μM时，在6 h和24 h曲线中观察到最大效应。VCAM-1和IL-6 mRNA的降低反映了蛋白反应，但对磷酸化NFκB-p65表达无影响。饮食消耗后花青素代谢物的特征减少VCAM-1和IL-6的产生，提供了生理相关生物活性的证据。
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. 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. Signatures of anthocyanin metabolites following dietary consumption reduce VCAM‐1 and IL‐6 production, providing evidence of physiologically relevant biological activity.