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

Abstract

ScopeThe 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 resultsSignatures 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.ConclusionSignatures of anthocyanin metabolites following dietary consumption reduce VCAM‐1 and IL‐6 production, providing evidence of physiologically relevant biological activity.

Phytochemicals and Traditional Use of Two Southernmost Chilean Berry Fruits: Murta (Ugni molinae Turcz) and Calafate (Berberis buxifolia Lam.)

“…Although all catabolites were found in concentration peaks between 0.1 and 1 mu M, no parental anthocyanins were detected [95]. Currently, it is postulated that anthocyanin bioactivity in vivo results from lesser studied, though more bioavailable, phenolic metabolites [96,97] and some authors have demonstrated that these phenolic metabolites are more active on inflammatory biomarkers than their precursor structures (parent anthocyanins) [97,98]. In this sense, the bioactivity of anthocyanin metabolites in murta and calafate must continue to be studied in order to achieve adequate information on the biological activity and health-promoting effects derived for the consumption of murta and calafate fruit.…”

The Bioavailability, Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective

“…The colonic flavan‐3‐ol catabolite 5‐(3′,4′‐dihydroxyphenyl)‐γ‐valerolactone 30 has been shown to inhibit nitrite production and iNOS in macrophage models. Phenolic catabolites of anthocyanins have also been reported to act on TNF‐α, VCAM‐1, ICAM‐1, IL‐6, and MCP‐1 (Amin et al., ; Rodriguez‐Mateos et al., ; Warner et al., , ;). Flavonoid catabolites from the serum of mice fed blueberries was also shown to inhibit TNF‐α and IL‐6, by reducing phosphorylation of MAPK, JNK, p38, and ERK1/2 in macrophage cell lines (Rodriguez‐Mateos et al., ).…”

“…In addition, Warner et al. () investigated the activity of 1, 6, and 24 hr postprandial metabolite signatures of cyanidin‐3‐ O ‐glucoside 63 in stimulated endothelial cells. Here both IL‐6 and VCAM‐1 were significantly reduced in response to all mixtures/signatures tested.…”

“…Here both IL‐6 and VCAM‐1 were significantly reduced in response to all mixtures/signatures tested. Interestingly, activity was observed at concentrations 10‐fold lower than those occurring in plasma after ingestion of the precursor anthocyanin (Warner et al., ).…”

Polyphenol Phase‐II Metabolites are Detectable in Human Plasma after Ingestion of 13C Labeled Spinach—a Pilot Intervention Trial in Young Healthy Adults

“…Bacterial degradation of polyphenols can form a great variety of metabolites showing functional properties in the lumen or (after absorption) in tissue cells such as short chain fatty acids. Recent studies are focusing on colonic‐derived metabolites and several small molecular weight compounds, like 4‐hydroxyphenylacetic acid, protocatechuic acid, 4‐hydroxybenzoic acid, caffeic acid, or 3,5‐dihydroxyphenylpropionic acid were identified through fecal in vitro fermentation …”