The presented findings indicate that the vascular benefits of blueberry anthocyanins are mediated by their metabolites. Blueberries might complement existing therapies to lessen vascular complications.

The vascular benefits of anthocyanins might be mediated by their circulating metabolites. This mechanism has not been explored because the metabolites are not commercially available. We synthesized the blueberry (BB) metabolites vanillic acid‐4‐sulfate (V4S), isovanillic acid‐3‐sulfate (IV3S) and benzoic acid‐4‐sulfate (B4S) and verified their purity (>98 %) using HPLC‐mass spectrometry. We tested the hypothesis that a mixture of these BB‐metabolites attenuates endothelial inflammation induced by lipotoxicity. Human aortic endothelial cells (HAEC) were treated ± BB‐metabolite mixture for 6 h and ± 500 μM palmitate for the last 5 h. The BB‐metabolite mixture contained V4S, IV3S, B4S, hydroxyhippuric acid, and hippuric acid at concentrations reported to peak in the blood 4 ‐ 6 h after consuming 240 g of blueberries in humans. Cell adhesion (assessed via human monocytic THP‐1 cells), and mRNA expression of ICAM‐1, VCAM‐1, E‐selectin, MCP1, IL‐8, NFκB‐p65, IKKβ, IKBα (assessed via qPCR), were quantified ± palmitate ± BB‐metabolites. Palmitate‐treatment increased (p<0.05) cell adhesion and increased (p<0.05) mRNA expression of ICAM‐1, VCAM‐1, E‐selectin, MCP‐1, IL‐8, and IKBα without affecting cell viability. All these effects were ameliorated (p<0.05) by BB‐metabolites. BB‐metabolites, at physiologically relevant concentrations suppressed lipotoxicity induced endothelial inflammation, which may be mediated via NFκB pathway. Blueberries might complement existing therapies to improve vascular complications.