Abstract
1ScopeFlavonoids are generally studied in vitro, in isolation, and as unmetabolized precursor structures. However, in the habitual diet, multiple flavonoids are consumed together and found present in the circulation as complex mixtures of metabolites. Using a unique study design, we investigated the potential for singular or additive anti‐inflammatory effects of flavonoid metabolites relative to their precursor structures.2Methods and resultsSix flavonoids, 14 flavonoid metabolites, and 29 combinations of flavonoids and their metabolites (0.1–10 μM) were screened for their ability to reduce LPS‐induced tumor necrosis factor‐α (TNF‐α) secretion in THP‐1 monocytes. One micromolar peonidin‐3‐glucoside, cyanidin‐3‐glucoside, and the metabolites isovanillic acid (IVA), IVA‐glucuronide, vanillic acid‐glucuronide, protocatechuic acid‐3‐sulfate, and benzoic acid‐sulfate significantly reduced TNF‐α secretion when in isolation, while there was no effect on TNF‐α mRNA expression. Four combinations of metabolites that included 4‐hydroxybenzoic acid (4HBA) and/or protocatechuic acid also significantly reduced TNF‐α secretion to a greater extent than the precursors or metabolites alone. The effects on LPS‐induced IL‐1β and IL‐10 secretion and mRNA expression were also examined. 4HBA significantly reduced IL‐1β secretion but none of the flavonoids or metabolites significantly modified IL‐10 secretion.3ConclusionThis study provides novel evidence suggesting flavonoid bioactivity results from cumulative or additive effects of circulating metabolites.
Highlights
Flavonoids are phenolic secondary plant metabolites found ubiquitously in our habitual diets [1, 2]
To ensure that the effects of the treatments in the present study were not influenced by cell viability, THP-1 cells were treated with 5–100 M flavonoid for 24 h and cell viability was measured by WST-1 assay
Rather than concentrating on dietary flavonoids, the present study focused on the bioactivity of the more physiologically relevant flavonoid metabolites, as phenolic metabolites are reported to be the predominant compounds in the systemic circulation [17, 19, 32, 36]
Summary
Flavonoids are phenolic secondary plant metabolites found ubiquitously in our habitual diets [1, 2]. They have been extensively studied due to the widely held hypothesis that they. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com
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