Premium
The bioactivity of flavonoids is likely the result of cumulative low exposure to a variety of structurally similar phenolic metabolites
Author(s) -
Kay Colin,
Gesso Jessica,
Warner Emily,
Amin Hiren,
Ferrars Rachel,
Edwards Michael,
Zang Qing,
O'Hagan David,
O'Connell Maria
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.118.4
Subject(s) - metabolite , chemistry , nitric oxide , inflammation , biochemistry , pharmacology , monocyte , biology , immunology , organic chemistry
Activities of 21 flavonoid metabolites were investigated relative to their unmetabolized structures, utilizing 20 assays of vascular reactivity, inflammation and cellular adhesion, in endothelial (HUVEC), smooth muscle (AVSMC) and monocyte (THP‐1) cells, at physiologically relevant concentrations (0.1‐10µM). Unmetabolized flavonoids were generally less active than their phenolic metabolites. In vascular screens no metabolites altered expression of endothelin‐1 or nitric oxide, 3 metabolites induced eNOS, 2metabolites reduced angiotensin‐II induced superoxide, no metabolites induced NOX or p47phox, 1 metabolite upregulated p22phox and 3 metabolites induced HO‐1. In vascular inflammation and adhesion screens in HUVEC, 10, 9 and 6 metabolites reduced IL‐6 following CD40L, oxLDL or TNF‐α stimulation, respectively. 10 and 6 metabolites reduced sVCAM‐1 following CD40L or TNF‐α stimulation, respectively. 2 metabolites attenuated IL‐1β‐stimulated phosphorylation of NF‐κB p65, 1 metabolite induced Nrf2. In monocyte activity assays, 5 metabolites reduced LPS‐induced TNF‐α, 1 metabolite induced IL1B, no metabolites were active on HO‐1, tissue factor, NFkB or nfKB. The evidence suggests that bioactivity of flavonoids in vivo results from low exposure to a variety of structurally similar metabolites modifying inflammation and cellular adhesion pathways. Support: UK Biotechnology and Biological Sciences Research Council (BB/I006028/1, BB/H004963/1).