Impact of food polyphenols on oxylipin biosynthesis in human neutrophils.
Biochimica et biophysica acta. Molecular and cell biology of lipids(2019)
摘要
The intake of food polyphenols is associated with beneficial impacts on health. Besides anti-oxidative effects, anti-inflammatory properties have been suggested as molecular modes of action, which may result from modulations of the arachidonic acid (AA) cascade. Here, we investigated the effects of a library of food polyphenols on 5-lipoxygenase (5-LOX) activity in a cell-free assay, and in human neutrophils. Resveratrol, its dimer (ε-viniferin), and its imine analogue (IRA) potently blocked the 5-LOX-mediated LT formation in neutrophils with IC50 values in low μM-range. Among the tested flavonoids only the isoflavone genistein showed potent 5-LOX inhibition in neutrophils (IC50 = 0.4 ± 0.1 μM), however was ineffective on isolated 5-LOX. We exclude an interference with the 5-LOX-activating protein (FLAP) in HEK_5-LOX/±FLAP cells and suggest global effects on intact immune cells. Using LC-MS based targeted oxylipin metabolomics, we analyzed the effects of 5-LOX-inhibiting polyphenols on all branches of the AA cascade in Ca2+-ionophore-challenged neutrophils. While ε-viniferin causes a clear substrate shunt towards the remaining AA cascade enzymes (15-LOX, cyclooxygenase - COX-1/2, cytochrome P450), resveratrol inhibited the COX-1/2 pathway and showed a weak attenuation of 12/15-LOX activity. IRA had no impact on 15-LOX activity, but elevated the formation of COX-derived prostaglandins, having no inhibitory effects on COX-1/2. Overall, we show that food polyphenols have the ability to block 5-LOX activity and the oxylipin pattern is modulated with a remarkable compound/structural specificity. Taken the importance of polyphenols for a healthy diet and their concentration in food supplements into account, this finding justifies further investigation.
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关键词
Polyphenols,Inflammation,Arachidonic acid cascade,5-Lipoxygenase,Oxylipin pattern
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