Abstract:
Flavonoids are metabolized in vivo to monocyclic
phenolic acids. We investigated whether 18 phenolic acids of the benzoic,
phenylacetic, phenylpropanoic or cinnamic series - known or potential
metabolites of flavonoids - inhibit reactive oxygen species (ROS) released
by human polymorphonuclear neutrophils (PMNs). Chemiluminescence was measured
after PMN stimulation with three agents (N-fMetLeuPhe, phorbol myristate acetate
(PMA), or opsonised zymosan) using two probes (lucigenin or luminol) with
or without horseradish peroxidase (HRP) in order to derive specificity profiles
for each test compound. The profiles of the phenolic acids and flavonoids
were compared by a multivariate (correspondence) factor analysis. Overall,
the phenolic acids were less specific than the flavonoids and, with a few
exceptions, less potent. Phenolic acids had virtually no effect on the chemiluminescence
related to O2·- formation that is measured
by lucigenin but inhibited luminol luminescence. Inhibition for all but two
phenolic acids was sensitive to HRP and might be explained by a scavenger
mechanism. Few structure-activity relationships emerged suggesting that simple
properties such as radical scavenging and/or redox activity rather than overall
structure might be the key determinants of chemiluminescence inhibition. Whatever
the mechanism, however, we conclude that part of the
in vivo pharmacological activity of flavonoids may readily be accounted
for by phenolic acids.
Key words:
Flavonoids - phenolic acids - chemiluminescence - reactive oxygen species - free radical
scavengers - correspondence analysis
