Abstract
Polyphenols are plant secondary metabolites which possess many positive effects on
human health. Although these beneficial effects could be mediated through an increase
in nitric oxide synthase activity, little is known regarding the inhibitory effect
of polyphenols on mammal arginase, an enzyme which competes with nitric oxide synthase
for their common substrate, L-arginine. The aim of the present study was to determine
the potential of a series of polyphenols as mammalian arginase inhibitors and to identify
some structure-activity relationships. For this purpose, we first developed a simple
and cost-effective in vitro colorimetric microplate method using commercially-available mammal bovine liver arginase
(b-ARG 1). Among the ten tested polyphenolic compounds [chlorogenic acid, piceatannol,
resveratrol, (−)-epicatechin, taxifolin, quercetin, fisetin, caffeic acid, quinic
acid, and kaempferol], cholorogenic acid and piceatannol exhibited the highest inhibitory
activities (IC50 = 10.6 and 12.1 µM, respectively) but were however less active as (S)-(2-Boronoethyl)-L-cysteine (IC50 = 3.3 µM), used as reference compound. Enzyme kinetic studies showed that both chlorogenic
acid and piceatannol are competitive arginase inhibitors. Structural data identified
the importance of the caffeoyl (3,4-dihydroxycinnamoyl)-part and of the catechol function
in the inhibitory activity of the tested compounds. These results identified chlorogenic
acid and piceatannol as two potential core structures for the design of new arginase
inhibitors.
Key words
phenolic compounds - arginase inhibitors -
in vitro microplate assay
