Inhibitory effects of conjugated epicatechin metabolites on peroxynitrite-mediated nitrotyrosine formation

Previously, we identified four metabolites of (-)-epicatechin in blood and urine: (-)-epicatechin-3′-O-glucuronide (E3′G), 4′-O-methyl-(- )-epicatechin-3′-O-glucuronide (4′ME3′G), (-)-epicatechin-7-O- glucuronide (E7G), and 3′-O-methyl-(-)-epicatechin-7-O-glucuronide (3′ME7G) (Natsume et al. Free Radical Biol. Med. 34, 840-849, 2003). The aim of the current study was to compare the antioxidative activities of these metabolites with that of their parent compound. After oral administration of (-)-epicatechin, E3′G and 4′ME3′G were isolated from human urine, and E7G and 3′ME7G isolated from rat urine. We found that these compounds inhibited peroxynitrite-mediated tyrosine nitration, in the following order of potency: E3′G > (-)-epicatechin > E7G = 3′ME7G. = 4′ME3′G. These results demonstrate that the metabolites of (-)-epicatechin retain antioxidative activity on peroxynitrite-induced oxidative damages to some extent.