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.