In vitro antioxidative activity of (-)-epicatechin glucuronide metabolites present in human and rat plasma.
Recently we identified four conjugated glucuronide metabolites of epicatechin, (-)-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) from plasma and urine. E3'G and 4'ME3'G were isolated from human urine, while E7G and 3'ME7G were isolated from rats that had received oral administration of (-)-epicatechin (Natsume et al. (2003), Free Radic. Biol. Med. 34,840-849). It has been suggested that these metabolites possess considerable in vivo activity, and therefore we carried out a study to compare the antioxidant activities of the metabolites with that of the parent compound. This was achieved by measuring superoxide scavenging activity, reduction of plasma TBARS production and reduced susceptibility of low-density-lipoprotein (LDL) to oxidation. (-)-Epicatechin was found to have more potent antioxidant activity than the conjugated glucuronide metabolites. Both (-)-epicatechin and E7G had marked antioxidative properties with respect to superoxide radical scavenging activity, plasma oxidation induced by 2,2'-azobis-(2-aminopropane) dihydrochloride (AAPH) and LDL oxidation induced by copper ions or 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN). In contrast, the other metabolites had light antioxidative activities over the range of physiological concentrations found in plasma.
Natsume
Midori
M
Healthcare R&D Laboratories, Meiji Seika Kaisha Ltd, Sakado-shi, Saitama 350-0289, Japan. midori_natsume@meiji.co.jp
Osakabe
Naomi
N
Yasuda
Akiko
A
Baba
Seigo
S
Tokunaga
Takashi
T
Kondo
Kazuo
K
Osawa
Toshihiko
T
Terao
Junji
J
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001391:Azo Compounds / Q000037:antagonists & inhibitors; D002392:Catechin / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D005965:Glucuronates / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000037:antagonists & inhibitors; D016877:Oxidants / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D013481:Superoxides / Q000737:chemistry; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry
D000975:Antioxidants; D001391:Azo Compounds; D016166:Free Radical Scavengers; D005965:Glucuronates; D008077:Lipoproteins, LDL; D009570:Nitriles; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; C480662:epicatechin-3'-O-glucuronide; D013481:Superoxides; C109522:V 70; D002392:Catechin