The catechol-O-methyltransferase inhibitor, tolcapone, increases the bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice. (August 2015)

• Record Type: Journal Article
• Authors: Forester, Sarah C.; Lambert, Joshua D.
• Is Part Of: Journal of functional foods. Volume 17(2015)
• Page Start: 183
• Page End: 188
• Publication Date: 2015-08
• Subjects: AUC area under the curve -- CI confidence interval -- COMT catechol-O-methyltransferase -- DiMeEGCG 4′, 4″-di-O-methyl-(-)-epigallocatechin-3-gallate -- EGCG (-)-epigallocatechin-3-gallate -- GTP green tea polyphenol -- i.g intragastric -- LC–MS liquid chromatography–mass spectrometry -- MeEGCG 4″-O-methyl-(-)-epigallocatechin-3-gallate -- OR odds ratio -- TOL tolcapone; Bioavailability -- Catechol-O-methyltransferase -- (-)-epigallocatechin-3-gallate -- Green tea -- Tolcapone; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2015.05.012
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: Epigallocatechin gallate (EGCG) is methylated by catechol methyltransferase (COMT). We report the effect of tolcapone, a COMT inhibitor, on unmetabolized EGCG in mice Tolcapone increased fraction of unmethylated EGCG in plasma and tissue samples. Abstract: (-)-Epigallocatechin-3-gallate (EGCG), has been shown to inhibit cancer in vivo . EGCG, however, is rapidly methylated by catechol- O -methyl transferase (COMT), which reduces its cancer preventive efficacy. Tolcapone (TOL) is a clinically-used COMT inhibitor. Here, we examined the effect of TOL on the bioavailability of EGCG in male CF-1 mice. Plasma and tissue levels of EGCG and its methyl metabolites were determined following intragastric administration of EGCG (100 mg/kg), TOL (30 mg/kg), or the combination. In mice treated with EGCG, unmethylated plasma EGCG accounted for 63.4% of the total. Co-administration of TOL increased this fraction to 87.9%. In the urine, unmethylated EGCG accounted for 29.2% of the total, whereas treatment with EGCG plus TOL increased this to 81.8%. Similar effects were observed in the major organs examined. TOL effectively inhibited the methylation of EGCG in vivo . Future studies should examine the cancer preventive effects of the combination.