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

• Main Authors: Sarah C. Forester, Joshua D. Lambert
• Format: Article
• Language: English
• Published: Elsevier 2015-08-01
• Series: Journal of Functional Foods
• Subjects: Bioavailability; Catechol-O-methyltransferase; (-)-epigallocatechin-3-gallate; Green tea; Tolcapone
• Online Access: http://www.sciencedirect.com/science/article/pii/S1756464615002509

(-)-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.