| The possible beneficial effects of tea consumption have attracted a great deal of attention. Many of the biological effects have been attributed to tea catechins, including (−)-epigallocatechin (EGC), (−)-epicatechin (EC), (−)-epigallocatechin gallate (EGCG), and (−)-epicatechin gallate (ECG); however, the bioavailability and biotransformation of catechins is not clear. In the present study, various methylated and glucuronidated catechins were synthesized chemically or enzymatically. With newly developed analytical methods, methylated EGC, EC, and EGCG were detected in humans and animals after consumption of green tea or pure catechins. The pharmacokinetic properties of the major methylated catechin metabolites were characterized in human and animal samples along with their parent compounds. Both catechins and their methylated derivatives reached their peak values within the first 2 h following tea ingestion by human subjects. The maximum plasma concentration of 4′-O-methyl-(−)-epigallocatechin (4′-McEGC) was 4–6 times higher than that of EGC, whereas the plasma levels of methylated EC and EGCG were lower than that of EC and EGCG. Methylated catechins appeared to have longer half-lives than catechins. Glucuronidated and sulfated catechins in vivo were also investigated in the present study.; Three ring-fission metabolites, (−)-5-(3′,4 ′,5′-Trihydroxyphenyl)-γ-valerolactone (M4), (−)-5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (M6),and (−)-5–(3′,5′-dihydroxyphenyl)-γ-valerolactone (M6′), were detected in human urine after green tea ingestion. M4, M6′, and M6 were all observed after the ingestion of pure EGCG or EGC by human subjects, whereas only M6 was produced after EC ingestion. Methylated M4 and M6 were also detected in human urine since M4 and M6 preserved the catechol structures from catechins.; EGCG and 4″-O-methyl-(−)-epigallocatechin gallate (4″-McEGCG) exhibited strong activities in scavenging DPPH free radical. Methylated EGCG and EGC also showed stronger inhibitory activities than EGCG and EGC against the release of arachidonic acid from colon cancer line HT-29 at 1μM. Methylation of L-Dopa was observed to be inhibited by EGCG and methylated EGCG in vitro with IC 50 about 150 nM.; The identification and characterization of these metabolites in vivo will enhance our understanding of the possible health promotion effects of tea consumption. Because of the substantial amounts of these metabolites distributed in the body, it is interesting to investigate their possible biological activities. |
