Identification and characterization of methylated and ring-fission metabolites of tea catechins formed in humans, mice, and rats

被引:205
作者
Meng, XF
Sang, SM
Zhu, NQ
Lu, H
Sheng, SQ
Lee, MJ
Ho, CT
Yang, CS
机构
[1] Rutgers State Univ, Coll Pharm, Canc Res Lab, Piscataway, NJ 08854 USA
[2] Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA
[3] Rutgers State Univ, Dept Food Sci, Piscataway, NJ 08901 USA
关键词
D O I
10.1021/tx010184a
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
(-)-Epigallocatechin gallate (EGCG), the most abundant tea catechin, has been proposed to be beneficial to human health based on its strong antioxidative and other biological activities in vitro. Inadequate knowledge regarding the bioavailability and biotransformation of EGCG in humans, however, has limited our understanding of its possible beneficial health effects. In this study, 4',4"-di-O-methyl-EGCG (4',4"-DiMeEGCG) was detected in human plasma and urine by LC/MS/MS following green tea ingestion. Both 4',4"-DiMeEGCG and EGCG reached peak plasma values (20.5 +/- 7.7 and 145.4 +/- 31.6 nM, respectively, in 4 subjects) at 2 h after the dose. The half-lives of 4',4"-DiMeEGCG and EGCG were 4.1 +/- 0.8 and 2.7 +/- 0.9 h, respectively. The cumulative urinary excretion of 4',4"-DiMeEGCG during a 24 h period was 140.3 +/- 48.6,mug, about 5-fold higher than that of EGCG, but the excreted 4',4"-DiMeEGCG and EGCG in urine only accounted for about 0.1% of ingested EG-CG. (-)-5-(3',4',5'-Trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), along with another possible ring-fission metabolite, (-)-5-(3',5'-dihydroxyphenyl)-gamma-valerolactone (M6'), were detected in human urine after green tea ingestion. The cumulative excretion of M4, M6', and M6 during a 24 h period ranged from 75,mug to 1.2 mg, 0.6 to 6 mg, and 0.6 to 10 mg, respectively. The combined excretion of all three ring-fission metabolites accounted for 1.5-16% of ingested catechins. 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. These metabolites as well as monomethylated EGCG were detected in mice and rats after tea or EGCG administration, and the tissue levels reflected the rather low bioavailability of EGCG in rats. The presently characterized methylated EGCG metabolites and ring-fission products exist in substantial quantities and may contribute to the biological activities of tea.
引用
收藏
页码:1042 / 1050
页数:9
相关论文
共 35 条
  • [1] The chemistry of tea flavonoids
    Balentine, DA
    Wiseman, SA
    Bouwens, LCM
    [J]. CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, 1997, 37 (08) : 693 - 704
  • [2] Blot WJ, 1996, EUR J CANCER PREV, V5, P425
  • [3] Chen LS, 1997, DRUG METAB DISPOS, V25, P1045
  • [4] Chow HHS, 2001, CANCER EPIDEM BIOMAR, V10, P53
  • [5] Davis AL, 1996, MAGN RESON CHEM, V34, P887, DOI 10.1002/(SICI)1097-458X(199611)34:11<887::AID-OMR995>3.0.CO
  • [6] 2-U
  • [7] Analysis of (+)-catechin, (-)-epicatechin and their 3′- and 4′-O-methylated analogs -: A comparison of sensitive methods
    Donovan, JL
    Luthria, DL
    Stremple, P
    Waterhouse, AL
    [J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 1999, 726 (1-2): : 277 - 283
  • [8] Catechin is metabolized by both the small intestine and liver of rats
    Donovan, JL
    Crespy, V
    Manach, C
    Morand, C
    Besson, C
    Scalbert, A
    Rémésy, C
    [J]. JOURNAL OF NUTRITION, 2001, 131 (06) : 1753 - 1757
  • [9] Identification of the major antioxidative metabolites in biological fluids of the rat with ingested (+)-catechin and (-)-epicatechin
    Harada, M
    Kan, Y
    Naoki, H
    Fukui, Y
    Kageyama, N
    Nakai, M
    Miki, W
    Kiso, Y
    [J]. BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 1999, 63 (06) : 973 - 977
  • [10] Antioxidative activity of (-)-epigallocatechin-3-(3"-O-methyl)gallate isolated from fresh tea leaf and preliminary results on its biological activity
    Kawase, M
    Wang, R
    Shiomi, T
    Saijo, R
    Yagi, K
    [J]. BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2000, 64 (10) : 2218 - 2220