Zhu B T, Taneja N, Loder D P, Balentine D A, Conney A H
Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway 08855, USA.
J Steroid Biochem Mol Biol. 1998 Feb;64(3-4):207-15. doi: 10.1016/s0960-0760(97)00163-5.
Administration of 0.5 or 1% lyophilized green tea (5 or 10 mg tea solids per ml, respectively) as the sole source of drinking fluid to female Long-Evans rats for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 30-37%, 15-27% and 26-60%, respectively. Oral administration of 0.5% lyophilized green tea to female CD-1 mice for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 33-37%, 12-22% and 172-191%, respectively. The in vitro addition of a green tea polyphenol mixture, a black tea polyphenol mixture or (-)-epigallocatechin gallate inhibited rat liver microsomal glucuronidation of estrone and estradiol in a concentration-dependent manner and their IC50 values for inhibition of estrogen metabolism were approximately 12.5, 50 and 10 microg/ml, respectively. Enzyme kinetic analysis indicates that the inhibition of estrone glucuronidation by 10 microM (-)-epigallocatechin gallate was competitive while inhibition by 50 microM (-)-epigallocatechin gallate was noncompetitive. Similarly, several flavonoids (naringenin, hesperetin, kaempferol, quercetin, rutin, flavone, alpha-naphthoflavone and beta-naphthoflavone) also inhibited rat liver microsomal glucuronidation of estrone and estradiol to varying degrees. Naringenin and hesperetin displayed the strongest inhibitory effects (IC50 value of approximately 25 microM). These two hydroxylated flavonoids had a competitive mechanism of enzyme inhibition for estrone glucuronidation at a 10 microM inhibitor concentration and a predominantly noncompetitive mechanism of inhibition at a 50 microM inhibitor concentration.
以0.5%或1%的冻干绿茶（分别为每毫升5或10毫克茶固体）作为唯一饮用水源，给雌性Long-Evans大鼠饮用18天，可分别使雌酮、雌二醇和4-硝基苯酚的肝脏微粒体葡萄糖醛酸化作用增强30 - 37%、15 - 27%和26 - 60%。给雌性CD-1小鼠口服0.5%的冻干绿茶18天，可分别使雌酮、雌二醇和4-硝基苯酚的肝脏微粒体葡萄糖醛酸化作用增强33 - 37%、12 - 22%和172 - 191%。体外添加绿茶多酚混合物、红茶多酚混合物或（-）-表没食子儿茶素没食子酸酯，可浓度依赖性地抑制大鼠肝脏微粒体对雌酮和雌二醇的葡萄糖醛酸化作用，它们抑制雌激素代谢的IC50值分别约为12.5、50和10微克/毫升。酶动力学分析表明，10微摩尔（-）-表没食子儿茶素没食子酸酯对雌酮葡萄糖醛酸化作用的抑制为竞争性抑制，而50微摩尔（-）-表没食子儿茶素没食子酸酯的抑制为非竞争性抑制。同样，几种黄酮类化合物（柚皮素、橙皮素、山奈酚、槲皮素、芦丁、黄酮、α-萘黄酮和β-萘黄酮）也不同程度地抑制大鼠肝脏微粒体对雌酮和雌二醇的葡萄糖醛酸化作用。柚皮素和橙皮素表现出最强的抑制作用（IC50值约为25微摩尔）。这两种羟基化黄酮类化合物在10微摩尔抑制剂浓度下对雌酮葡萄糖醛酸化作用的酶抑制机制为竞争性，在50微摩尔抑制剂浓度下主要为非竞争性抑制机制。
