Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of estradiol and estrone.
Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of estradiol and estrone.
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茶多酚和黄酮类化合物对雌二醇和雌酮肝微粒体葡萄糖醛酸化的影响。
DOI：
10.1016/s0960-0760(97)00163-5
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Conney,AH
中科院分区：
文献类型：
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作者：
Zhu,BT;Taneja,N;Loder,DP;Balentine,DA;Conney,AH
将 0.5 或 1% 冻干绿茶（每毫升分别含 5 或 10 毫克茶固体）作为雌性 Long-Evans 大鼠的唯一饮用液体来源 18 天，可刺激肝微粒体中雌酮、雌二醇和 4-硝基苯酚的葡萄糖醛酸化作用，分别提高 30-37%、15-27% 和 26-60%。雌性 CD-1 小鼠口服 0.5% 冻干绿茶 18 天，可刺激肝脏微粒体中雌酮、雌二醇和 4-硝基苯酚的葡萄糖醛酸化作用分别提高 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，以浓度依赖性方式抑制大鼠肝微粒体雌酮和雌二醇的葡萄糖醛酸化，抑制雌激素代谢的IC50值分别约为12.5、50和10μg/ml。酶动力学分析表明，10 μM (−)-表没食子儿茶素没食子酸酯对雌酮葡萄糖醛酸化的抑制是竞争性的，而50 μM (−)-表没食子儿茶素没食子酸酯的抑制是非竞争性的。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微粒体中雌酮和雌二醇的葡萄糖醛酸化。柚皮素和橙皮素表现出最强的抑制作用（ic50值约为25μM）。这两种羟基化黄酮类化合物在 10μM 抑制剂浓度下对雌酮葡萄糖醛酸化具有竞争性酶抑制机制，在 50μM 抑制剂浓度下具有显着的非竞争性抑制机制。
Administration of 0.5 or 1% lyophilized green tea (5 or 10mg tea solids per ml, respectively) as the sole source of drinking fluid to female Long–Evans rats for 18days 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 18days 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 ic50values for inhibition of estrogen metabolism were approximately 12.5, 50 and 10μg/ml, respectively. Enzyme kinetic analysis indicates that the inhibition of estrone glucuronidation by 10 μM (−)-epigallocatechin gallate was competitive while inhibition by 50μM (−)-epigallocatechin gallate was noncompetitive. Similarly, several flavonoids (naringenin, hesperetin, kaempferol, quercetin, rutin, flavone, α-naphthoflavone and β-naphthoflavone) also inhibited rat liver microsomal glucuronidation of estrone and estradiol to varying degrees. Naringenin and hesperetin displayed the strongest inhibitory effects (ic50value of approximately 25μM). These two hydroxylated flavonoids had a competitive mechanism of enzyme inhibition for estrone glucuronidation at a 10μM inhibitor concentration and a predominantly noncompetitive mechanism of inhibition at a 50μM inhibitor concentration.