Vaidyanathan Jaya Bharathi, Walle Thomas
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA.
Drug Metab Dispos. 2002 Aug;30(8):897-903. doi: 10.1124/dmd.30.8.897.
(-)-Epicatechin (EC) is one of the flavonoids present in green tea, suggested to have chemopreventive properties in cancer. However, its bioavailability is not clearly understood. In the present study, we determined the metabolism of EC, focusing on its glucuronic acid and sulfate conjugation using human liver and intestinal microsomes and cytosol as well as recombinant UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) isoforms in comparison with that occurring in the rat. Surprisingly, EC was not glucuronidated by the human liver and small intestinal microsomes. There was also no evidence of glucuronidation by human colon microsomes or by recombinant UGT1A7, which is not present in the liver or intestine. Interestingly, in the rat liver microsomes EC was efficiently glucuronidated with the formation of two glucuronides. In contrast, the human liver cytosol efficiently sulfated EC mainly through the SULT1A1 isoform. For the intestine, both SULT1A1 and SULT1A3 contributed. Other SULT isoforms contributed little. High-performance liquid chromatography of the sulfate conjugates showed one major sulfatase-sensitive peak with all tissues. An additional minor sulfatase-resistant peak was formed by the liver and intestinal cytosol as well as with SULT1A1 but not by the Caco-2 cytosol and SULT1A3. In the rat, EC sulfation was considerably less efficient than in the human liver. These results indicate that sulfation is the major pathway in EC metabolism in the human liver and intestine with no glucuronidation occurring. There was also a large species difference both in glucuronidation and sulfation of EC between rats and humans.
（-）-表儿茶素（EC）是绿茶中含有的黄酮类化合物之一，被认为具有癌症化学预防特性。然而，其生物利用度尚不清楚。在本研究中，我们以人肝和肠微粒体及胞质溶胶以及重组尿苷二磷酸葡萄糖醛酸基转移酶（UGT）和磺基转移酶（SULT）同工型为研究对象，确定了EC的代谢情况，并与大鼠体内的代谢情况进行了比较，重点关注其葡萄糖醛酸和硫酸盐结合情况。令人惊讶的是，人肝和小肠微粒体未对EC进行葡萄糖醛酸化。也没有证据表明人结肠微粒体或重组UGT1A7（不存在于肝脏或肠道中）能对其进行葡萄糖醛酸化。有趣的是，在大鼠肝微粒体中，EC能高效地进行葡萄糖醛酸化，形成两种葡萄糖醛酸苷。相比之下，人肝细胞质主要通过SULT1A1同工型有效地将EC硫酸化。对于肠道，SULT1A1和SULT1A3都有作用。其他SULT同工型作用较小。硫酸盐结合物的高效液相色谱分析显示，所有组织都有一个主要的对硫酸酯酶敏感的峰。肝脏和肠道胞质溶胶以及SULT1A1还形成了一个额外的对硫酸酯酶有抗性的小峰，但Caco-2胞质溶胶和SULT1A3没有。在大鼠中，EC的硫酸化效率远低于人肝脏。这些结果表明，硫酸化是人肝脏和肠道中EC代谢的主要途径，不存在葡萄糖醛酸化。大鼠和人在EC的葡萄糖醛酸化和硫酸化方面也存在很大的种属差异。
