Drug-Drug Interactions Potential of Icariin and Its Intestinal Metabolites via Inhibition of Intestinal UDP-Glucuronosyltransferases.
Drug-Drug Interactions Potential of Icariin and Its Intestinal Metabolites via Inhibition of Intestinal UDP-Glucuronosyltransferases.
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淫羊藿苷及其肠道代谢物通过抑制肠道 UDP-葡萄糖醛酸基转移酶的药物相互作用潜力
DOI：
10.1155/2012/395912
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Cao YF;He RR;Cao J;Chen JX;Huang T;Liu Y
淫羊藿苷是已知的淫羊藿属的指示性成分，其已被常用在中草药中以增强治疗阳痿和改善性功能，以及用于超过2000年的其他几种适应症。本研究旨在探讨淫羊藿苷及其肠道代谢产物对人尿苷二磷酸葡萄糖醛酸转移酶（UGT）活性的影响。使用一组重组人UGT亚型，我们发现淫羊藿苷对UGT1A3表现出强效抑制作用。有趣的是，淫羊藿苷的肠代谢产物与淫羊藿苷相比表现出不同的抑制曲线。与淫羊藿苷不同，淫羊藿苷II是UGT 1A4、UGT 1A7、UGT 1A9和UGT 2B7的有效抑制剂，淫羊藿苷是UGT 1A7和UGT 1A9的有效抑制剂。还定量预测和比较了体内药物相互作用的可能性。风险的定量预测表明，口服淫羊藿苷产品后可能会发生对肠道UGT 1A3、UGT 1A4和UGT 1A7的体内抑制。
Icariin is known as an indicative constituent of the Epimedium genus, which has been commonly used in Chinese herbal medicine to enhance treat impotence and improve sexual function, as well as for several other indications for over 2000 years. In this study, we aimed to investigate the effects of icariin and its intestinal metabolites on the activities of human UDP-glucuronosyltransferase (UGT) activities. Using a panel of recombinant human UGT isoforms, we found that icariin exhibited potent inhibition against UGT1A3. It is interesting that the intestinal metabolites of icariin exhibited a different inhibition profile compared with icariin. Different from icariin, icariside II was a potent inhibitor of UGT1A4, UGT1A7, UGT1A9, and UGT2B7, and icaritin was a potent inhibitor of UGT1A7 and UGT1A9. The potential for drug interactions in vivo was also quantitatively predicted and compared. The quantitative prediction of risks indicated that in vivo inhibition against intestinal UGT1A3, UGT1A4, and UGT1A7 would likely occur after oral administration of icariin products.