Sakaki Toshiyuki, Yasuda Kaori, Nishikawa Miyu, Ikushiro Shinichi
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University.
Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University.
Yakugaku Zasshi. 2018;138(3):357-363. doi: 10.1248/yakushi.17-00191-4.
Sesamin, derived from sesame seeds, is known to have various biological effects. Since some of these effects appear to be derived from its metabolites, the elucidation of sesamin metabolism is essential to understanding the molecular mechanism of its effects. In addition, it is important to clarify drug-sesamin interactions in order to address safety concerns, as some food factors are known to affect drug metabolism. Our previous studies revealed that sesamin was sequentially metabolized by cytochrome P450 (CYP) and UDP-glucuronosyltransferase or sulfotransferase. Whereas sesamin metabolism is mainly mediated by CYP2C9 in human liver, sesamin causes a mechanism-based inhibition (MBI) of CYP2C9. However, we found that the metabolite-intermediate complex between CYP2C9 and sesamin was unstable, and the effects of sesamin appeared to be minimal. To confirm this assumption, in vivo studies using rats were conducted. After the administration of sesamin to rats for 3 d, diclofenac (an NSAID) was administered to measure the time course of plasma concentration of diclofenac. No significant differences were observed in the diclofenac C, T, and AUC between the group that was administered sesamin and the group that was not. Based on these results, it could be concluded that no significant interaction occurs in people who take sesamin supplements at a standard dose.
芝麻素源自芝麻籽，已知具有多种生物学效应。由于其中一些效应似乎源自其代谢产物，因此阐明芝麻素的代谢对于理解其效应的分子机制至关重要。此外，由于已知某些食物成分会影响药物代谢，为解决安全性问题，阐明药物与芝麻素之间的相互作用也很重要。我们之前的研究表明，芝麻素会依次被细胞色素P450（CYP）和尿苷二磷酸葡萄糖醛酸基转移酶或磺基转移酶代谢。虽然在人肝脏中芝麻素代谢主要由CYP2C9介导，但芝麻素会对CYP2C9产生基于机制的抑制（MBI）。然而，我们发现CYP2C9与芝麻素之间的代谢物-中间体复合物不稳定，芝麻素的影响似乎很小。为了证实这一假设，我们使用大鼠进行了体内研究。给大鼠连续3天服用芝麻素后，再给予双氯芬酸（一种非甾体抗炎药）以测量双氯芬酸血浆浓度的时间进程。服用芝麻素的组与未服用芝麻素的组之间，双氯芬酸的C、T和AUC均未观察到显著差异。基于这些结果，可以得出结论，以标准剂量服用芝麻素补充剂的人不会发生显著的相互作用。
