Yasuda Kaori, Okamoto Kairi, Ueno Sera, Itoh Kasumi, Nishikawa Miyu, Ikushiro Shinichi, Sakaki Toshiyuki
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Drug Metab Pharmacokinet. 2019 Apr;34(2):134-140. doi: 10.1016/j.dmpk.2018.12.004. Epub 2018 Dec 31.
Sesamin is known to have various biological effects. Although several metabolites of sesamin have been identified, its metabolism by phase II enzymes remains unclear, because usually its sulfo- and glucurono-conjugates in plasma and urine are analyzed after sulfatase/β-glucuronidase treatment. In this study, the metabolites of sesamin in rats administrated with sesamin (100 mg/kg b.w.) were analyzed without sulfatase/β-glucuronidase treatment. Two sulfate conjugates of sesamin monocatechol (SC-1) were detected in the liver and plasma. Their C values were 5- and 10-times higher than that of sesamin itself. The V/K values for sulfate conjugation in the cytosol fraction of human liver were 1.7-times larger than that in the cytosol fraction of rat liver, suggesting that sulfate conjugation also occurs in human liver. The recombinant human proteins SULT1A1, 1A3, 1B1, and 1E1 expressed in Saccharomyces cerevisiae cells produced sulfate conjugates effectively. Our results could help revealing the mechanism of physiological effects of sesamin.
芝麻素具有多种生物学效应。尽管已鉴定出芝麻素的几种代谢产物，但其经Ⅱ相酶的代谢仍不清楚，因为通常在硫酸酯酶/β-葡萄糖醛酸酶处理后分析血浆和尿液中的硫酸酯和葡萄糖醛酸结合物。在本研究中，对给予芝麻素（100mg/kg体重）的大鼠体内芝麻素的代谢产物进行了分析，未进行硫酸酯酶/β-葡萄糖醛酸酶处理。在肝脏和血浆中检测到了芝麻素单儿茶酚的两种硫酸酯结合物（SC-1）。它们的C值比芝麻素本身高5倍和10倍。人肝细胞溶质部分硫酸酯化的V/K值比大鼠肝细胞溶质部分大1.7倍，表明人肝脏中也发生硫酸酯化。在酿酒酵母细胞中表达的重组人蛋白SULT1A1、1A3、1B1和1E1能有效产生硫酸酯结合物。我们的结果有助于揭示芝麻素生理效应的机制。
