Metabolic profiling of tenacigenin B, tenacissoside H and tenacissoside I using UHPLC-ESI-Orbitrap MS/MS.
Metabolic profiling of tenacigenin B, tenacissoside H and tenacissoside I using UHPLC-ESI-Orbitrap MS/MS.
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DOI：
10.1002/bmc.3750
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发表时间：
2016-11
期刊：
影响因子：
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通讯作者：
Can Zhao;Ling Han;Wei-guang Ren;Haiyu Zhao;Shu-yan Han;Wen-xian Zheng;Lina Pang;Xiaohong Li;Ping-ping Li
中科院分区：
文献类型：
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作者：
Can Zhao;Ling Han;Wei-guang Ren;Haiyu Zhao;Shu-yan Han;Wen-xian Zheng;Lina Pang;Xiaohong Li;Ping-ping Li
马尾草是一种被广泛应用的抗癌中药，已被证明具有抗癌活性。然而，对其代谢谱的研究很少。Tenacigenin B是M. tenacissima C-21类固醇的主要类固醇骨架。tenacisso苷H和tenacisso苷I在tenacissima中检测到相对较高的水平。因此，我们采用超高效液相色谱-高分辨率质谱联用技术研究了它们在人肝微粒体中的代谢特性。通过精确的质量测量和MS/MS破碎行为初步鉴定了14种代谢物。结果表明，天那健苷H和天那健苷I在人肝微粒体中的代谢途径主要为羟基化反应，而天那健苷B的代谢途径主要为脱氢反应。这是首次在人肝微粒体中探索M. tenacissima中C-21类固醇的代谢谱，对后续的药代动力学和相互作用研究具有重要意义。体内或体外的生物转化可能影响化合物的结构并改变其活性。它们的断裂行为和代谢产物的鉴定为进一步了解田芽草的抗肿瘤活性提供了有价值的新信息。版权所有©2016 John Wiley & Sons， Ltd。
Marsdenia tenacissima, which is widely used as an anticancer herb in traditional Chinese medicine, has been shown to possess anticancer activity. However, its metabolic profile is poorly investigated. Tenacigenin B is the major steroidal skeleton of C-21 steroids in M. tenacissima. Tenacissoside H and Tenacissoside I are detected at relatively high levels in M. tenacissima. Therefore, we studied their metabolic characteristics in human liver microsomes by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. Fourteen metabolites were tentatively identified by accurate mass measurement and MS/MS fragmentation behavior. It was found that hydroxylation reactions were the major metabolic pathway of Tenacissoside H and Tenacissoside I in human liver microsomes, whereas the metabolic pathway of Tenacigenin B involved dehydrogenation reactions. This is the first time that the metabolic profile of C-21 steroids from M. tenacissima has been explored in human liver microsomes, which is of great significance for subsequent pharmacokinetic and interaction research. Biotransformation in vivo or in vitro may influence the structure of a compound and change its activity. Identification of their fragmentation behaviors and metabolites provides valuable and new information for further understanding the anti-tumor activity of M. tenacissima. Copyright © 2016 John Wiley & Sons, Ltd.