Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC⁻QTRAP⁻MS/MS.
Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC⁻QTRAP⁻MS/MS.
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通过 LC→QTRAP→MS/MS 测定 Capilliposide B 和 Capilliposide C 的代谢稳定性和代谢物表征
DOI：
10.3390/pharmaceutics10040178
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发表时间：
2018-10-08
期刊：
影响因子：
5.4
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Cheng Z;Zhou X;Du Z;Li W;Hu B;Tian J;Zhang L;Huang J;Jiang H
毛细管藻三萜皂苷B(LC-B)和毛细管菌素C(LC-C)是从金钱草中分离得到的两种新的三萜皂苷，具有潜在的体内外抗癌活性。然而，它们的代谢过程仍不清楚。在本研究中，分别考察了LC-B、LC-C和毛细菌素A(LC-A，LC-B和LC-C的活性代谢物)在人、大鼠和小鼠肝微粒体中的代谢稳定性。然后，在小鼠口服给药后，对其代谢物进行鉴定和表征。结果表明，LC-B和LC-C的代谢稳定性存在物种差异。这三种化合物在人和大鼠肝微体中都是稳定的，但LC-B和LC-C在小鼠肝微体中显著降解。LC-B和LC-C的代谢不稳定主要是由酯解作用引起的。此外，在小鼠生物基质中还鉴定了19种代谢物。LC-B和LC-C主要发生脱糖和酯解反应，并伴有脱水、脱氢和羟基化等次要代谢反应。最后，提出了LC-B和LC-C在小鼠体内的代谢途径。我们的结果更新了LC-B和LC-C的临床前代谢和处置过程，为更好地了解疗效和安全性提供了额外的信息。
Capilliposide B (LC-B) and Capilliposide C (LC-C), two new triterpenoid saponins extracted from Lysimachia capillipes Hemsl, exhibit potential anticancer activity both in vitro and in vivo. However, their metabolic process remains unclear. In this study, the metabolic stability of LC-B, LC-C, and Capilliposide A (LC-A, a bioactive metabolite of LC-B and LC-C) was investigated in human, rat, and mouse liver microsomes, respectively. Thereafter, their metabolites were identified and characterized after oral administration in mice. As a result, species difference was found in the metabolic stability of LC-B and LC-C. All three compounds of interest were stable in human and rat liver microsomes, but LC-B and LC-C significantly degraded in mouse liver microsomes. The metabolic instability of LC-B and LC-C was mainly caused by esterolysis. Moreover, 19 metabolites were identified and characterized in mouse biological matrices. LC-B and LC-C mainly underwent deglycosylation and esterolysis, accompanied by dehydration, dehydrogenation, and hydroxylation as minor metabolic reactions. Finally, the metabolic pathway of LC-B and LC-C in mice was proposed. Our results updated the preclinical metabolism and disposition process of LC-B and LC-C, which provided additional information for better understanding efficacy and safety.
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影响因子：
3.1
作者：
Liang, Bo;Zhang, Lin;Yang, Shilin
通讯作者：
Yang, Shilin
DOI：
10.12659/msm.901183
发表时间：
2017-05-02
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Shen Z;Xu L;Li J;Zhang N
通讯作者：
Zhang N
影响因子：
1.8
作者：
Cheng, Zhongzhe;Zhou, Xing;Jiang, Hongliang
通讯作者：
Jiang, Hongliang
DOI：
10.1016/j.jpba.2016.07.048
发表时间：
2016-09-10
影响因子：
3.4
作者：
Chen, Guiying;Cheng, Zhongzhe;Zhu, Mingshe
通讯作者：
Zhu, Mingshe
DOI：
10.3969/j.issn.1001-1978.2012.04.024
发表时间：
2012-04-01
期刊：
Zhongguo Yaolixue Tongbao
影响因子：
--
作者：
Xu Yan;Rong Yu-mei;Tian Jing-kui
通讯作者：
Tian Jing-kui