Cheng Zhongzhe, Zhou Xing, Du Zhifeng, Li Wenyi, Hu Bingying, Tian Jingkui, Zhang Lin, Huang Jiangeng, Jiang Hongliang
School of Pharmacy, Weifang Medical University, 7166 Baotong West Street, Weifang 261053, Shandong, China.
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, China.
Pharmaceutics. 2018 Oct 8;10(4):178. doi: 10.3390/pharmaceutics10040178.
Capilliposide B (LC-B) and Capilliposide C (LC-C), two new triterpenoid saponins extracted from 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.
从旋花科植物中提取的两种新的三萜皂苷——细梗丝石竹皂苷B（LC - B）和细梗丝石竹皂苷C（LC - C），在体外和体内均表现出潜在的抗癌活性。然而，它们的代谢过程仍不清楚。在本研究中，分别在人、大鼠和小鼠肝微粒体中研究了LC - B、LC - C和细梗丝石竹皂苷A（LC - A，LC - B和LC - C的生物活性代谢产物）的代谢稳定性。此后，在小鼠口服给药后对其代谢产物进行了鉴定和表征。结果发现，LC - B和LC - C的代谢稳定性存在种属差异。这三种目标化合物在人及大鼠肝微粒体中均稳定，但LC - B和LC - C在小鼠肝微粒体中显著降解。LC - B和LC - C的代谢不稳定性主要由酯解引起。此外，在小鼠生物基质中鉴定并表征了19种代谢产物。LC - B和LC - C主要发生去糖基化和酯解反应，同时伴有脱水、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。我们的研究结果更新了LC - B和LC - C的临床前代谢及处置过程，为更好地理解其疗效和安全性提供了更多信息。
