朝鲜淫羊藿潜在肝毒性成分在不同种属肝微粒体中体外代谢稳定性研究  

Study on metabolic stability in vitro of potential hepatotoxicity components of Epimedium koreanum Nakai in liver microsomes among different species

作　　者：张林 康倩君 涂灿 郭兆娟 王停 ZHANG Lin;KANG Qianjun;TU Can;GUO Zhaojuan;WANG Ting(Beijing Institute of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学北京中医药研究院,北京102488

出　　处：《中华中医药杂志》2023年第11期5469-5473,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.82004053);北京市自然科学基金面上项目(No.7222277)。

摘　　要：目的:应用不同种属肝微粒体,研究朝鲜淫羊藿中潜在肝毒性成分箭藿苷A、淫羊藿次苷Ⅰ、宝藿苷Ⅰ体外代谢稳定性,探讨肝脏代谢对毒性成分的影响及体外代谢种属差异。方法:将朝鲜淫羊藿提取物分别与小鼠、SD大鼠、人、恒河猴、Beagle犬肝微粒体进行孵育,采用底物消除法考察箭藿苷A、淫羊藿次苷Ⅰ、宝藿苷Ⅰ剩余底物浓度随时间的变化,计算各成分体外消除半衰期(t_(1/2)),分析各成分代谢稳定性特征。结果:箭藿苷A以Ⅰ相代谢为主,人肝微粒体中最终剩余底物浓度占比为32.33%,t_(1/2)为37.26 min,淫羊藿次苷Ⅰ以Ⅰ相代谢为主,人肝微粒体中最终代谢完全,t_(1/2)为4.47 min,宝藿苷Ⅰ以Ⅱ相代谢为主,人肝微粒体中最终剩余底物浓度占比为10.39%,t_(1/2)为19.47 min;各成分在Beagle犬肝微粒体中的代谢特征与在人肝微粒体中的较为相近。结论:箭藿苷A受代谢消除影响较小,可发挥固有毒性,而淫羊藿次苷Ⅰ和宝藿苷Ⅰ的固有毒性因代谢消除而减弱,证实了肝脏代谢对朝鲜淫羊藿潜在肝毒性成分毒性的影响,并为体内代谢研究及动物模型选择提供参考。Objective:To probe the effect of metabolism on potential hepatotoxic components of Epimedium koreanum Nakai and species difference,the metabolic stability of sagitatoside A,icarisid I and baohuoside I in vitro was studied by employing incubated different species of liver microsomes.Methods:Sagittatoside A,icarisid I and baohuoside I were separately incubated with mouse,SD rat,human,rhesus monkey or Beagle dog liver microsomes,and then the remaining percentage changes over time were evaluated using a substrate depletion approach and the in vitro half-life(t_(1/2))were calculated to analysis the metabolism characteristics.Results:The results showed that,the major metabolic types of sagittatoside A was phase I,of which the percent of remaining was 32.33%and t_(1/2) was 37.26 min in human liver microsomes.Icarisid I was phase I,which was depleted among the range of incubating time,and t_(1/2) was 4.47 min in human liver microsomes.Baohuoside I was phase I,of which the percent of remaining in human liver microsomes was 10.39%and t_(1/2) was 19.47 min.The metabolic characteristics of these components in Beagle dog were similar to those in human.Conclusion:The effect of metabolism on sagittatoside A was less,so it could play the hepatotoxicity as the original form in vivo.While the toxicity of icarisid I and baohuoside I would be weakened due to stronger metabolic elimination.It followed that the hepatotoxicity of the studied components of Epimedium koreanum Nakai could be influenced by the liver metabolism and the results provided the reference for the research in vivo and the choice of model animal.

关 键 词：朝鲜淫羊藿 肝毒性 肝微粒体 代谢稳定性 种属差异 

分 类 号：R285.5[医药卫生—中药学]