Chen Bo, Guo Jingjing, Wang Shibo, Kang Liting, Deng Yulin, Li Yujuan
School of Life Science, Beijing Institute of Technology, Beijing, China.
Front Pharmacol. 2018 Oct 12;9:1130. doi: 10.3389/fphar.2018.01130. eCollection 2018.
Loureirin B (LB) is the marker compound of dragon blood (DB), which exhibits great potentials in protecting astronauts' health against radiation and simulated microgravity (SM). Pharmacokinetics of LB is reported to be significantly altered by SM. Here, we investigated key metabolic features of LB in rat liver microsome (RLM) and the effects of SM on LB metabolism as well as on expression of major hepatic cytochrome P450 (CYP450) isoforms. Ten metabolites were tentatively identified based on fragmentation pathways using LC-MS/MS method and elimination kinetics of LB followed a typical Michaelis-Menten equation ( was 1.32 μg/min/mg and was 13.33 μg/mL). CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were involved in the metabolism of LB and the relative strength was: CYP3A2 > CYP2C11 > CYP2D1 > CYP1A2. Comparative studies suggested that elimination of LB in RLM was remarkably increased by 3-day and 14-day SM, and the generation of identified metabolites was affected as well. Additionally, 3-day and 14-day SM showed obvious regulatory effects on the expression of major CYP450 isoforms, which might contribute to the increased elimination of LB. The data provided supports for the application of DB as a protective agent and the reasonable use of current medications metabolized by hepatic CYP450 in space missions.
龙血素B（LB）是血竭（DB）的标志性化合物，在保护宇航员健康免受辐射和模拟微重力（SM）影响方面具有巨大潜力。据报道，SM会显著改变LB的药代动力学。在此，我们研究了LB在大鼠肝微粒体（RLM）中的关键代谢特征，以及SM对LB代谢和主要肝细胞色素P450（CYP450）同工酶表达的影响。使用LC-MS/MS方法根据裂解途径初步鉴定出10种代谢物，LB的消除动力学遵循典型的米氏方程（Vmax为1.32μg/分钟/毫克，Km为13.33μg/mL）。CYP1A2、CYP2C11、CYP2D1和CYP3A2参与了LB的代谢，相对强度为：CYP3A2>CYP2C11>CYP2D1>CYP1A2。比较研究表明，3天和14天的SM显著增加了RLM中LB的消除，且已鉴定代谢物的生成也受到影响。此外，3天和14天的SM对主要CYP450同工酶的表达显示出明显的调节作用，这可能有助于增加LB的消除。所提供的数据为DB作为一种保护剂的应用以及在太空任务中合理使用由肝脏CYP450代谢的现有药物提供了支持。
