State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Molecules. 2020 Jan 30;25(3):606. doi: 10.3390/molecules25030606.
The importance of the gut microbiota in drug metabolism, especially in that of nonabsorbable drugs, has become known. The aim of this study was to explore the metabolites of triptolide by the gut microbiota. With high-performance liquid chromatography coupled with tandem mass spectrometry and ion trap time-of-flight multistage mass spectrometry (LC-MS/MS and LC/MS-IT-TOF), four metabolites of triptolide (M1, M2, M3, and M4) were found in the intestinal contents of rats. M1 and M2, were isomeric monocarbonyl-hydroxyl-substituted metabolites with molecular weights of 390. M3 and M4 were isomeric dehydrogenated metabolites with molecular weights of 356. Among the four metabolites, the dehydrogenated metabolites (M3 and M4) were reported in the gut microbiota for the first time. The metabolic behaviors of triptolide in the gut microbiota and liver microsomes of rats were further compared. The monocarbonyl-hydroxyl-substituted metabolites (M1 and M2) were generated in both systems, and another monohydroxylated metabolite (M5) was found only in the liver microsomes. The combined results suggested that the metabolism of triptolide in the gut microbiota was specific, with two characteristic, dehydrogenated metabolites. This investigation might provide a theoretical basis for the elucidation of the metabolism mechanism of triptolide and guide its proper application in clinical administration.
肠道微生物群在药物代谢中的重要性，尤其是在不吸收药物的代谢中，已广为人知。本研究旨在探索肠道微生物群对雷公藤红素的代谢产物。采用高效液相色谱-串联质谱和离子阱飞行时间多级质谱（LC-MS/MS 和 LC/MS-IT-TOF），在大鼠肠内容物中发现了雷公藤红素的 4 种代谢产物（M1、M2、M3 和 M4）。M1 和 M2 为异构单羰基-羟基取代代谢物，分子量为 390。M3 和 M4 为异构脱氢代谢物，分子量为 356。在这 4 种代谢产物中，脱氢代谢物（M3 和 M4）是首次在肠道微生物群中报道的。进一步比较了雷公藤红素在大鼠肠道微生物群和肝微粒体中的代谢行为。在这两个系统中都生成了单羰基-羟基取代代谢物（M1 和 M2），而另一种单羟基化代谢物（M5）仅在肝微粒体中发现。综合结果表明，雷公藤红素在肠道微生物群中的代谢具有特异性，产生了两种特征性的脱氢代谢物。这项研究可能为雷公藤红素代谢机制的阐明提供理论依据，并指导其在临床给药中的合理应用。
