Suberosin is a natural prenylated coumarin derivative isolated from Citropsis articulata. It has various pharmacological properties, especially as an anticoagulant, for which it has been used since antiquity. However, its metabolic pathway and metabolites have not yet been studied. Therefore, this study characterizes its metabolic pathway and metabolites in human liver microsomes (HLMs) using high‐resolution quadrupole–orbitrap mass spectrometry (HRMS/MS). Eight metabolites (M1–M8) were found, including three monohydroxylated (M1–M3), one hydrated (M4), three dihydroxylated (M5–M7), and one glucuronide conjugate (M8). Furthermore, forms of cytochrome P450 (CYPs) responsible for suberosin metabolism in HLMs were characterized. CYP1A2 was identified as a major enzyme for the production of M1 and M5 metabolites. The M2, M3, and M7 metabolites were predominantly generated by CYP2B6. M8 was the only phase II metabolite, identified as a glucuronide conjugate from either M1 or M2. This glucuronide conjugate may be the only promising metabolite from phase II metabolism. Phase I metabolism, especially hydroxylation, was found to provide a predominant metabolic pathway of suberosin in HLMs. Further studies should be conducted to explore the metabolites, examining their efficacy and their toxicity in an in vivo system.

中文翻译：

---

高效液相色谱结合高分辨率四极杆-轨道阱质谱仪鉴定人肝微粒体中木栓素代谢物

Suberosin 是一种从Citropsis articulata 中分离出来的天然异戊二烯化香豆素衍生物。它具有多种药理特性，特别是作为抗凝剂，自古以来就被用于抗凝剂。然而，尚未对其代谢途径和代谢产物进行研究。因此，本研究使用高分辨率四极杆轨道阱质谱 (HRMS/MS) 表征其在人肝微粒体 (HLM) 中的代谢途径和代谢物。发现了八种代谢物 (M1–M8)，包括三种单羟基化 (M1–M3)、一种水合 (M4)、三种二羟基化 (M5–M7) 和一种葡萄糖醛酸结合物 (M8)。此外，表征了 HLM 中负责木栓素代谢的细胞色素 P450 (CYPs) 的形式。CYP1A2 被鉴定为产生 M1 和 M5 代谢物的主要酶。M2、M3 和 M7 代谢物主要由 CYP2B6 产生。M8 是唯一的 II 期代谢物，鉴定为来自 M1 或 M2 的葡萄糖醛酸结合物。这种葡萄糖醛酸结合物可能是来自 II 期代谢的唯一有希望的代谢物。发现 I 期代谢，尤其是羟基化，提供了 HLM 中木栓质的主要代谢途径。应进行进一步研究以探索代谢物，检查其在体内系统中的功效和毒性。