Shi Wei, Ling Jie, Jiang Li-Long, Zhao Dong-Sheng, Wang Ling-Li, Wu Zi-Tian, Li Ping, Wei Ying-Jie, Li Hui-Jun
State Key Laboratory of Natural Medicines, China Pharmaceutical University No. 24 Tongjia Lane Nanjing 210009 China
The Third Clinical School of Medicine, Nanjing University of Chinese Medicine 100 Shizi Street Nanjing 210028 China
RSC Adv. 2018 Feb 19;8(14):7765-7773. doi: 10.1039/c7ra12910f. eCollection 2018 Feb 14.
Diterpenoid lactones (DLs) have been reported to be the main hepatotoxic constituents in tubers (DBT), a traditional Chinese medicinal herb. The acquisition of early information regarding its metabolism is critical for evaluating the potential hepatotoxicity of DLs. We investigated, for the first time, the main metabolites of diosbulbin A (DIOA), diosbulbin C (DIOC), diosbulbin (DIOG), diosbulbin (DIOM) and diosbulbin (DIOF) in adult zebrafish. By using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS), 6, 2, 7, 5 and 4 metabolites of DIOA, DIOC, DIOF, DIOM and DIOG were identified in the zebrafish body and the aqueous solution, respectively. Both phase-I and phase-II metabolites were observed in the metabolic profiles and the metabolic pathways involved in hydroxyl reduction, glucuronidation, glutathione conjugation and sulfation. The above results indicated that hepatocytic metabolism might be the major route of clearance for DLs. This study provided important information for the understanding of the metabolism of DLs in DBT.
二萜类内酯（DLs）据报道是传统中草药黄独块茎（DBT）中的主要肝毒性成分。获取有关其代谢的早期信息对于评估DLs的潜在肝毒性至关重要。我们首次研究了成年斑马鱼中二氢黄独素A（DIOA）、二氢黄独素C（DIOC）、二氢黄独素G（DIOG）、二氢黄独素M（DIOM）和二氢黄独素F（DIOF）的主要代谢产物。通过使用超高效液相色谱-四极杆飞行时间质谱（UHPLC-QTOF MS），在斑马鱼体内和水溶液中分别鉴定出了DIOA、DIOC、DIOF、DIOM和DIOG的6种、2种、7种、5种和4种代谢产物。在代谢谱中观察到了I相和II相代谢产物，以及涉及羟基还原、葡萄糖醛酸化、谷胱甘肽结合和硫酸化的代谢途径。上述结果表明，肝细胞代谢可能是DLs清除的主要途径。本研究为理解DBT中DLs的代谢提供了重要信息。
