Zhang Zhaowei, Fang Tianzi, Zhou Hongyun, Yuan Jie, Liu Qingwang
Department of Pharmacy, Jinhua Municipal Central Hospital, Jinhua, China.
Anhui Provincial Institute for Food and Drug Control, Hefei, China.
Front Pharmacol. 2018 Feb 22;9:130. doi: 10.3389/fphar.2018.00130. eCollection 2018.
Evodiamine is an indoloquinazoline alkaloid isolated from the fruit of , which has a wide range of pharmacological effects like anti-tumor and anti-inflammatory effects. This study was intended to investigate the metabolic characteristics of evodiamine in human liver microsomes and hepatocytes by ultra-high performance liquid chromatography coupled with a Q Exactive mass spectrometer. A total of 12 phase I metabolites were detected in human liver microsomes; whereas in human hepatocytes 19 metabolites, including seven phase II metabolites were detected. The structures of the metabolites were characterized based on their accurate masses, fragment ions, and chromatographic retention times. Four metabolites (M1, M2, M5, and M7) were further unambiguously confirmed by matching their retention times, accurate masses, and fragment ions with those of their reference standards. Among these metabolites, 12 metabolites are first identified (M2, M5-M8, M10-M13, and M17-M19). The current study revealed that oxygenation, -demethylation, dehydrogenation, glucuronidation, and GSH conjugation were the major metabolic pathways for evodiamine. This study elucidated the detailed metabolite profiles of evodiamine, which is helpful in predicting metabolism of evodiamine in human and in understanding the elimination mechanism of evodiamine and in turn, the effectiveness and toxicity.
吴茱萸碱是一种从吴茱萸果实中分离得到的吲哚喹唑啉生物碱，具有广泛的药理作用，如抗肿瘤和抗炎作用。本研究旨在通过超高效液相色谱联用Q Exactive质谱仪研究吴茱萸碱在人肝微粒体和肝细胞中的代谢特征。在人肝微粒体中总共检测到12种I相代谢产物；而在人肝细胞中检测到19种代谢产物，包括7种II相代谢产物。根据代谢产物的精确质量、碎片离子和色谱保留时间对其结构进行了表征。通过将4种代谢产物（M1、M2、M5和M7）的保留时间、精确质量和碎片离子与其参考标准品进行匹配，进一步明确确认了它们的结构。在这些代谢产物中，有12种代谢产物是首次鉴定（M2、M5-M8、M10-M13和M17-M19）。目前的研究表明，氧化、去甲基化、脱氢、葡萄糖醛酸化和谷胱甘肽结合是吴茱萸碱的主要代谢途径。本研究阐明了吴茱萸碱详细的代谢产物谱，这有助于预测吴茱萸碱在人体内的代谢，理解吴茱萸碱的消除机制，进而了解其有效性和毒性。
