Gao Hua, Zhang Lei, Zhu An, Liu Xiaoyan, Wang Tianxia, Wan Meiqi, Yang Xiuwei, Zhang Yingtao, Zhang Youbo
State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China.
J Agric Food Chem. 2020 Nov 18. doi: 10.1021/acs.jafc.0c04468.
Nuciferine (NF) is one of the main constituents of Lotus () leaves which have been widely used in both food and drug formulations in China. Although possessing a broad spectrum of bioactivities, the metabolic characteristics of NF are inadequately unknown after oral gavage with this NF. The present study was performed to characterize its metabolism in vivo and in vitro. After NF oral gavage with mice, a total of 55 metabolites, containing 14 novel phase I metabolites and 18 novel phase II metabolites, were identified with high-resolution mass spectrometry-based metabolomics. Recombinant enzyme screenings showed that multiple cytochrome P450s, two UDP-glucuronosyltransferases (UGT1A4, UGT1A9), and several sulfotransferases (SULTs) participated in the metabolism of NF. In silico prediction and molecular docking of NF to the polymorphic enzymes (CYPs) provided additional support for the above experiments. This research details metabolic characteristics and provides an important reference basis for further application of NF.
荷叶碱（NF）是荷叶的主要成分之一，在中国已广泛应用于食品和药物制剂中。尽管荷叶碱具有广泛的生物活性，但经口灌胃给予荷叶碱后，其代谢特征仍知之甚少。本研究旨在表征其体内和体外代谢情况。给小鼠经口灌胃荷叶碱后，基于高分辨率质谱的代谢组学共鉴定出55种代谢产物，其中包括14种新的I相代谢产物和18种新的II相代谢产物。重组酶筛选表明，多种细胞色素P450、两种尿苷二磷酸葡萄糖醛酸转移酶（UGT1A4、UGT1A9）和几种磺基转移酶（SULTs）参与了荷叶碱的代谢。荷叶碱对多态性酶（CYPs）的计算机模拟预测和分子对接为上述实验提供了额外支持。本研究详细阐述了代谢特征，为荷叶碱的进一步应用提供了重要参考依据。
