Nuciferine (NF) is one of the main constituents of Lotus (Nelumbo nucifera) 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.
Keywords: UPLC-ESI-Q-TOF-MS; metabolism; molecular docking; nuciferine; recombinant enzymes.