Metabolic profiling of myrislignan by UPLC-ESI-QTOFMS-based metabolomics

Myrislignan (MRL) is a bioactive 8-O-4'-neolignan distributed in nutmeg that is an official Traditional Chinese Medicine used for the treatment of gastrointestinal diseases in China. In the present study, the metabolic map of MRL was determined in mouse by ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics. A total of 23 MRL metabolites (19 were newly identified) were determined in both in vivo and in vitro metabolism of MRL. It was found that hydroxylation and demethylation were the major metabolic pathways for MRL metabolism in vitro and in vivo, respectively. Recombinant cytochrome P450s (CYPs) screening revealed that CYP3A4 and CYP3A5 played a crucial role in the metabolism of MRL. Interestingly, MRL and its metabolites were prone to generate the high abundance ions of Na+ adducts due to one 8-O-4' type bond in their molecular structures. Taken together, these data reveal the metabolic map of MRL, contributing to the understanding of the metabolism and disposition of 8-O-4'-neolignans in nutmeg.Thousand Young Talents Program of China; National Natural Science Foundation of China [81360509]; State Key Laboratory of Phytochemistry and Plant Resources in West China [52Y67A9211Z1]; Ministry of Human Resources and Social Security of Yunnan Province, China [39Y732921261]SCI(E)ARTICLE6440131-40140