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Metabolite identification, in the early stage, for compound discovery is necessary to assess the knowledge for the pharmaceutical improvement of drug safety and efficacy. Even if the drug has been released into the market, identification and continuous evaluation of the metabolites are required to avoid the risk of post-marketing withdrawal. Hericium erinaceus (HE), a medicinal mushroom, has broadly documented nutraceutical benefits, including anti-oxidant, anti-tumor, anti-aging, hypolipidemic, and gastric mucosal protection effects. Recently, erinacine A has been reported as the main natural bioactive compound in the mycelium of HE for functional food development. In neurological studies, the consumption of enrinacine A enriched HE mycelium demonstrates its significant nutraceutical effects in Alzheimer’s disease, Parkinson’s disease, and ischemic stroke. For the first time, we explored the metabolic process of erinacine A molecule and identified its metabolites from the rat and human liver S9 fraction. Using a liquid chromatography/triple quadrupole mass spectrometer for quantitative analysis, we observed that 75.44% of erinacine A was metabolized within 60 min in rat, and 32.34% of erinacine A was metabolized within 120 min in human S9. Using an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to identify the metabolites of erinacine A, five common metabolites were identified, and their possible structures were evaluated. Understanding the metabolic process of erinacine A and establishing its metabolite profile database will help promote the nutraceutical application and discovery of related biomarkers in the future.

Identification of Common Liver Metabolites of the Natural Bioactive Compound Erinacine A, Purified from Hericium erinaceus Mycelium