Comprehensive Metabolome Analysis of Fermented Aqueous Extracts of L. by Liquid Chromatography-High Resolution Tandem Mass Spectrometry.

Fermented aqueous extracts of L. are widely used for cancer treatment in complementary medicine. The high molecular weight compounds viscotoxins and lectins are considered to be the main active substances in the extracts. However, a vast number of small molecules (≤1500 Da) is also expected to be present, and few studies have investigated their identities. In this study, a comprehensive metabolome analysis of samples of fermented aqueous extracts of from two host tree species ( and ), both prepared by two pharmaceutical manufacturing processes, was performed by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). A total of 212 metabolites were putatively annotated, including primary metabolites (e.g., amino acids, organic acids, etc.) and secondary metabolites (mostly phenolic compounds). A clear separation between samples according to the host tree species, but not due to manufacturing processes, was observed by principal component analysis. The biomarkers responsible for this discrimination were assessed by partial least squares-discriminant analysis. Because extracts from different host trees have different clinical applications, the present work highlights the possibility of characterizing the metabolome for identification and traceability of fermented aqueous extracts.