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

Evelyn Peñaloza,Rafael Garrett,Paula I P De Araujo,Stephan Baumgartner,Konrad Urech,Ricardo M Borges,Claudia Scherr,Carla Holandino

doi:10.3390/molecules25174006

Abstract

Fermented aqueous extracts of Viscum album 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 V. album from two host tree species (Malus domestica and Pinus sylvestris), 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 V. album 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 V. album extracts from different host trees have different clinical applications, the present work highlights the possibility of characterizing the metabolome for identification and traceability of V. album fermented aqueous extracts.

Highlights

European mistletoe (Viscum album L., Santalaceae) is a perennial, hemi-parasite evergreen flowering plant [1,2,3]
A total of 212 metabolites were annotated in the fermented aqueous extracts of V. album, 28 by their high accurate m/z values and 184 by their high accurate m/z values and MS/MS spectra (Simplified Molecular Input Line Entry System) string, and suggested compounds are available in supplementary Table S1
This study showed the potential of non-targeted metabolic profiling for the characterization of fermented aqueous extracts of V. album samples from different host trees and manufacturing processes

Summary

Introduction

European mistletoe (Viscum album L., Santalaceae) is a perennial, hemi-parasite evergreen flowering plant [1,2,3]. It grows on the branches of different host trees (e.g., Malus domestica, Pinus sylvestris, Quercus spp., etc.) using a root-like structure called sinker, which penetrates into the xylem tissue of the host tree taking up water and mineral nutrients [2]. They are morphologically distinguished according to their host trees: V. album L. ssp. Many clinical studies demonstrated the efficacy of V. album extracts as adjuvant in cancer therapy to treat different types of tumors (gastrointestinal, breast, pancreas, lungs, kidneys, etc.), resulting in better survival rate, alleviation of conventional therapy side effects and improved quality of life, with very few adverse effects [12,13]

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