Metabolomic Characterization of Phoradendron brachystachyum Mistletoe and In-Silico and In-Vitro Investigation of Its Therapeutic Potential in Metabolic Disorders

Abstract

Plants of the Phoradendron genus have been traditionally used for their lipid- and glucose-lowering effects. However, the compounds responsible for these effects and the overall chemical profile of these plants have not been thoroughly investigated. We aimed to characterize the metabolome of leaves, stems, and aerial parts of the Phoradendron brachystachyum plant. We used mass spectrometry and colorimetric screening techniques (with various solvents) to identify and characterize the metabolites present. We also evaluated the antioxidant (FRAP, ORAC, TEAC, and DPPH assays) and inhibitory effects on pancreatic lipase and α-glucosidase enzymes of hydrophilic extracts. Furthermore, we compared the molecular fingerprints between the identified metabolites and FDA-approved drugs to gain insights into the metabolites that might be responsible for the observed effects on enzymes. Our findings revealed the presence of 59 putative metabolites, primarily flavonoids. However, we also hint at the presence of peptide and carbohydrate derivatives. The leaf extracts demonstrated the most promising metrics across all assays, exhibiting strong antioxidant and enzyme inhibitory effects as well as high levels of phenolic compounds, flavonoids, and tannins. Fingerprint analysis suggested potential peptide and carbohydrate metabolites as pancreatic lipase and α-glucosidase inhibitors. Overall, our study provides evidence on specific metabolites in Phoradendron brachystachyum that could be responsible for the therapeutic effects noted in obese and type 2 diabetes subjects.