Metabolomics Insights of the Immunomodulatory Activities of Phlorizin and Phloretin on Human THP-1 Macrophages
Noelia Cambeiro-Pérez,
Xiana González-Gómez,
Carmen González-Barreiro,
María Rosa Pérez-Gregorio,
Iva Fernandes,
Nuno Mateus,
Victor de Freitas,
Borja Sánchez,
Elena Martínez-Carballo
Affiliations
Noelia Cambeiro-Pérez
Department of Analytical and Food Chemistry, Facultade de Ciencias, Universidade de Vigo, Campus da Auga, 32004 Ourense, Spain
Xiana González-Gómez
Department of Analytical and Food Chemistry, Facultade de Ciencias, Universidade de Vigo, Campus da Auga, 32004 Ourense, Spain
Carmen González-Barreiro
Department of Analytical and Food Chemistry, Facultade de Ciencias, Universidade de Vigo, Campus da Auga, 32004 Ourense, Spain
María Rosa Pérez-Gregorio
Department of Chemistry and Biochemistry, Faculty of Sciences, LAQV/REQUIMTE, University of Porto, E-4169-007 Porto, Portugal
Iva Fernandes
Department of Chemistry and Biochemistry, Faculty of Sciences, LAQV/REQUIMTE, University of Porto, E-4169-007 Porto, Portugal
Nuno Mateus
Department of Chemistry and Biochemistry, Faculty of Sciences, LAQV/REQUIMTE, University of Porto, E-4169-007 Porto, Portugal
Victor de Freitas
Department of Chemistry and Biochemistry, Faculty of Sciences, LAQV/REQUIMTE, University of Porto, E-4169-007 Porto, Portugal
Borja Sánchez
Department of Microbiology and Biochemistry, Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Paseo Río Linares sn, 33300 Villaviciosa, Spain
Elena Martínez-Carballo
Department of Analytical and Food Chemistry, Facultade de Ciencias, Universidade de Vigo, Campus da Auga, 32004 Ourense, Spain
Dihydrochalcones, phlorizin (PZ) and its aglycone phloretin (PT), have evidenced immunomodulatory effects through several mechanisms. However, the differential metabolic signatures that lead to these properties are largely unknown. Since macrophages play an important role in the immune response, our study aimed to characterise human THP-1 macrophages under PZ and PT exposure. A multiplatform-based untargeted metabolomics approach was used to reveal metabolites associated with the anti-inflammatory mechanisms triggered by the dihydrochalcones in LPS-stimulated macrophages, for the first time. Results showed differential phenotypic response in macrophages for all treatments. Dihydrochalcone treatment in LPS-stimulated macrophages mimics the response under normal conditions, suggesting inhibition of LPS response. Antagonistic effects of dihydrochalcones against LPS was mainly observed in glycerophospholipid and sphingolipid metabolism besides promoting amino acid biosynthesis. Moreover, PT showed greater metabolic activity than PZ. Overall, the findings of this study yielded knowledge about the mechanisms of action PZ and PT at metabolic level in modulating inflammatory response in human cells.
