{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T09:47:55Z","timestamp":1767260875736,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["0377_IBERPHENOL_6_E"],"award-info":[{"award-number":["0377_IBERPHENOL_6_E"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431E 2018\/07"],"award-info":[{"award-number":["ED431E 2018\/07"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/molecules26040787","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T20:31:51Z","timestamp":1612384311000},"page":"787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Metabolomics Insights of the Immunomodulatory Activities of Phlorizin and Phloretin on Human THP-1 Macrophages"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-3537","authenticated-orcid":false,"given":"Noelia","family":"Cambeiro-P\u00e9rez","sequence":"first","affiliation":[{"name":"Department of Analytical and Food Chemistry, Facultade de Ciencias, Universidade de Vigo, Campus da Auga, 32004 Ourense, Spain"}]},{"given":"Xiana","family":"Gonz\u00e1lez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Analytical and Food Chemistry, Facultade de Ciencias, Universidade de Vigo, Campus da Auga, 32004 Ourense, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0495-5376","authenticated-orcid":false,"given":"Carmen","family":"Gonz\u00e1lez-Barreiro","sequence":"additional","affiliation":[{"name":"Department of Analytical and Food Chemistry, Facultade de Ciencias, Universidade de Vigo, Campus da Auga, 32004 Ourense, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-5799","authenticated-orcid":false,"given":"Mar\u00eda Rosa","family":"P\u00e9rez-Gregorio","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Sciences, LAQV\/REQUIMTE, University of Porto, E-4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-0086","authenticated-orcid":false,"given":"Iva","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Sciences, LAQV\/REQUIMTE, University of Porto, E-4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9318-9732","authenticated-orcid":false,"given":"Nuno","family":"Mateus","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Sciences, LAQV\/REQUIMTE, University of Porto, E-4169-007 Porto, Portugal"}]},{"given":"Victor","family":"de Freitas","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Sciences, LAQV\/REQUIMTE, University of Porto, E-4169-007 Porto, Portugal"}]},{"given":"Borja","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Biochemistry, Dairy Research Institute of Asturias, Spanish National Research Council (IPLA-CSIC), Paseo R\u00edo Linares sn, 33300 Villaviciosa, Spain"}]},{"given":"Elena","family":"Mart\u00ednez-Carballo","sequence":"additional","affiliation":[{"name":"Department of Analytical and Food Chemistry, Facultade de Ciencias, Universidade de Vigo, Campus da Auga, 32004 Ourense, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21193","DOI":"10.3390\/molecules201219754","article-title":"Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines","volume":"20","author":"Qin","year":"2015","journal-title":"Molecules"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sut, S., Zengin, G., Maggi, F., Malagoli, M., and Dall\u2019Acqua, S. 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