title: Effects of naringenin and its phase II metabolites on in vitro human macrophage gene expression.
abstract: Naringenin, together with its glycosidic forms, is a flavanone abundant in grapefruit and orange. It has been detected in human plasma, following citrus juice intake, at sub-µmolar concentrations, and its main phase II conjugated metabolites (naringenin-7-O-glucuronide and narigenin-4'-O-glucuronide) have been identified in urine. Recent evidence suggests a potential active anti-inflammatory role of flavonoids on macrophages, cells actively involved in atherogenesis. The aim of this study was to evaluate the effects of naringenin and its phase II metabolites on the expression of specific genes in differently activated macrophages at concentrations coherent with dietary exposure. Results suggest that phase II metabolites, as well as the aglyconic form of naringenin, were able to perturb macrophage gene expression in directions that are not always consistent with anti-inflammatory effects. Moreover, the effects of metabolites were not always consistent with each other and with those of their aglycone, underlining the paramount importance of testing physiological forms of phytochemicals within in vitro experimental models. In vivo studies are needed to further explore these observations and investigate their practical consequences.
authors.affiliation: The φ2 Laboratory of Phytochemicals in Physiology, Department of Food Science, University of Parma , Parma , Italy .
authors.forename: Margherita
authors.initials: M
authors.lastname: Dall'Asta
authors.forename: Eleonora
authors.initials: E
authors.lastname: Derlindati
authors.forename: Valentina
authors.initials: V
authors.lastname: Curella
authors.forename: Pedro
authors.initials: P
authors.lastname: Mena
authors.forename: Luca
authors.initials: L
authors.lastname: Calani
authors.forename: Sumantra
authors.initials: S
authors.lastname: Ray
authors.forename: Ivana
authors.initials: I
authors.lastname: Zavaroni
authors.forename: Furio
authors.initials: F
authors.lastname: Brighenti
authors.forename: Daniele
authors.initials: D
authors.lastname: Del Rio
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D050197:Atherosclerosis; D018929:Cell Culture Techniques; D002957:Citrus / Q000737:chemistry*; D004032:Diet; D044950:Flavanones / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D050217:Metabolic Detoxication, Phase II; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D044950:Flavanones; D010936:Plant Extracts; C005273:naringenin