title: Chlorinated Flavonoids Modulate the Inflammatory Process in Human Blood.
abstract: Flavonoids are known to react with neutrophil-generated hypochlorous acid (HOCl) at inflammation loci to form stable mono- and dichlorinated products. Some of these products have been shown to retain or even enhance their inflammatory potential, but further information is required in a broader approach to inflammatory mechanisms. In that sense, we performed an integrated evaluation on the anti-inflammatory potential of a panel of novel chlorinated flavonoids and their parent compounds, in several steps of the complex inflammatory cascade, namely, in the activity of cyclooxygenase (COX)-1 and COX-2, and in the production of cytokines [interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)], and the chemokine, IL-8, as well as in the production of reactive species, using human whole blood as a representative in vitro model, establishing, whenever possible, a structure-activity relationship. Although luteolin was the most active compound, chlorinated flavonoids demonstrated a remarkable pattern of activity for the resolution of the inflammatory processes. Our results demonstrated that 6-chloro-3',4',5,7-tetrahydroxyflavone deserves scientific attention due to its ability to modulate the reactive species and cytokines/chemokine production. In this regard, the therapeutic potential of flavonoids' metabolites, and in this particular case the chlorinated flavonoids, should not be neglected.
authors.affiliation: UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
authors.forename: Carina
authors.initials: C
authors.lastname: Proença
authors.affiliation: UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ribeiro
authors.affiliation: UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Soares
authors.affiliation: Department of Chemistry and QOPNA, University of Aveiro, 3810-193, Aveiro, Portugal.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Tomé
authors.affiliation: Department of Chemistry and QOPNA, University of Aveiro, 3810-193, Aveiro, Portugal.
authors.forename: Artur M S
authors.initials: AMS
authors.lastname: Silva
authors.affiliation: LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.
authors.forename: José L F C
authors.initials: JLFC
authors.lastname: Lima
authors.affiliation: UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal. egracas@ff.up.pt.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
authors.affiliation: UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal. marisafreitas@ff.up.pt.
authors.forename: Marisa
authors.initials: M
authors.lastname: Freitas
mesh_terms: D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006843:Hydrocarbons, Chlorinated; D006997:Hypochlorous Acid / Q000737:chemistry*; D007249:Inflammation / Q000097:blood*; D018836:Inflammation Mediators / Q000737:chemistry / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D016207:Cytokines; D005419:Flavonoids; D006843:Hydrocarbons, Chlorinated; D018836:Inflammation Mediators; D016209:Interleukin-8; D006997:Hypochlorous Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: anti-inflammatory effect; chemokines; cyclooxygenase; cytokines; human whole blood; reactive oxygen species