Chlorinated Flavonoids Modulate the Inflammatory Process in Human Blood
- PDF / 965,101 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 75 Downloads / 195 Views
ORIGINAL ARTICLE
Chlorinated Flavonoids Modulate the Inflammatory Process in Human Blood Carina Proença,1 Daniela Ribeiro,1 Tânia Soares,1 Sara M. Tomé,2 Artur M. S. Silva,2 José L. F. C. Lima,3 Eduarda Fernandes,1,4 and Marisa Freitas1,4
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 6chloro-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. KEY WORDS: anti-inflammatory effect; human whole blood; cyclooxygenase; cytokines; chemokines; reactive oxygen species.
INTRODUCTION Inflammation is a pathophysiological process that it is engaged by both innate and adaptive immune systems to combat pathogenic intruders [1, 2]. An uncontrolled and/or prolonged inflammatory process is associated with the 1
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 2 Department of Chemistry and QOPNA, University of Aveiro, 3810193 Aveiro, Portugal 3 LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050313 Porto, Portugal 4 To whom correspondence should be addressed at 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. E-mails: [email protected]; [email protected]
genesis of chronic diseases. It has been calculated that, in 2001, chronic diseases, comprising directly and indirectly related inflammatory diseases, contributed approximately 60% for the 56.5 million total reported deaths in the world [3]. Due to the critical etiology and complexity of inflammatory processes and their intrinsic mechanism
Data Loading...
