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Chlorinated Flavonoids Modulate the Inflammatory Process in Human Blood

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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.

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Acknowledgments

This work received financial support from National funds [Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência (FCT/MEC)] and European Union funds [Fundo Europeu de Desenvolvimento Regional (FEDER)] under the program PT2020 (PT2020 UID/MULTI/04378/2013 - POCI/01/0145/FEDER/007728), the QOPNA research Unit (FCT UID/QUI/00062/2013), the framework of QREN (NORTE-01-0145-FEDER-000024), and Programa Operacional Competitividade e Internacionalização (COMPETE) (PTDC/QEQ-QAN/1742/2014–POCI-01-0145-FEDER-016530). We gratefully acknowledge Graça Porto and the nursing staff of the Centro Hospitalar do Porto–Hospital de Santo António blood bank for the collaboration in the recruitment of blood donors to participate in the study.

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Authors and Affiliations

  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

    Carina Proença, Daniela Ribeiro, Tânia Soares, Eduarda Fernandes & Marisa Freitas

  2. Department of Chemistry and QOPNA, University of Aveiro, 3810-193, Aveiro, Portugal

    Sara M. Tomé & Artur M. S. Silva

  3. LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal

    José L. F. C. Lima

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  1. Carina Proença
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  2. Daniela Ribeiro
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  3. Tânia Soares
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  4. Sara M. Tomé
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  5. Artur M. S. Silva
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  6. José L. F. C. Lima
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  7. Eduarda Fernandes
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  8. Marisa Freitas
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Correspondence to Eduarda Fernandes or Marisa Freitas.

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Proença, C., Ribeiro, D., Soares, T. et al. Chlorinated Flavonoids Modulate the Inflammatory Process in Human Blood. Inflammation 40, 1155–1165 (2017). https://doi.org/10.1007/s10753-017-0559-8

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