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Título: | Preclinical Evaluation of the Antimicrobial-Immunomodulatory Dual Action of Xenohormetic Molecules against Haemophilus influenzae Respiratory Infection |
Autor: | Fernández-Calvet, Ariadna CSIC ORCID; Euba, Begoña CSIC ORCID ; Caballero, Lucía CSIC ; Díez-Martínez, Roberto CSIC ORCID; Menéndez, Margarita CSIC ORCID; Ortiz-de-Solorzano, Carlos; Leiva, José; Micol, Vicente; Barrajón-Catalán, Enrique; Garmendia, Juncal CSIC ORCID | Fecha de publicación: | 17-dic-2019 | Editor: | Multidisciplinary Digital Publishing Institute | Citación: | Biomolecules 9(12): 891 (2019) | Resumen: | Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammation and impaired airway immunity, providing an opportunistic platform for nontypeable <i>Haemophilus influenzae</i> (NTHi) infection. In this context, therapies targeting not only overactive inflammation without significant adverse effects, but also infection are of interest. Increasing evidence suggests that polyphenols, plant secondary metabolites with anti-inflammatory and antimicrobial properties, may be protective. Here, a <i>Cistus salviifolius</i> plant extract containing quercetin, myricetin, and punicalagin was shown to reduce NTHi viability. Analysis of these polyphenols revealed that quercetin has a bactericidal effect on NTHi, does not display synergies, and that bacteria do not seem to develop resistance. Moreover, quercetin lowered NTHi airway epithelial invasion through a mechanism likely involving inhibition of Akt phosphorylation, and reduced the expression of bacterially-induced proinflammatory markers <i>il-8</i>, <i>cxcl-1</i>, <i>il-6</i>, <i>pde4b</i>, and <i>tnfα</i>. We further tested quercetin’s effect on NTHi murine pulmonary infection, showing a moderate reduction in bacterial counts and significantly reduced expression of proinflammatory genes, compared to untreated mice. Quercetin administration during NTHi infection on a zebrafish septicemia infection model system showed a bacterial clearing effect without signs of host toxicity. In conclusion, this study highlights the therapeutic potential of the xenohormetic molecule quercetin against NTHi infection. | Versión del editor: | https://doi.org/10.3390/biom9120891 | URI: | http://hdl.handle.net/10261/197150 | DOI: | 10.3390/biom9120891 | ISSN: | 2218-273X | E-ISSN: | 2218-273X |
Aparece en las colecciones: | (IDAB) Artículos (IQF) Artículos |
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