Preclinical evaluation of the antimicrobial-immunomodulatory dual action of xenohormetic molecules against haemophilus influenzae respiratory infection
Keywords: 
Polyphenol
Xenohormesis
Haemophilus influenzae
Antimicrobial
Anti-inflammatory
Respiratory infection
Issue Date: 
2019
Publisher: 
MDPI AG
ISSN: 
2218-273X
Note: 
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Citation: 
Fernández-Calvet, A. (Ariadna); Euba, B. (Begoña); Caballero, L. (Lucía); et al. "Preclinical evaluation of the antimicrobial-immunomodulatory dual action of xenohormetic molecules against haemophilus influenzae respiratory infection". Biomolecules. 9 (12), 2019, 891
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammation and impaired airway immunity, providing an opportunistic platform for nontypeable Haemophilus influenzae (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 Cistus salviifolius 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 il-8, cxcl-1, il-6, pde4b, and tnfα. 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.

Files in This Item:
Thumbnail
File
biomolecules-09-00891-v2.pdf
Description
Size
1.41 MB
Format
Adobe PDF


Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.