Plant flavones enhance antimicrobial activity of respiratory epithelial cell secretions against Pseudomonas aeruginosa

Abstract

Flavones are a class of natural plant secondary metabolites that have anti-inflammatory and anti-bacterial effects. Some flavones also activate the T2R14 bitter taste receptor, which is expressed in motile cilia of the sinonasal epithelium and activates innate immune nitric oxide (NO) production. Flavones may thus be potential therapeutics for respiratory infections. Our objective was to examine the anti-microbial effects of flavones on the common sinonasal pathogens Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa, evaluating both planktonic and biofilm growth. Flavones had only very low-level antibacterial activity alone. They did not reduce biofilm formation, but did reduce production of the important P. aeruginosa inflammatory mediator and ciliotoxin pyocyanin. However, flavones exhibited synergy against P. aeruginosa in the presence of antibiotics or recombinant human lysozyme. They also enhanced the efficacy of antimicrobials secreted by cultured and primary human airway cells grown at air-liquid interface. This suggests that flavones may have anti-gram-negative potential as topical therapeutics when combined with antibiotics or in the context of innate antimicrobials secreted by the respiratory or other epithelia. This may have an additive effect when combined with T2R14-activated NO production. Additional studies are necessary to understand which flavone compounds or mixtures are the most efficacious.

Broncho‐Vaxom® (OM‐85 BV) soluble components stimulate sinonasal innate immunity

“…Prior studies of sinonasal immunity have demonstrated a T2R‐mediated mechanism for increases in CBF and other local immune defenses such as the release of NO and secretion of antimicrobial compounds . It is known that T2R activation by secreted bacterial products as well as other biologically active compounds results in NO production, which is not only directly bactericidal but also increases CBF. To determine whether the topical application of bacterial lysate may work by a similar mechanism of action, ALIs were pretreated with either a NOS inhibitor or inhibitors of bitter taste‐receptor signal transduction.…”

“…Recent research has provided support for the role of taste receptors in the sinonasal epithelium to sense their environment and initiate local immune defenses including mucociliary clearance and antimicrobial product release . These taste receptors are known to be activated by secreted bacterial products, and other compounds with biological activity are continuously being discovered . Given this emerging role of the sinonasal epithelium in the regulation of upper airway immunity, the nasal delivery of topical agents that augment the natural host response is an attractive therapeutic option in the treatment of rhinosinusitis and other local disease.…”

Inverse regulation of secretion and inflammation in human airway gland serous cells by neuropeptides upregulated in allergy and asthma

“…ASL height and pH measurements and ELISAs were carried out as previously reported (92,129,(151)(152)(153)(154)(155)(156)(157). Bacterial growth assays were carried out as previously described (158,159). More detailed methods for all procedures as well as specific reagents used are provided in the Supplemental Materials.…”

<b><i>Panax Notoginseng</i></b> Extract Possesses Significant Antibacterial Activity against Pathogenic Streptococci

“…Panax notoginseng contains more than 200 metabolites, including saponins and flavonoids, each of which has been reported to have various pharmacological effects [7,8]. Several saponins and flavonoids have been shown to have both direct and indirect antimicrobial activities [10][11][12]. Therefore, although the main purpose of PNE is not the treatment of infections, this extract may indeed have antimicrobial effects.…”