Dual action of highbush blueberry proanthocyanidins on Aggregatibacter actinomycetemcomitans and the host inflammatory response

Abstract

BackgroundThe highbush blueberry (Vaccinium corymbosum) has a beneficial effect on several aspects of human health. The present study investigated the effects of highbush blueberry proanthocyanidins (PACs) on the virulence properties of Aggregatibacter actinomycetemcomitans and macrophage-associated inflammatory responses.MethodsPACs were isolated from frozen highbush blueberries using solid-phase chromatography. A microplate dilution assay was performed to determine the effect of highbush blueberry PACs on A. actinomycetemcomitans growth as well as biofilm formation stained with crystal violet. Tight junction integrity of oral keratinocytes was assessed by measuring the transepithelial electrical resistance (TER), while macrophage viability was determined with a colorimetric MTT assay. Pro-inflammatory cytokine and MMP secretion by A. actinomycetemcomitans-stimulated macrophages was quantified by ELISA. The U937-3xκB-LUC monocyte cell line transfected with a luciferase reporter gene was used to monitor NF-κB activation.ResultsHighbush blueberry PACs reduced the growth of A. actinomycetemcomitans and prevented biofilm formation at sub-inhibitory concentrations. The treatment of pre-formed biofilms with the PACs resulted in a loss of bacterial viability. The antibacterial activity of the PACs appeared to involve damage to the bacterial cell membrane. The PACs protected the oral keratinocytes barrier integrity from damage caused by A. actinomycetemcomitans. The PACs also protected macrophages from the deleterious effect of leukotoxin Ltx-A and dose-dependently inhibited the secretion of pro-inflammatory cytokines (IL-1β, IL-6, CXCL8, TNF-α), matrix metalloproteinases (MMP-3, MMP-9), and sTREM-1 by A. actinomycetemcomitans-treated macrophages. The PACs also inhibited the activation of the NF-κB signaling pathway.ConclusionThe antibacterial and anti-inflammatory properties of highbush blueberry PACs as well as their ability to protect the oral keratinocyte barrier and neutralize leukotoxin activity suggest that they may be promising candidates as novel therapeutic agents.

Tart cherry (Prunus cerasus L.) fractions inhibit biofilm formation and adherence properties of oral pathogens and enhance oral epithelial barrier function

“…The oral mucosal epithelium plays an important barrier function against microbial infection and invasion. Recently, we reported the ability of tea polyphenols, including epigallocatechin‐3‐gallate and theaflavins, to enhance the integrity of the oral epithelial barrier (Ben Lagha, LeBel, & Grenier, ; Ben Lagha & Grenier, ). In this study, using an oral epithelial cell model, the NDM‐TCP was found to rapidly increase TER values that reflect tight junction integrity.…”

“…The oral mucosal epithelium plays an important barrier function against microbial infection and invasion. Recently, we reported the ability of tea polyphenols, including epigallocatechin-3-gallate and theaflavins, to enhance the integrity of the oral epithelial barrier (Ben Lagha, LeBel, & Grenier, 2018;Ben Lagha & Grenier, 2017).…”

Molecular Mechanism and Health Role of Functional Ingredients in Blueberry for Chronic Disease in Human Beings

“…Wild blueberry consumption has an overall anti-inflammatory effect in the metabolic syndrome [ 76 ]. The antibacterial and anti-inflammatory effects protect the oral keratinocyte barrier as well as neutralize leukotoxin properties of blueberry proanthocyanidins which could be promising candidates as novel therapeutic agents [ 45 ].…”

Synthesis and anti‐inflammatory activity of diversified heterocyclic systems

“…In the present study, we used the U937-3xκB-LUC human monocytic cell line, which contains a luciferase reporter possessing three NF-κB-binding sites, to evaluate the ability of the designed molecules to inhibit activation of the NF-κB signaling pathway. This model is very convenient to rapidly evaluate the potential of new compounds to block activation of the transcription factor NF-κB, an important regulator of many pro-inflammatory pathways (Cardinal et al, 2017;Lagha & Grenier, 2016;Lagha, LeBel, & Grenier, 2018). First, to exclude the possibility that cell toxicity might have been responsible for any decrease in NF-κB activation, the viability of the U937-3xκB-LUC cells treated with the molecules was evaluated using an MTT test.…”