Biocompatible combinations of nisin and licorice polyphenols exert synergistic bactericidal effects against Enterococcus faecalis and inhibit NF-κB activation in monocytes.

Enterococcus faecalis is one of the bacterial species most frequently isolated from persistent endodontic and apical periodontal infections. The aim of the present study was to evaluate the synergistic antibacterial effects of nisin and selected licorice polyphenols (glabridin, licoricidin, licochalcone A) against planktonic and biofilm-embedded E. faecalis cells. The biocompatibility and anti-inflammatory properties of the nisin/licorice polyphenol combinations were also investigated. The lantibiotic bacteriocin (nisin), the two isoflavonoids (glabridin, licoricidin), and the chalcone (licochalcone A) efficiently inhibited the growth of E. faecalis, with MICs ranging from 6.25 to 25 µg/mL. Combining nisin with each licorice polyphenol individually resulted in a significant synergistic antibacterial effect. Following a 30-min contact, nisin in combination with either glabridin, licoricidin, or licochalcone A caused significant biofilm killing. The nisin/licorice polyphenol combinations had no cytotoxic effects (oral epithelial cells, gingival fibroblasts, and stem cells of the apical papilla), with the exception of nisin/glabridin, when used at their MICs. Lastly, we showed that nisin/glabridin, nisin/licoricidin, and nisin/licochalcone A inhibit NF-κB activation induced by E. faecalis in a monocyte model, suggesting that these combinations possess anti-inflammatory properties. The present study provides evidence that combinations of nisin and glabridin, licoricidin, or licochalcone A show promise as root canal disinfection agents.

Antimicrobial activities of natural plant compounds against endodontic pathogens and biocompatibility with human gingival fibroblasts.

OBJECTIVES: The aim of the present study was to investigate three licorice-derived polyphenols (glabridin, licochalcone A, licoricidin) as well as cinnamon oil for their antimicrobial activities against major endodontic pathogens: Enterococcus faecalis, Streptococcus mutans, Actinomyces israelii, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas endodontalis, and Candida albicans. The synergistic interactions between the four compounds and chlorhexidine were assessed on E. faecalis. Lastly, the biocompatibility of the tested compounds was assessed using human gingival fibroblasts. DESIGN: Minimal inhibitory concentrations (MIC) and minimal microbicidal concentrations (MMC) were determined using a microplate dilution assay. A luminescence assay monitoring adenosine triphosphate was used to assess the antimicrobial activity of the tested compounds against E. faecalis biofilm. The synergistic effects of the tested compounds in association with chlorhexidine were evaluated using the checkerboard technique. Cytotoxicity toward human gingival fibroblasts was assessed by determination of cell metabolic activity using a colorimetric assay. RESULTS: Cinnamon oil showed the strongest microbicidal activity. Licochalcone A, licoricidin, and glabridin had MIC values ranging from 1.56 to 25 µg/mL against the six endodontic bacterial pathogens. The natural plant compounds were active to various extents against E. faecalis embedded in a biofilm. Synergistic antibacterial effects between chlorhexidine and the compounds, mainly glabridin, were observed against E. faecalis. Following a 2-h exposure, licochalcone A, licoricidin, and glabridin demonstrated no cytotoxicity toward gingival fibroblasts at concentrations up to 50 µg/mL, while cinnamon oil and, to a lesser extent, chlorhexidine displayed some cytotoxicity. CONCLUSIONS: The present study provides evidence that the natural plant compounds tested show promise as root canal disinfection agents.