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.

Keywords: Biofilm; Enterococcus faecalis; Licorice; Monocytes; NF-κB; Nisin; Polyphenols; Synergy.