Combinatorial effects of trans-cinnamaldehyde with fluoride and chlorhexidine on Streptococcus mutans.

AIMS: The aim of this study was to investigate the effects of trans-cinnamaldehyde (TC) and its synergistic activity with chlorhexidine (CHX) and fluoride against Streptococcus mutans. METHODS AND RESULTS: Streptococcus mutans UA159 was treated with TC alone and in combination with CHX or sodium fluoride. The synergy profile was analysed using the Zero Interaction Potency model. TC showed strong synergism (synergy score of 21·697) with CHX, but additive effect (synergy score of 5·298) with fluoride. TC and the combinations were tested for acid production (glycolytic pH drop) and biofilm formation by S. mutans, and nitric oxide production in macrophages. TC significantly inhibited sucrose-dependent biofilm formation and acid production by S. mutans. Mechanistic studies were carried out by qRT-PCR-based transcriptomic studies which showed that TC acts by impairing genes related to metabolism, quorum sensing, bacteriocin expression, stress tolerance and biofilm formation. CONCLUSIONS: trans-Cinnamaldehyde potentiates CHX and sodium fluoride in inhibiting S. mutans biofilms and virulence through multiple mechanisms. This study sheds significant new light on the potential to develop TC as an anti-caries treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Oral diseases were classified as a 'silent epidemic' in the US Surgeon General's Report on Oral Health. Two decades later, >4 billion people are still affected worldwide by caries, having significant effects on the quality of life. There is an urgent need to develop novel compounds and strategies to combat dental caries. Here, we prove that TC downregulates multiple pathways and potentiates the CHX and fluoride to prevent S. mutans biofilms and virulence. This study sheds significant new light on the potential to develop TC in combination with CHX or fluoride as novel treatments to arrest dental caries.