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Dental caries arises from dysbiosis of the oral microbiome, wherein acidogenic pathogens such as Streptococcus mutans dominate over protective commensals. Sodium fluoride (NaF) remains a cornerstone in caries prevention; however, its limited efficacy in high-risk individuals and the emergence of fluoride-resistant strains highlight the need for enhanced therapeutic strategies. The present study investigates the synergistic antibacterial potential of NaF combined with ricinoleic acid (RA), a bioactive fatty acid with established antimicrobial activity. Checkerboard and time-kill assays revealed a strong synergistic interaction between RA and NaF, with a combinatorial minimum inhibitory concentration (CMIC) of 64 + 128 μg/mL, respectively. Complete eradication of S. mutans was achieved within 120 min at CMIC (64 + 128 μg/mL). The combination significantly disrupted mature biofilms, resulting in an 82% reduction in total biomass as confirmed by confocal microscopy. Mechanistic analyses indicated that RA triggered reactive oxygen species (ROS) generation and membrane perturbation, which facilitated enhanced NaF uptake and intracellular antibacterial action. Moreover, the RA-NaF combination markedly inhibited key virulence attributes of S. mutans, including acidogenesis and aciduricity, by approximately 76% and 71%, respectively. The treatment also exhibited a sustained post-antimicrobial effect lasting up to 12 h and did not induce bacterial resistance upon repeated exposure. Collectively, these findings highlight that RA potentiates the anticariogenic efficacy of NaF through a multi-targeted cellular mechanism involving oxidative stress induction, membrane disruption, and metabolic suppression. This synergistic combination represents a promising and fluoride-efficient strategy for the prevention and management of dental caries.
Sangavi et al. (Mon,) studied this question.