Artemisinins inhibited the synergistic cariogenic effect between Candida albicans and Streptococcus mutans.

BACKGROUND: Dental caries, a globally prevalent disease, burdens health and economies. Targeting Candida albicans-Streptococcus mutans synergism aids managing severe early childhood caries and root caries. Artemisinin, a natural antimalarial, inhibits C. albicans virulence via hyphal and biofilm suppression, promising to disrupt this cross-kingdom cariogenic partnership. OBJECTIVE: This study evaluated the inhibitory effects of seven common artemisinin compounds on the synergistic cariogenic effect of C. albicans-S. mutans biofilm, in order to expand the application of artemisinin compounds in the field of caries prevention. METHODS: Hyphal induction, biofilm formation, and CFU assays evaluated the inhibitory efficacy of the compounds against C. albicans and S. mutans. RT-qPCR examinations analyzed the expression of key virulence genes in both species. The anti-caries efficacy of artemisinin compounds was further validated in a rat caries model, demonstrated by quantitative analysis of microbial load in dental plaque and Keyes scoring for molar carious lesions. RESULTS: All seven artemisinin derivatives effectively inhibited hyphal formation in C. albicans. Artemisinic acid and dihydroartemisinic acid additionally exhibited direct antibacterial activity against S. mutans, significantly suppressing dual-species biofilm formation, EPS synthesis, and acid production. All compounds downregulated key virulence genes in both pathogens. In vivo studies confirmed that artemisinic acid and dihydroartemisinic acid reduced microbial colonization and caries severity, while other derivatives primarily exerted anticaries effects by inhibiting C. albicans colonization. CONCLUSION: Artemisinin compounds can reduce the synergistic cariogenic virulence of C. albicans and S. mutans by inhibiting the interaction between C. albicans and S. mutans.