Abstract
Dental caries is a prevalent biofilm-related oral infectious disease, in which Streptococcus mutans plays an important role in the pathological process. The discovery of novel agents with inhibitory effects on S. mutans is essential to develop effective strategies against dental caries. Plant extracts are a rich source of novel chemicals for the discovery of more effective antimicrobial agents. Coptis chinensis Franch. is a traditional Chinese herbal medicine with various pharmacological properties. This study aimed to evaluate the antimicrobial activity of berberine (BBR), a bioactive alkaloid isolated from Coptis chinensis Franch., on the biofilm formation of S. mutans and to investigate the relevant mechanism of its action. The study found that BBR inhibited the growth of planktonic S. mutans, as demonstrated by Minimum Inhibitory Concentration, Minimum Bactericidal Concentration, and growth curve assay. BBR was found to inhibit biofilm formation and exhibit antimicrobial effects on S. mutans, as demonstrated by crystal violet staining assay, confocal laser scanning microscopy, and CFU counting assay. Moreover, the inhibitory effect of BBR on the virulence of S. mutans was evaluated by the anthrone-sulfuric method and lactic acid assay. Bacterial aggregation assay, membrane potential assay, and transmission electron microscopy were used to preliminarily elucidate the membrane-destructive bactericidal mechanism of BBR. The expression of virulence genes gtfB, gtfC, gtfD, ldh, vicR, liaR, and comD was measured using quantitative real-time PCR (qRT-PCR). The cell viability assay on human oral cells and macrophages demonstrated that BBR exhibited no cytotoxicity to the tested host cells. In conclusion, the study demonstrates that BBR has significant anticaries activity against S. mutans and has the potential to be further developed as a novel anticaries agent for clinical use.IMPORTANCEDental caries is a chronic disease affecting people worldwide, which could cause a series of oral problems. Plant-derived compounds have shown antimicrobial properties against a wide range of pathogens. This study investigated the antimicrobial effect of BBR on Streptococcus mutans, including the inhibitory effect on the planktonic bacteria growth, biofilm formation, virulence factors, and explored the mechanism and biocompatibility of BBR. This study demonstrated the significant anticaries activity of BBR against S. mutans and its potential to be further developed as a novel anticaries agent for clinical prevention and treatment of dental caries.