Combinatorial treatment of sophoraflavanone G and rhein with ampicillin, oxacillin, or oxytetracycline synergistically increased antibacterial activity against oral bacteria

Various antibacterial agents have been developed to prevent dental diseases but many oral bacteria have been come out with resistance. In this study, antibacterial activities of sophoraflavanone G and rhein were investigated against oral bacteria using the microdilution assay, the checkerboard assay, the growth curve assay, and the disc diffusion assay. Minimum inhibitory concentration(MIC) values of sophoraflavanone G were 1.56 μg/ml against Streptococcus mutans and Fusobacterium nucleatum, 3.125 μg/ml against Streptococcus sobrinus and Actinomyces viscosus, and more than 100 μg/ml against Porphyromonas gingivalis after 24 h treatment, respectively. MIC values of rhein were 100 μg/ml against Strep. mutans and Strep. sobrinus, and 25 μg/ml against A. viscosus, F. nucleatum and Porphyromonas gingivalis after 24 h treatment, respectively. As both of the compounds showed antibacterial activity, combined treatment was accomplished to know synergistic activity between sophoraflavanone G and rhein, and with commercially available antibacterial agents, such as ampicillin, oxacillin, and oxytetracycline. Sophoraflavanone G with rhein showed synergistic antibacterial activity [fractional inhibitory concentration index (FICI) < 0.5] against all tested oral bacteria. Sophoraflavanone G with antibiotics usually showed additive antibacterial activity (0.5 < FICI < 1.0) but interestingly sophoraflavanone G showed strong synergistic activity with ampicillin, which showed resistance against all tested strains, and with oxacillin, which showed resistance against Strep. mutans, and Strep. sobrinus. Even though rhein possessed low antibacterial activity, it showed synergistic activity with ampicillin and oxacillin against drug-resistant strain. These results suggest that sophoraflavanone G and rhein combined with other antibacterial agents may be beneficial and provide the better option to treat the oral bacteria.