Synergistic effect between cryptotanshinone and antibiotics in oral pathogenic bacteria

Cryptotanshinone (CT), a major tanshinone of medicinal plant Salvia miltiorrhiza Bunge, demonstrated effective in vitro antibacterial activity against all oral bacteria tested in this experiment. The antibacterial activities of CT against oral bacteria were assessed using the checkerboard and time-kill methods to evaluate the synergistic effects of treatment with ampicillin or gentamicin. The CT was determined against oral pathogenic bacteria with MIC and MBC values ranging from 0.5 to 16 and 1 to 64 μg/mL; for am- picillin from 0.0313 to 16 and 0.125 to 32 μg/mL; for gentamicin from 2 to 256 and 4 to 512 μg/mL respectively. The range of MIC50 and MIC90 were 0.0625 - 8 μg/mL and 1 - 64 μg/mL, respectively. The combination effects of CT with antibiotics were synergistic (FIC index < 0.5) against tested oral bacteria except additive, Streptococcus sobrinus, S. criceti, and Actinobacillus actinomycetemcomitans (FIC index < 0.75 - 1.0). The MBCs were shown reducing ≥4 - 8-fold, indicating a synergistic effect as defined by a FBCI of ≤0.5. Furthermore, a time-kill study showed that the growth of the tested bacteria was completely attenuated after 3 - 6 h of treatment with the 1/2 MIC of CT, regardless of whether it was administered alone or with ampicillin or gentamicin. The results suggest that CT could be employed as a natural antibacterial agent against cariogenic and periodontopathogenic bac- teria.