Abstract— Although a broad range of biological and pharmacological activities of apigenin have been reported, the mechanism(s) behind its antibacterial effects are not fully understood. In this study, we investigated the synergistic antibacterial activity of apigenin in combination with existing antimicrobial agents against oral bacteria. The combination effect of apigenin was evaluated against oral bacteria, either alone or with antibiotics, via broth dilution method and checkerboard and time kill assay. MIC/MBC values for apigenin, ampicillin, gentamicin, erythromycin, and vancomycin against all the tested bacteria ranged between 50-200/100-800 microg/mL, 0.0313-16/0.125-32 microg/mL, 2-256/4-512 microg/mL, 0.008-32/0.016-64 microg/mL, and 0.25-64/1-128 microg/mL, respectively. Checkerboard assay revealed synergistic activity in the combination of apigenin with antibiotics at fractional inhibitory concentration index (FICI) <0.5. 1-6 hours of treatment with 1/2 MIC of apigenin with 1/2 MIC of antibiotics resulted from an increase of the rate of killing in units of CFU/mL to a greater degree than was observed with alone. These results suggest that the apigenin is important in the antibacterial actions of oral pathogen agents.
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