Concentration-dependent dual effects of silibinin on kanamycin-induced cells death in Staphylococcus aureus

Silibinin has dual effects on bacteria, depending on the concentrations or living contexts. The mechanism of either action has not yet been elucidated. Present study suggests that silibinin has yinyang impacts on the growth of Staphylococcus aureus depending on doses. S. aureus treated with low concentration of silibinin (L, 6.2 μM) showed enhanced resistance to kanamycin through increased level of hydrogen peroxide (H₂O₂). However, S. aureus treated with medium concentration of silibinin (M, 50 μM) showed increased susceptibility to kanamycin through reduced level of H₂O₂. These findings suggested that dual effects of silibinin were concentration-dependent and apparently related to the levels of H₂O₂ that assist bacterial survival at higher concentrations. Interestingly, treatment with high concentration of silibinin (H, 400 μM) alone without kanamycin exhibited cytotoxicity to S. aureus regardless of H₂O₂ levels. Based on the findings in vitro, we moved to examine the influence of silibinin on S. aureus-induced mouse peritonitis model. Silibinin at high concentration was shown to enhance the survival of peritonitis mice and protected them from S. aureus-induced tissue injury presumably by antibacterial effect of high concentration of silibinin. When the infected mice were co-treated with kanamycin, bacterial burden and H₂O₂ levels in lung, liver and spleen were all increased by treatment with a low dose of silibinin, while decreased with a medium dose of silibinin. Thus, the findings highlighted the potential of silibinin to be as a modifying agent in case of antibiotic resistance.