Synergistic Antibacterial Effect of Lactic Acid Bacteria and Baicalin Against <i>Staphylococcus aureus In Vitro</i> and <i>In Vivo</i>

Pathogenic bacteria such as <i>Staphylococcus aureus</i> (<i>S. aureus</i>) are the principal cause of cow mastitis, which primarily impacts milk yield and results in significant financial losses for the animal husbandry industry. Lactic acid bacteria-cell-free supernatant (LAB-CFS) and baicalin (BAI) both have a number of biological effects, including decreasing inflammation. The combined use of LAB-CFS and BAI does not appear to have been used to protective against mastitis, however, and the underlying mechanisms are yet unknown. In this study, <i>in vitro</i> activity of LAB-CFS and BAI alone and in combination was determined (checkerboard experiments, time-kill curves, and flow cytometry to investigate membrane permeability) and examined the protective effects of LAB-CFS and BAI on <i>S. aureus</i>-induced mastitis in mice and the impact of NF-κB signaling pathways on the emergence of mastitis. We discovered that when LAB-CFS and BAI were used together, <i>S. aureus</i> was more effectively treated than when LAB-CFS and BAI were used separately. Flow cytometry demonstrated that LAB-CFS and BAI work together to kill bacteria. <i>In vivo</i>, the usage of LAB-CFS and BAI decreased the activity of myeloperoxidase, as well as IL-6, IL-1β, and TNF-α secretion and the levels of TLR2 and p65 (NF-κB) expression. These findings suggested that LAB-CFS and BAI had a preventive effect against mastitis brought on by <i>S. aureus</i>. Therefore, the NF-κB signaling pathway is thought to be the likely mechanism through which LAB-CFS and BAI reduced <i>S. aureus</i>-induced inflammation in the mammary of cows. For the treatment of cow mastitis, LAB-CFS and BAI are likely to replace antibiotics.