Matrine and baicalin inhibit apoptosis induced by Panton-Valentine leukocidin of Staphylococcus aureus in bovine mammary epithelial cells

ABSTRACT It was previously thought that the Panton-Valentine leukocidin (PVL) toxin of Staphylococcus aureus (S. aureus) was not the main cause of cow mastitis. However, in recent years, detection of the gene encoding PVL has been increasing in dairy cow mastitis, which implies that PVL may be related to bovine mastitis. Therefore, we wanted to search for drugs inhibiting PVL or PVL-induced apoptosis. In this report, we investigated the apoptosis mechanism of PVL in bovine mammary epithelial cells (BMEC) and the inhibition mechanism of matrine and baicalin on PVL-induced apoptosis of BMEC. The results demonstrated that BMEC were damaged and underwent apoptosis by a standard PVL-producing strain of S. aureus (ATCC 49775), a PVL knockout mutant Δpvl 49775, complemented mutant C-Δpvl 49775, or recombinant (r)PVL in vitro. The rates of apoptosis and necrosis induced by S. aureus ATCC 49775 and C-Δpvl 49775 were significantly higher than those induced by Δpvl 49775, demonstrating that BMEC apoptosis and necrosis were associated with PVL. In addition, this research found matrine and baicalin could inhibit the apoptosis of BMEC induced by PVL-producing S. aureus and by rPVL. Matrine downregulated protein expression levels of endogenous and exogenous cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9, and the effect was pronounced at a concentration of 50 μg/mL. Baicalin downregulated the expression of cleaved caspase-9. These results suggested that matrine and baicalin may have potential value against cow mastitis caused by the toxin PVL.