Abstract
AimsMicrobial infection is the main factor that induces mastitis. Staphylococcus aureus (S. aureus) is a major pathogen associated with mastitis. The purpose of this study was to investigate the effects of diosmetin on S. aureus-induced mastitis. Materials and methodsThe mice were divided into six groups: control group, S. aureus group, diosmetin (12.5, 25, 50 mg/kg) + S. aureus groups, and diosmetin (50 mg/kg) + S. aureus + EX-527 (10 mg/kg) group. S. aureus was injected into the mammary gland to establish a mouse mastitis model. Diosmetin was administered 1 h before S. aureus treatment. Key findingsOur results showed that diosmetin significantly alleviated the pathological changes of mammary gland induced by S. aureus. Diosmetin alleviated myeloperoxidase (MPO) activity, and the release of TNF-α and IL-1β, and nuclear factor kappa-B (NF-κB) activation. Moreover, diosmetin inhibited malondialdehyde (MDA) and Fe2+ levels induced by S. aureus. Diosmetin upregulated ATP, glutathione (GSH) production and glutathione peroxidase 4 (GPX4) expression, which were decreased by S. aureus. Furthermore, the expression of Sirtuin 1 (SIRT1), nuclear factor erythroid2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) was upregulated by diosmetin. In addition, the inhibitory effects of diosmetin on S. aureus-induced inflammation and ferroptosis were prevented by the SIRT1 inhibitor EX-527. SignificanceIn conclusion, the data indicated that diosmetin suppressed S. aureus-induced mastitis by attenuating inflammation and ferroptosis.
Published Version
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