Journal
LIFE SCIENCES
Volume 331, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2023.122060
Keywords
S. aureus; Diosmetin; NF-kappa B; Mastitis; Ferroptosis
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The study found that diosmetin suppressed Staphylococcus aureus-induced mastitis by attenuating inflammation and ferroptosis.
Aims: Microbial 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 methods: The 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 findings: Our 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-alpha and IL-1 beta, and nuclear factor kappa-B (NF-kappa B) 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. Significance: In conclusion, the data indicated that diosmetin suppressed S. aureus-induced mastitis by attenuating inflammation and ferroptosis.
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