Biomaterial Database

Diosmetin alleviates S. aureus-induced mastitis by inhibiting SIRT1/GPX4 mediated ferroptosis. 2023

Lihua Zhao, and Lei Jin, and Bin Yang

Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.

OBJECTIVE 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. 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. RESULTS 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-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. CONCLUSIONS In conclusion, the data indicated that diosmetin suppressed S. aureus-induced mastitis by attenuating inflammation and ferroptosis.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008413	Mastitis	INFLAMMATION of the BREAST, or MAMMARY GLAND.
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260	Female		Females
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000079403	Ferroptosis	A form of REGULATED CELL DEATH initiated by oxidative perturbations of the intracellular microenvironment that is under constitutive control by glutathione peroxidase 4 and can be inhibited by iron chelators and lipophilic antioxidants.	Oxytosis
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013203	Staphylococcal Infections	Infections with bacteria of the genus STAPHYLOCOCCUS.	Infections, Staphylococcal,Staphylococcus aureus Infection,Staphylococcal Infection,Staphylococcus aureus Infections
D013211	Staphylococcus aureus	Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.