Gardenoside attenuates Staphylococcus aureus-induced mastitis by inhibiting inflammation and ferroptosis through Nrf2/SLC7A11/GPX4 signaling pathway

The occurrence of mastitis is mainly due to the infection of mammary tissue by pathogens, which causes the inflammation of mammary tissue. Gardenoside (GAD), an iridoid active ingredient extracted from Gardenia Jasminoides Ellis, has been revealed to exhibit anti-inflammatory and anti-oxidative roles. However, the therapeutic effect of GAD on mastitis remains unclear. Our aim was to identify the therapeutic effect of GAD on Staphylococcus aureus (S. aureus)-induced mastitis and clarify its mechanism. To carry out this work, S. aureus-induced mastitis of mice model was established. Enzyme-Linked Immunosorbent Assay (ELISA) was conducted to detect the production of Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The biochemical method was used to detect the antioxidant factors glutathione (GSH), malondialdehyde (MDA), and iron content. Western blot was used to detect the expression of Nrf2/SLC7A11/GPX4 signal-related proteins. The results demonstrated that GAD alleviated Myeloperoxidase (MPO) activity, IL-1β and TNF-α production, and NF-κB activation. MDA and iron contents were also inhibited by GAD. Meanwhile, GSH level and GPX4, SLC7A11, and ferritin expressions were increased by GAD treatment. In addition, the expressions of Nrf2 and HO-1 were upregulated by GAD. In conclusion, GAP may inhibit S. aureus-induced mastitis in mice by triggering the Nrf2/SLC7A11/GPX4 signaling pathway and alleviating inflammation and ferroptosis.

Importance: Mastitis, as an important disease that endangers the development of the dairy industry, causes huge economic losses to the breeding industry. Staphylococcus aureus is one of the important pathogenic bacteria that cause mastitis. Antibiotics are considered to be the first choice in the treatment of the S. aureus-induced mastitis. However, the overuse of antibiotics leads to bacterial resistance and antibiotic residues. Therefore, this study explored whether effective extracts of traditional herbs could be used as alternatives to antibiotics.