Cyanidin-3-O-glucoside mitigates Staphylococcus aureus-induced mastitis by suppressing inflammatory responses and...

Mastitis is a significant concern in both human and animal medicine. The causative agent S. aureus is one of the most challenging pathogens responsible for mastitis, and the rise of its antibiotic resistance underscores the need for alternative therapies. The SESN2/Nrf2 pathway, owing to its pivotal role in regulating cellular antioxidant defenses, which are critically disrupted during ferroptosis, has recently received less attention. However, whether C3G targets the SESN2/Nrf2 pathway remains unclear, which provides a dual mechanism for treating S. aureus-induced mastitis by reducing inflammation and safeguarding mammary epithelial cells (MECs) from ferroptosis. Using a mouse mastitis and MECs model, we investigated the therapeutic potential of C3G in alleviating S. aureus-induced mastitis, focusing specifically on its role in inhibiting inflammation and modulating ferroptosis through the SESN2/Nrf2 pathway. The results demonstrated the potential antimicrobial effects of C3G against S. aureus and MRSA, suppressed inflammatory responses by downregulating pro-inflammatory markers (IL-1β, IL-6, and TNF-α), and inhibited STAT2/STAT3 signaling. Furthermore, C3G modulates ferroptosis by activating the SESN2/Nrf2 pathway, reducing oxidative stress, and protecting mammary epithelial cells from ferroptosis-induced damage. This comprehensive approach highlights C3G's potential as a novel therapeutic strategy for managing mastitis, offering an effective alternative to antibiotics in addressing both bacterial infection and inflammation.