Abstract

Simple Summary Mastitis is a common disease in dairy cows that causes inflammation of the mammary gland, reduces milk production and quality, and may increase the need for antibiotics. This creates economic losses and raises concerns about antibiotic residues and drug resistance. The aim of this study was to determine whether Forsythiaside A, a natural compound from Forsythia suspensa, could protect mammary cells and tissues from damage caused by bacterial toxin exposure. We used mammary epithelial cells and a mouse model of mastitis to evaluate inflammation, oxidative damage, mitochondrial injury, and iron-related cell damage called ferroptosis. The results showed that bacterial toxin caused clear inflammatory injury and ferroptosis-like damage, while Forsythiaside A reduced inflammation, lowered harmful oxidative products, improved antioxidant defenses, and protected mitochondrial function and mammary tissue structure. Further experiments showed that these protective effects were related to activation of an internal cellular defense pathway that helps maintain redox balance and prevent iron-related cell damage. These findings suggest that Forsythiaside A may be a useful natural candidate for reducing mastitis-related mammary injury and could support the development of safer, non-antibiotic strategies for improving dairy animal health.