Forsythiaside A Alleviates LPS-Induced Mastitis by Inhibiting Ferroptosis and Oxidative Stress

Mastitis is one of the most prevalent diseases in dairy cows, leading to significant economic losses and increased antibiotic usage. The development of safe and effective alternatives is therefore urgently needed. In this study, we investigated the protective effects of Forsythiaside A (FTA), a natural compound, against LPS-induced mastitis in bovine mammary epithelial (MAC-T) cells and a murine model. FTA significantly reduced intracellular reactive oxygen species (ROS), decreased lipid peroxidation, and restored antioxidant capacity. Furthermore, FTA increased the expression of GPX4 and SLC7A11, indicating inhibition of ferroptosis. The ferroptosis inducer RSL3 partially reversed these protective effects, supporting the involvement of GPX4-associated ferroptosis regulation in the protective effects of FTA. In vivo, FTA alleviated mammary tissue injury, reduced inflammatory cell infiltration, and improved redox balance. These findings suggest that FTA may serve as a potential natural therapeutic agent for mastitis, providing a promising alternative to antibiotic-based treatments in dairy production.