Chlorogenic Acid Alleviates Ferroptosis Collectively Induced by Lipopolysaccharide and Interleukin-6 in Bovine Mammary Epithelial Cells

Lipopolysaccharide (LPS) from Gram-negative bacteria is a potent proinflammatory stimulates that drives the production of cytokines, including interleukin 6 (IL-6). Chlorogenic acid (CGA) is a plant-derived compound with potent anti-inflammatory activity. LPS, IL-6, and CGA are involved in programmed cell death and the release of inflammatory cytokines. However, the induction of ferroptosis by LPS and IL-6 in bovine mammary epithelial cells and the protective effects of CGA against this process are not fully understood. Here, LPS activated IL-6 production through a TLR4/CD36-dependent FAK/mTORC1 signaling axis in MAC-T cells. This pathway also mediated ferroptosis and the reduction in milk products induced by LPS and IL-6. CGA effectively mitigated these effects by suppressing ferroptosis. This study provides the novel mechanism whereby LPS orchestrates IL-6 release through the TLR4/CD36/FAK/mTORC1 axis, triggering ferroptosis and impairing milk synthesis in bovine mammary epithelial cells. It establishes CGA as a promising therapeutic agent against bovine mastitis.