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

  • J Agric Food Chem. 2025 Dec 10;73(49):31049-31064. doi: 10.1021/acs.jafc.5c04358.
Liping Wang  1 ,  Yuhao Chen  1 ,  Xiaoru Yang  1 ,  Yuze Ma  1 ,  Ruiyuan Yao  2 ,  Xiaoou Cheng  3 ,  Yanfeng Wang  1 ,  Huifang Hao  1 ,  Quan Fu  4 ,  Lili Bao  2  5 ,  Zhigang Wang  1
Affiliations
  • 1. State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China.
  • 2. School of Basic Medical Science, Inner Mongolia Medical University, Hohhot 010110, China.
  • 3. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 4. Department of Clinical Laboratory, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China.
  • 5. School of Nursing, Inner Mongolia Medical University, Hohhot 010110, China.
PMID: 41297906 DOI: 10.1021/acs.jafc.5c04358
Abstract

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.

Keywords
chlorogenic acid; ferroptosis; interleukin-6; lipopolysaccharide; milk products.
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