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| Prunetin Inhibits LPS-induced Inflammatory Response and Lipid Peroxidation in Bovine Mammary Epithelial Cells Through the Nrf2 Pathway |
| YAO Duan-Yang1, LAN Zheng-Hui1, WANG Ruo-Bing1, FENG Yan-Ni1, FU Kai-Qiang1, LI Hua-Tao1,*, Liu Xi-Wu2, CAO Lei3,* |
1 College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China;
2 Qingdao Animal Husbandry Workstation, Qingdao 266100, China;
3 Shandong Animal Husbandry and Veterinary Vocational College,Weifang 261061, China |
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Abstract Mastitis has a significant impact on the health and milk production of dairy cows (Bos taurus), resulting in reduced quality of dairy products and significant economic losses to the entire dairy industry. Prunetin (Pru) had biological activities such as anti allergic and anti-inflammatory properties. The aim of this study was to investigate the effects and mechanisms of prunetin on the inflammatory response and lipid peroxidation induced by lipopolysaccharide in bovine mammary epithelial cells (BMECs). The experiment was divided into control (CK) group, lipopolysaccharide (LPS) group, and lipopolysaccharide plus prunetin (LPS+Pru) groups at concentrations of 10, 20, 40, and 80 μmol/L, as well as a lipopolysaccharide plus ferrostatin-1 (Fer-1)(LPS+Fer-1) group. The expression levels of inflammatory cytokines, nuclear factor κB (NF-κB), and nuclear factor erythroid 2-related factor 2 / Kelch-like ECH-associated protein 1 (Nrf2/Keap1) proteins were detected in each group. The results showed that LPS significantly upregulated the gene and protein levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), IL-6, and IL-8. LPS also increased the content of Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA). Prunetin downregulated the genes of TNF-α, IL-1β, IL-6, IL-8, and their protein expression, upregulated the gene of Nrf2 and its protein expression, inhibited the NF-κB signaling pathway, and reduced cell death. Additionally, prunetin decreased the levels of Fe2+, ROS, and MDA while increasing the gene expression levels of glutathione peroxidase 4 (GPX4) and ferritin heavy polypeptide 1 (FTH1).These findings suggested that LPS induced inflammatory responses and lipid peroxidation in BMECs. Prunetin inhibited lipid peroxidation by activating Nrf2 and inhibiting NF-κB,and reducing the inflammatory response of BMECs induced by LPS, thereby exerting cytoprotective effects. This study provides theoretical support for the reduction of LPS induced inflammatory response and oxidative damage in BMECs by prunetin, and provides new ideas for protecting breast health in B. taurus.
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Received: 08 January 2024
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Corresponding Authors:
* huataoli@foxmail.com; caolei8004@163.com
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