Protective mechanism of milk-derived bioactive peptides VPP and IPP against lipopolysaccharide-induced inflammation in bovine mammary epithelial cells and a mouse mastitis model

• DOI: 10.1017/anr.2025.1
• Publication Date: 2025-04-11T11:51:26Z
• Authors: Meifei Zhu; Ruike Wei; Jingyan Li; Jiayi Bao; Lin Wei; Xinyu Yu; Zheng Zhou; Fuliang Hu; Shanshan Li

Abstract Bovine mastitis harms milk quality and cattle health. Val-Pro-Pro (VPP) Ile-Pro-Pro (IPP) are well-known milk-derived bioactive peptides with anti-inflammatory activity. However, the impact of VPP IPP on remain unknown. This study aimed to investigate effects underlying mechanisms in lipopolysaccharide (LPS)-induced inflammation. When cells were treated LPS (1 µg/mL) for 24 h, protein levels pro-inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin(IL)-1β IL-6)) chemokine (monocyte chemotactic protein-1 (MCP-1)) markedly increased, level cytokine (IL-10) was reduced. Both concentrations 50 100 µM reversed these phenomena further inhibited expression β-casein induced by LPS. In a mouse model, different (300, 600 µM/kg) pretreatment alleviated histopathological lesions mammary gland suppressed mRNA TNFα, IL1β, IL6 also maintained integrity blood–milk barrier mice. RNA-seq analyses indicated that enriched phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) mitogen-activated (MAPK) signaling pathways likely contribute changes observed ( P < 0.05 |log 2 fold change (FC)| ≥ 1). Notably, fibronectin identified as an important hub protein–protein interaction (PPI) analysis molecular docking combined dynamics simulation. summary, exerted protective effect LPS-induced inflammation regulating PI3K/AKT pathway via fibronectin.