Daidzein Relieves Lipopolysaccharide-Induced Mastitis Through Inhibiting MAPKs and AKT/NF-κB P65 Signaling Pathways

Mastitis in dairy cattle is a serious pathological process that causes significant economic losses to the farming industry. Daidzein is a dietary isoflavone, which exists in legumes and has been reported to have a wide range of biological activities. However, the relationship between daidzein and mastitis has not been reported. Therefore, the purpose of this study was to explore the effect of daidzein on mastitis and further probe into its potential mechanism based on the mice mastitis model induced by lipopolysaccharides. In vivo, the results showed that daidzein effectively alleviated the pathological damage of mammary tissue induced by lipopolysaccharides and significantly inhibited the increase of myeloperoxidase activity and inflammatory factors IL-6 and IL-1β. In vitro, the results showed that daidzein significantly inhibited the increase of pro-inflammatory cytokines IL-6 and IL-1β gene levels, as well as the increase of pro-inflammatory proteases inducible nitric oxide synthase and cyclooxygenase-2 protein levels. The molecular dynamics simulation showed that there was a strong hydrogen bond between daidzein and the amino acid residues of the serine/threonine protein kinase, c-Jun N-terminal kinase, extracellular signal–regulated kinase, and p38 mitogen–activated protein kinase. Further mechanism studies showed that daidzein significantly inhibited the activation of mitogen-activated protein kinase and threonine protein kinase/NF-κB P65 signaling pathways. Daidzein displayed a protective effect on lipopolysaccharide-induced mastitis in mice; the specific mechanism is associated to the release of interleukins (IL-6 and IL-1β) as well as the expression of reactive oxygen and nitrogen metabolite–metabolizing enzymes nitric oxide synthase and cyclooxygenase-2 through inhibiting MAPKs and threonine protein kinase /NF-κB signaling pathways.