Evodiamine Relieve LPS-Induced Mastitis by Inhibiting AKT/NF-κB p65 and MAPK Signaling Pathways

Abstract

Evodiamine, an alkaloid component in the fruit of Evodia, has been shown to have biological functions such as antioxidant and anti-inflammatory. But whether evodiamine plays an improvement role on mastitis has not been studied. To investigate the effect and mechanism of evodiamine on lipopolysaccharide (LPS)-induced mastitis was the purpose of this study. In animal experiments, the mouse mastitis model was established by injecting LPS into the canals of the mammary gland. The results showed that evodiamine could significantly relieve the pathological injury of breast tissue and the production of pro-inflammatory cytokines and inhibit the activation of inflammation-related pathways such as AKT, NF-κB p65, ERK1/2, p38, and JNK. In cell experiments, the mouse mammary epithelial cells (mMECs) were incubated with evodiamine for 1 h and then stimulated with LPS. Next, pro-inflammatory mediators and inflammation-related signal pathways were detected. As expected, our results showed that evodiamine notably ameliorated the inflammatory reaction and inhibit the activation of related signaling pathways of mMECs. All the results suggested that evodiamine inhibited inflammation by inhibiting the phosphorylation of AKT, NF-κBp65, ERK1/2, p38, and JNK thus the LPS-induced mastitis was ameliorated. These findings suggest that evodiamine maybe a potential drug for mastitis because of its anti-inflammatory effects.

Keywords: NF-κB; evodiamine; mastitis; mitogen-activated protein kinase (MAPK)..