Aucubin suppresses lipopolysaccharide-induced pro-inflammatory responses by blocking the NF-κB translocation signaling pathways in activated microglial cells

Abstract

Aucubin is an iridoid glycoside with demonstrable hepatoprotective and anti-osteoporotic effects. Herein, using microglial cells and lipopolysaccharide (LPS) to induce inflammatory responses, we studied the signaling pathways involved in the anti-inflammatory action of aucubin and their influence on the expression of several genes known to be involved in inflammation. Aucubin inhibited LPS-stimulated pro-inflammatory responses by suppressing the production of nitric oxide and prostaglandin E 2 . Furthermore, aucubin inhibited inducible nitric oxide synthase and cyclooxygenase-2 at both the protein and mRNA levels. In addition, aucubin inhibited pro-inflammatory cytokine production in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that aucubin inhibited the LPS-induced activation of nuclear factor-kappa B (NF-κB) translocation and phosphorylation of phosphatidylinositol 3-kinases (PI3K)/Akt as well as of mitogen-activated protein kinases (MAPKs), which are upstream molecules responsible for controlling inflammatory reactions. These results suggest that aucubin may exert anti-neuroinflammatory responses by suppressing the LPS-induced expression of pro-inflammatory mediators by blocking the activation of NF-κB, PI3K/Akt, and MAPK signaling pathways in microglial cells. • Aucubin inhibited LPS-induced pro-inflammatory mediators in microglial cells. • Aucubin suppressed LPS-induced phosphorylation of MAPKs and PI3K/Akt. • Aucubin blocked activation of NF-κB translocation and the DNA-binding activity of NF-κB. • Aucubin may exert anti-neuroinflammatory responses for neurodegenerative diseases.