Nardostachin from Nardostachys jatamansi exerts anti­neuroinflammatory effects through TLR4/MyD88­related suppression of the NF­κB and JNK MAPK signaling pathways in lipopolysaccharide­induced BV2 and primary microglial cells.

ABSTRACT

Through searching for anti­neuroinflammatory metabolites from Nardostachys jatamansi extracts, nardostachin was revealed to exert anti­neuroinflammatory effects against lipopolysaccharide (LPS)­induced overproduction of nitric oxide and prostaglandin E2 in BV2 and rat primary microglial cells. Furthermore, nardostachin inhibited the production of inducible nitric oxide synthase and cyclooxygenase­2 as well as pro­inflammatory cytokines, including interleukin (IL)­1ß, IL­6, IL­12 and tumor necrosis factor­α in LPS­stimulated BV2 and rat primary microglial cells. In a mechanistic study, nardostachin exhibited inhibitory activity on the nuclear factor (NF)­κB signaling pathway in LPS­stimulated BV2 and rat primary microglial cells by repressing IκB­α phosphorylation and blocking NF­κB translocation. Furthermore, nardostachin exhibited inhibitory effects on LPS­induced phosphorylation of c­Jun N­terminal kinase (JNK) mitogen­activated protein kinase (MAPK). Additionally, nardostachin repressed protein expression of Toll­like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in LPS­induced BV2 and rat primary microglial cells. These results suggested that nardostachin exerts anti­neuroinflammatory effects on LPS­induced BV2 and rat primary microglial cells by suppressing the TLR4­MyD88­NF­κB and JNK MAPK pathways.