Nardostachin from Nardostachys jatamansi exerts anti-neuroinflammatory effects through TLR4/MyD88-related suppression of the NF-κB and JNK MAPK signaling pathways in lipopolysaccharide-induced BV2 and primary microglial cells

Through searching for anti-neuroinflammatory metabolites from Nardostachys jatamansi extracts, nardostachin was revealed to exert anti-neuroinflammatory 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 cyclooxygenase-2 as well as pro-inflammatory cytokines, including interleukin (IL)-1 beta, IL-6, IL-12 and tumor necrosis factor-alpha in LPS-stimulated BV2 and rat primary microglial cells. In a mechanistic study, nardostachin exhibited inhibitory activity on the nuclear factor (NF)-kappa B signaling pathway in LPS-stimulated BV2 and rat primary microglial cells by repressing I kappa B-alpha phosphorylation and blocking NF-kappa B translocation. Furthermore, nardostachin exhibited inhibitory effects on LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK). Additionally, nardostachin repressed protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in LPS-induced BV2 and rat primary microglial cells. These results suggested that nardostachin exerts anti-neuroinflammatory effects on LPS-induced BV2 and rat primary microglial cells by suppressing the TLR4-MyD88-NF-kappa B and JNK MAPK pathways.