Artesunate Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses by Suppressing TLR4, MyD88 Expression, and NF-κB Activation in Microglial Cells.

Abstract

Microglia are considered as a major target in the prevention of neuroinflammation by modulating the production of pro-inflammatory mediators. Artesunate, a water-soluble artemisinin derivative, exerts an anti-inflammatory effect. In the present study, we showed artesunate dose-dependently suppressed the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and interleukin-1beta (IL-1β) in BV2 microglial cells. In addition, artesunate inhibited LPS-induced expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and activation of nuclear factor kappa B (NF-κB) by blockade of inhibitor of NF-κB (IκB) degradation. This data indicate that artesunate attenuates the generation of proinflammatory mediators on LPS-stimulated BV-2 microglial cells. And this effect may be associated with the suppression of TLR4/MyD88/NF-κB signaling pathways. Therefore, artesunate may be a potential anti-neuroinflammatory agent.