title: 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.
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China.
authors.forename: Dunjing
authors.initials: D
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Lv
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xu
authors.forename: Jizhen
authors.initials: J
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.forename: Chenghua
authors.initials: C
authors.lastname: Xiao
authors.forename: Deqin
authors.initials: D
authors.lastname: Geng
authors.forename: Yonghai
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D037621:Artemisinins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077332:Artesunate