title: Inhibitory effect of erythraline on Toll-like receptor signaling pathway in RAW264.7 cells.
abstract: Erythraline, isolated from the bark of Erythrina crista-galli which are used as Brazilian medicine plant for the treatment of inflammation diseases, suppressed nitric oxide (NO) production and induction of inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Because of Toll-like receptor (TLR) 4 and its signal transduction are indispensable to the production of NO and iNOS expression by LPS, we investigated the effects of erythraline on TLR signaling molecules. Western blot analysis revealed that the degradation of inhibitor of nuclear factor (NF)-κB (IκB) by LPS was suppressed by erythraline. Moreover, erythraline inhibited not only LPS-induced phosphorylation of IκB kinase (Ikk) but also phosphorylation of mitogen-activated protein kinases (MAPKs). However, it showed no effect on LPS -induced phosphorylation of transforming growth factor (TGF)-β-activated kinase (TAK) 1 that exists upstream of Ikk and MAPKs, and is required for the activation of these signaling molecules on TLR signaling pathway. These results suggested that erythraline might have inhibited the kinase activity of TAK1. Furthermore, these results were supported from the inhibitory pattern of erythraline on TLR signaling molecules when the cells were stimulated by TLR2 ligand, peptidoglycan which activates the same pathway as LPS on TLR signal transduction.
authors.affiliation: Faculty of Pharmacy, Iwaki Meisei University, 5–5–1 Iino, Chuo-dai, Iwaki, Fukushima 970–8551, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Etoh
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Kim
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ohsaki
authors.forename: Kanki
authors.initials: K
authors.lastname: Komiyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004895:Erythrina; D026121:Indole Alkaloids / Q000494:pharmacology*; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010457:Peptidoglycan; D024301:Plant Bark; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000893:Anti-Inflammatory Agents; D026121:Indole Alkaloids; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010457:Peptidoglycan; D051193:Toll-Like Receptors; D000099151:MAP Kinase Kinase Kinase 7; C496317:Nos2 protein, mouse; C586471:erythraline