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.Key words erythraline; transforming growth factor-β activated kinase 1; anti-inflammation; toll-like receptorThe Erythrina genus (Leguminosae) includes more than 100 species and is distributed in South America and tropical and subtropical regions of South Asia. Erythrina crista-galli L. is commonly known as the cockspur coral tree. It is also called "Corticeira" in Brazil and its bark is used for the treatment of rheumatism, hepatitis, sedation, and hypnogenesis.

Saccharum Alhagi polysaccharide-1 and -2 promote the immunocompetence of RAW264.7 macrophages in�vitro

“…The cells were cultured at 37˚C in an atmosphere containing 5% CO 2 , and different concentrations (150, 300, and 600 mg/l) of SAP-1 and SAP-2 were added. The Griess method was performed to determine the levels of nitric oxide (NO) according to the protocol described in a previous study (14), and the absorbance was read at 540 nm using a microplate reader (Benchmark Plus; Bio-Rad Laboratories, Inc., Hercules, CA, USA).…”

Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus

“…TRAF6 is phosphorylated by IRAKs and binds to Ubc13 and Uev1A to form a complex that activates a mitogen-activating protein kinase kinase (MAPKKK) called transforming growth factor β-activating kinase-1 (TAK-1). Activated TAK-1 phosphorylates MKKs, which are upstream kinases of p38 MAPKs and JNK ( 85 ). p38 is involved in many cellular physiological and pathological processes, including apoptosis, cellular stress, the cell cycle, and the inflammatory response ( 86 ).…”

“…p38 is involved in many cellular physiological and pathological processes, including apoptosis, cellular stress, the cell cycle, and the inflammatory response ( 86 ). In addition, TAK-1 can activate the IκBα kinase (IKK) complex, consisting of the IKKα and IKKβ kinases and the hinge protein IKKγ ( 85 ). Phosphorylation of IκBα leads to its own degradation and the release of NF-κB ( Figure 2 ).…”

The genus Erythrina L.: A review on its alkaloids, preclinical, and clinical studies

“…Taking into account that toll‐like receptors (TLRs) are a key component of inflammatory process, Etoh et al () investigated the effects of erythraline ( 40 ), from E. crista‐galli barks, on TLR signaling molecules. The results suggested that the target molecule involved in erythraline ( 40 ) anti‐inflammatory activity is transforming growth factor‐β‐activated kinase (TAK‐1), a mitogen protein kinase activated by TLR ligants.…”