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Src and Syk contribute to the anti-inflammatory activities of Achyranthes aspera ethanolic extract

Lee, Jeong-Oog, Yang, Woo Seok, Park, Jae Gwang, Jeong, Deok, Kim, Han Gyung, Yoon, Kee Dong, Aravinthan, Adithan, Kim, Jong-Hoon, Kim, Eunji, Cho, Jae Youl
Journal of ethnopharmacology 2017 v.206 pp. 1-7
Achyranthes aspera, IKappaB kinase, anti-inflammatory activity, cytotoxicity, ethanol, gastritis, gene expression, gene expression regulation, genes, immunoblotting, inducible nitric oxide synthase, inflammation, luciferase, messenger RNA, nitric oxide, phosphorylation, reverse transcriptase polymerase chain reaction, traditional medicine, transcription factor NF-kappa B, tumor necrosis factor-alpha
Nuclear factor-kappa B (NF-κB) plays pivotal roles in inflammation. Src and Syk are two tyrosine kinases that act upstream of NF-κB signaling. Although Achyranthes aspera L. (A. aspera) has been used as a traditional medicine to treat fevers and inflammatory ailments and heal wounds, the molecular mechanisms of its anti-inflammatory actions are not yet fully understood.In this study, we evaluated the anti-inflammatory effect of A. aspera ethanol extract (Aa-EE). To determine the mechanism by which Aa-EE dampens the inflammatory response, nitric oxide (NO) production and the mRNA expression levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) were examined by Griess assay and RT-PCR. Luciferase assays and immunoblotting were also conducted to examine how Aa-EE regulates the NF-κB pathway.Aa-EE reduced NO production up to 60% without any cytotoxicity. This extract was found to downregulate the mRNA expression levels of inflammatory genes. Aa-EE blocked NF-κB promoter activity induced by both TNF-α and adaptor molecule MyD88 (about 70% and 40%, respectively). Moreover, nuclear translocation of p65 and IκBα phosphorylation were also inhibited. Furthermore, Aa-EE inactivated two upstream signaling molecules, the Src and Syk kinases. In accordance with these data, the kinase activities of Src and Syk were decreased by 50% and 80%, respectively. The anti-inflammatory action of Aa-EE was also confirmed in a gastritis model.Our data suggest that Aa-EE targets NF-κB to exert its anti-inflammatory properties by suppressing Src and Syk. Therefore, our study raises the possibility that this extract can be developed as a novel natural anti-inflammatory remedy.