| Moderate inflammation is a host defense response against infection,tissue damage,and other pathological stimulation,but excessive inflammation or chronic inflammation will lead to pathological conditions and plays a vital role in human diseases.After being recruited to the site of inflammation,macrophages are induced into distinct functional phenotypes under different immune microenvironment,mainly undergoing the classically activated M1 phenotype and the alternatively M2 phenotype.Dysregulation of the M1-M2 balance is often associated with inflammatory diseases;therefore,studying mechanisms of macrophage polarization may reveal new drug targets for inflammatory diseases.Gentiana rigescens and Phyllanthus emblica Linn are Yunnan’s abundant medicinal plants,and this study was performed to assess their anti-inflammatory effects and to investigate the underlying mechanisms,which may provide data for the exploitation of their use in clinical applications in controlling inflammatory diseases.We investigated their ability to inhibit LPS-induced expression of cytokines and inflammatory signaling pathway activation in THP-1-derived macrophages.We observed Gentiana rigescens and gentiopicroside significantly inhibited pro-inflammatory cytokines TNF-α,IL-6,and IL-1β expression at the m RNA level compared with the control.Moreover,gentiopicroside suppressed IκBα degradation and p65,TBK1 phosphorylation.At the same time,the Phyllanthus emblica Linn significantly suppressed LPS-stimulated TNF-α,MCP-1,IL-6,IL-1β,and COX2 m RNA expression.It significantly reduced IκBα and TBK1 degradation and phosphorylation levels,which subsequently led to the suppression of p65 nuclear translocation.These results suggested that Gentiana rigescens and Phyllanthus emblica Linn have potent anti-inflammatory effects,and the molecular mechanism involves inhibiting the NF-κB and the STING-TBK1 pathway activation cascade. |
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