Abstract

The effects of licocoumarone (LC) isolated from Glycyrrhiza uralensis were studied in LPS-stimulated RAW 264.7 macrophages. Our study demonstrated that LC dose-dependently attenuated LPS-induced NO production by down-regulating iNOS expression. Additionally, the treatment with LC inhibited LPS-induced expression of cytokines including IL-1β, IL-6 and IL-10, but not TNF-α, at both mRNA and protein levels. Similar suppressive effects of LC were observed on LPS-stimulated murine peritoneal macrophages as well. Furthermore, LC significantly reduced LPS-stimulated NF-κB activation by inhibition of IκBα degradation and p65 phosphorylation. The results from NF-κB-luc reporter gene assay further support the inhibitory effect of LC on NF-κB activation. Further studies showed that LC also interfered with the MAPKs and STAT3 signaling pathways, which are typical inflammatory signaling pathways triggered by LPS . Taken together, these results show that LC attenuates LPS-induced cytokine gene expression in RAW 264.7 macrophages through mechanisms that involve NF-κB, MAPKs and STAT3 signaling pathways, but the pattern of inhibition differs from that of a global immunosuppresant. Our study indicates that LC is a functional constituent of Glycyrrhiza uralensis with potential implications in infectious and immune-related diseases.