Broussonin E suppresses LPS-induced inflammatory response in macrophages via inhibiting MAPK pathway

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Macrophages play an important role in inflammation,and excessive and chronic activation of macrophages leads to systemic inflammatory diseases,such as atherosclerosis and rheumatoid arthritis.In this paper,we explored the anti-inflammatory effect of broussonin E,a novel phenolic compound isolated from the barks of Broussonetia kanzinoki,and its underlying molecular mechanisms.We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells,involving TNF-α,IL-1β,IL-6,COX-2 and iNOS.And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10,CD206 and arginase-1 (Arg-1) in LPS-stimulated RAW264.7 cells.Further,we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK.Moreover,we found that broussonin E could activate janus kinase (JAK) 2,signal transducer and activator of transcription (STAT) 3.Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway,WP1066.Taken together,our results showed that broussonin E could suppress inflammation by modulating macrophages activation state via inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway,and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.
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