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broussonin E suppresses LPS-induced inflammatory response in macrophages via inhibiting MAPK pathway and enhancing JAK2-STAT3 pathway

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Chinese Journal of Natural Medicines 2019年第5期17卷 372-380页

作者： HUANG Shao-Peng GUAN Xin KAI Guo-Yin XU Ya-Zhou XU Yuan WANG Hao-Jie PANG Tao ZHANG Lu-Yong LIU Ying School of Basic Medicine Center for Drug Screening and Pharmacodynamics Evaluation School of Pharmacy Guangdong Pharmaceutical University College of Pharmaceutical Science Zhejiang Chinese Medical University Jiangsu Key Laboratory of Drug Screening State Key Laboratory of Natural Medicines China Pharmaceutical University School of Medicine and Life Sciences Nanjing University of Chinese Medicine

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.

关键词： broussonin E Macrophage polarization Inflammation Janus kinase 2 Signal transducer and activator of transcription 3

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