• Jianxin Liu, Jinshan Tang, Yihan Zuo, Yang Yu, Pei Luo, Xinsheng Yao, Yan Dong, Peixun Wang, Liang Liu, and Hua Zhou.
• Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wailong, Taipa, Macau, PR China; State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Avenida Wailong, Taipa, Macau, PR China; College of Pharmacy, Hunan University of Medicine, Huaihua, Hunan Province 418000, PR China. Electronic address: liujx3385@gmail.com.
• Pharmacol. Res. 2016 Sep 1; 111: 303-315.

AbstractInflammation is a defensive reaction of body to resist foreign invasion. However, it has been demonstrated that excessive and continuous inflammatory responses contribute to various inflammatory diseases, including rheumatoid arthritis. Nuclear factor-κB (NF-κB) regulates the expression of an array of inflammatory mediators, cytokines and chemokine genes in activated macrophages. Therefore, NF-κB has become an attractive drug target for controlling inflammation. In this study, stauntoside B, a C21 steroidal glycosides compound isolated from a Chinese medicine Cynanchi Stauntonii, was for the first time found to suppress macrophage activation induced by lipopolysaccharide (LPS) in RAW264.7 cells and rat primary peritoneal macrophages and could be a potent NF-κB inhibitor. The results showed that stauntoside B significantly reduced the release of inflammatory mediators in activated RAW264.7 cells and rat peritoneal macrophages, including nitric oxide (NO) and prostaglandin E2 (PGE2). The mRNA expressions of pro-inflammatory mediators and cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), microsomal prostaglandin synthetase-1 (mPGES-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) as well as the production of TNF-α and IL-6 were also inhibited by stauntoside B. Mechanistic investigation implies that the anti-inflammatory activity of stauntoside B could result from the suppression of LPS-induced IKKα/β activation, IκBα phosphorylation, p65 (ser536) NF-κB phosphorylation, and ERK MAPK activation by stauntoside B treatment in activated macrophages. Meanwhile, stauntoside B could induce apoptosis in LPS-activated macrophages. The current study suggests stauntoside B being a valuable candidate drug for the treatment of inflammatory diseases, especially for NF-κB activation associated inflammatory diseases.Copyright © 2016 Elsevier Ltd. All rights reserved.

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