title: Stauntoside B inhibits macrophage activation by inhibiting NF-κB and ERK MAPK signalling.
abstract: Inflammation 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.
authors.affiliation: 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.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong Province 510632, PR China. Electronic address: gztangjinshan@126.com.
authors.forename: Jinshan
authors.initials: J
authors.lastname: Tang
authors.affiliation: 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. Electronic address: zuoyihan521@qq.com.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong Province 510632, PR China. Electronic address: 1018yuyang@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 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. Electronic address: pluo@must.edu.mo.
authors.forename: Pei
authors.initials: P
authors.lastname: Luo
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong Province 510632, PR China. Electronic address: tyaoxs@jnu.edu.cn.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Immunology, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, PR China. Electronic address: 1462523594@qq.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Immunology, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, PR China. Electronic address: wpx@gzhtcm.edu.cn.
authors.forename: Peixun
authors.initials: P
authors.lastname: Wang
authors.affiliation: 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. Electronic address: lliu@must.edu.mo.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: 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. Electronic address: hzhou@must.edu.mo.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013256:Steroids / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D012503:Saponins; D013256:Steroids; C404167:stauntoside B; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Anti-inflammatory activity; Cynanchi stauntonii; Lipopolysaccharide; MAPK; NF-κB; Stauntoside B; Stauntoside B (PubChem CID: 101010462)