PMID- 27343699 OWN - NLM STAT- MEDLINE DCOM- 20180105 LR - 20220317 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 111 DP - 2016 Sep TI - Stauntoside B inhibits macrophage activation by inhibiting NF-kappaB and ERK MAPK signalling. PG - 303-315 LID - S1043-6618(16)30098-6 [pii] LID - 10.1016/j.phrs.2016.06.022 [doi] AB - 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-kappaB (NF-kappaB) regulates the expression of an array of inflammatory mediators, cytokines and chemokine genes in activated macrophages. Therefore, NF-kappaB 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-kappaB 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-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) as well as the production of TNF-alpha 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 IKKalpha/beta activation, IkappaBalpha phosphorylation, p65 (ser536) NF-kappaB 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-kappaB activation associated inflammatory diseases. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Liu, Jianxin AU - Liu J AD - 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. FAU - Tang, Jinshan AU - Tang J AD - Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong Province 510632, PR China. Electronic address: gztangjinshan@126.com. FAU - Zuo, Yihan AU - Zuo Y AD - 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. FAU - Yu, Yang AU - Yu Y AD - Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong Province 510632, PR China. Electronic address: 1018yuyang@163.com. FAU - Luo, Pei AU - Luo P AD - 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. FAU - Yao, Xinsheng AU - Yao X AD - 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. FAU - Dong, Yan AU - Dong Y AD - Department of Immunology, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, PR China. Electronic address: 1462523594@qq.com. FAU - Wang, Peixun AU - Wang P AD - Department of Immunology, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, PR China. Electronic address: wpx@gzhtcm.edu.cn. FAU - Liu, Liang AU - Liu L AD - 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. FAU - Zhou, Hua AU - Zhou H AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160622 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Saponins) RN - 0 (Steroids) RN - 0 (stauntoside B) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Apoptosis/drug effects MH - Dose-Response Relationship, Drug MH - Enzyme Activation MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Inflammation/enzymology/genetics/*prevention & control MH - Inflammation Mediators/metabolism MH - Lipopolysaccharides/pharmacology MH - Macrophage Activation/*drug effects MH - Macrophages, Peritoneal/*drug effects/enzymology MH - Mice MH - NF-kappa B/*metabolism MH - Phosphorylation MH - RAW 264.7 Cells MH - RNA, Messenger/genetics/metabolism MH - Rats, Sprague-Dawley MH - Saponins/*pharmacology MH - Signal Transduction/*drug effects MH - Steroids/*pharmacology OTO - NOTNLM OT - Anti-inflammatory activity OT - Cynanchi stauntonii OT - Lipopolysaccharide OT - MAPK OT - NF-kappaB OT - Stauntoside B OT - Stauntoside B (PubChem CID: 101010462) EDAT- 2016/06/28 06:00 MHDA- 2018/01/06 06:00 CRDT- 2016/06/26 06:00 PHST- 2016/02/07 00:00 [received] PHST- 2016/06/21 00:00 [revised] PHST- 2016/06/21 00:00 [accepted] PHST- 2016/06/26 06:00 [entrez] PHST- 2016/06/28 06:00 [pubmed] PHST- 2018/01/06 06:00 [medline] AID - S1043-6618(16)30098-6 [pii] AID - 10.1016/j.phrs.2016.06.022 [doi] PST - ppublish SO - Pharmacol Res. 2016 Sep;111:303-315. doi: 10.1016/j.phrs.2016.06.022. Epub 2016 Jun 22.