Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1

doi:10.1016/j.phrs.2019.104348

CORC > 成都生物研究所 > 中国科学院成都生物研究所 > 国家天然药物工程技术研究中心 > 天然产物研究

	Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1
	Wu, Jiasi 2; Luo, Yu 2; Jiang, Qing 2; Li, Sheng 1; Huang, Wenge 2; Xiang, Li 2; Liu, Deming 2; Hu, Yingfan 2; Wang, Ping 2; Lu, Xiaoxia 1
刊名	PHARMACOLOGICAL RESEARCH
	2019
卷号	147 页码:104348
关键词	Coptisine Caspase-1 NLRP3 inflammasome NF-Kb Gout
ISSN号	1043-6618
DOI	10.1016/j.phrs.2019.104348
产权排序	2
文献子类	Article
英文摘要	Inflammasome mediates the activation of caspase-1, which promotes the secretion of proinflammatory cytokines. In this work, we aimed to investigate whether natural compounds from a Traditional Chinese Medicine prescription called San-Huang-Xie-Xin-Tang exert its clinical efficacy by inhibiting inflammasome activation and the underlying mechanism. The inhibitory effects of compounds on caspase-1 were evaluated in recombinant expressed caspase-1 protein and macrophages. Molecular docking was conducted to examine the interaction between compounds and caspase-1. The effects of the compounds on pro-inflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mechanism of the compounds on nucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome activation was investigated in macrophages. The anti-inflammasome effects of compounds were examined in mice stimulated by lipopolysaccharide (LPS) and monosodium urate crystal (MSU). Coptisine was the most potent inhibitor of caspase-1 in the San-Huang-Xie-Xin-Tang prescription. Coptisine adopted a favorable conformation at the active site of caspase-1. Coptisine significantly attenuated mature interleukin (IL)-1 beta secretion in RAW264.7 macrophages stimulated with LPS plus ATP, nigericin, or MSU, by blocking caspase-1 activation. Coptisine not only prevented NLRP3 inflammasome assembly by affecting the binding between pro-caspase-1 and apoptosis-associated speck-like protein containing a CARD, but also inhibited inflammasome priming by decreasing NLRP3 expression through inactivation of the nuclear factor-kappa B pathway. Moreover, coptisine prevented LPS-mediated IL-1 beta production and MSU-mediated mice paw edema by blocking NLRP3 inflammasome activation in vivo. Coptisine blocks NLRP3 inflammasome activation by inhibiting caspase-1 and may be useful for treating NLRP3 inflammasome-involved gouty arthritis.
学科主题	Pharmacology & Toxicology
URL标识	查看原文
WOS关键词	IL-1-BETA ; BERBERINE ; AUTOPHAGY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS记录号	WOS:000487565500012
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/31078]
专题	国家天然药物工程技术研究中心_天然产物研究
作者单位	1.Chinese Acad Sci, Chengdu Inst Biol, Key Lab Nat Med & Clin Translat, Chengdu 610041, Sichuan, Peoples R China 2.Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu 611137, Sichuan, Peoples R China;
推荐引用方式 GB/T 7714	Wu, Jiasi,Luo, Yu,Jiang, Qing,et al. Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1[J]. PHARMACOLOGICAL RESEARCH,2019,147:104348.
APA	Wu, Jiasi.,Luo, Yu.,Jiang, Qing.,Li, Sheng.,Huang, Wenge.,...&Meng, Xianli.(2019).Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1.PHARMACOLOGICAL RESEARCH,147,104348.
MLA	Wu, Jiasi,et al."Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1".PHARMACOLOGICAL RESEARCH 147(2019):104348.