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

Publication date: Available online 20 July 2019Source: Pharmacological ResearchAuthor(s): Jiasi Wu, Yu Luo, Qing Jiang, Sheng Li, Wenge Huang, Li Xiang, Deming Liu, Yingfan Hu, Ping Wang, Xiaoxia Lu, Guolin Zhang, Fei Wang, Xianli MengAbstractInflammasome 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)-1β secretion in RAW264.7 macrophages stimulat...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research