ReferenceID 3545
Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1
Pharmacol Res
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 prescripti
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Record Fields
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- Reference Id
- 3545
- Evidence Id
- 20135
- Core Evidence Id
- 20135
- Source Reference Id
- 399
- Herb2 Reference Id
- HBREF000708
- Subject Paper Key
- HBIN021430_31336157
- Pubmed Id
- 31336157
- Doi
- 10.1016/j.phrs.2019.104348
- Paper Title
- Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1
- Paper Abstract
- 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)-1β 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-κB pathway. Moreover, coptisine prevented LPS-mediated IL-1β 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.
- Journal
- Pharmacol Res
- Publish Year
- 2019
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Gouty Arthritis
- Paper Title Cn
- Paper Title En
- Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1
- Bilingual Status
- semi_complete