Brazilin is a Natural Product Inhibitor of the NLRP3 Inflammasome

Emily Mcmahon, Sherihan El Sayed, Jack Green, Christopher Hoyle, Lorna Fitzpatrick, Emma Jones, Eve Corrie, Rebecca Kelly, Mairi Challinor, Sally Freeman, Richard Bryce, Catherine B. Lawrence, David Brough, Paul Kasher

Research output: Contribution to journalArticle

Abstract

Excessive or aberrant NLRP3 inflammasome activation has been implicated in the progression and initiation of many inflammatory conditions; however, currently no NLRP3 inflammasome inhibitors have been approved for therapeutic use in the clinic. Here we have identified that the natural product brazilin effectively inhibits both priming and activation of the NLRP3 inflammasome in cultured murine macrophages, a human iPSC microglial cell line and in a mouse model of acute peritoneal inflammation. Through computational modelling, we predict that brazilin can adopt a favourable binding pose within a site of the NLRP3 protein which is essential for its conformational activation. Our results not only encourage further evaluation of brazilin as a therapeutic agent for NLRP3-related inflammatory diseases, but also introduce this small-molecule as a promising scaffold structure for the development of derivative NLRP3 inhibitor
compounds.
Original languageEnglish
Article number108968
JournaliScience
Volume27
Issue number2
Early online date19 Jan 2024
DOIs
Publication statusPublished - 1 Feb 2024

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