A Synthetic Small Molecule F240B Decreases NLRP3 Inflammasome Activation by Autophagy Induction.

ABSTRACT: Conjugated polyenes are a class of widely occurring natural products with various biological functions. We previously identified 4-hydroxy auxarconjugatin B (4-HAB) as anti-inflammatory agent with an IC₅₀ of ~20 µM. In this study, we synthesized a new anti-inflammatory 4-HAB analogue, F240B, which has an IC₅₀ of less than 1 µM. F240B dose-dependently induced autophagy by increasing autophagic flux, LC3 speck formation and acidic vesicular organelle formation. F240B inhibited NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome activation through autophagy induction. In a mechanistic study, F240B inhibited interleukin (IL)-1β (IL-1β) precursor expression, promoted degradation of NLRP3 and IL-1β, and reduced mitochondrial membrane integrity loss in an aut

SUBMITTER: Wu CH 

PROVIDER: S-EPMC7793731 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature