Background: Demethoxycurcumin (DMC), a natural derivative of curcumin, has anti-inflammatory
activities. However, the mechanism has not been fully elucidated.
Objective: The aim of the current study was to investigate the role of DMC on NLRP3 inflammasome
Methods: Protein expression was quantified by western blotting. Inflammatory cytokines were measured
by ELISA. Autophagosomes were evaluated by transmission electron microscopy.
Results: DMC inhibited LPS-stimulated NLRP3, pro-caspase-1, and pro-IL-1β expression. Meanwhile,
DMC diminished NLRP3-dependent IL-1β maturation, caspase-1 activation, IL-1β, and
IL-18 production caused by LPS plus ATP. Moreover, DMC induced autophagy and autophagy inhibitor
3-MA abrogated the role of DMC on NLRP3 inflammasome priming and subsequent activation.
DMC also inhibited LPS-stimulated phosphorylation and nuclear translocation of p65 NF-κB.
Additionally, DMC significantly increased the PPARγ expression, and the effects of DMC in NF-
κB inhibition, autophagy, and NLRP3 inflammasome priming were abrogated by specific PPARγ
Conclusion: The evidence presented here has confirmed that DMC increases PPARγ expression,
resulting in autophagy and NF-κB inhibition, and subsequently inhibits LPS-induced NLRP3 inflammasome
priming and subsequent activation.