Curcuma phaeocaulis Inhibits NLRP3 Inflammasome in Macrophages and Ameliorates Nanoparticle-Induced Airway Inflammation in Mice

Abstract

The activation of NLRP3 results in the assembly of inflammasome that regulates caspase-1 activation and the subsequent secretion of bioactive interleukin (IL)-1β. Excessive activation of the NLRP3 inflammasome is mechanistically linked to diverse pathophysiological conditions, including airway inflammation. Here, we discovered that <i>Curcuma phaeocaulis</i> can suppress caspase-1 activation and processing of pro-IL-1β into mature cytokine in macrophages stimulated with NLRP3 inflammasome activators, such as SiO₂ or TiO₂ nanoparticles. Furthermore, in the bronchoalveolar lavage fluids of animals administered the nanoparticles, the in vitro effects of <i>C. phaeocaulis</i> translated into a decrease in IL-1β levels and cell infiltration. Demethoxycurcumin (DMC) and curcumin were found to be responsible for the inflammasome inhibitory activity of <i>C. phaeocaulis</i>. Interestingly, in contrast to the previously reported higher antioxidant- and NFκB-inhibitory activities of curcumin, DMC exhibited approximately two-fold stronger potency than curcumin against nanoparticle induced activation of NLRP3 inflammasome. In the light of these results, both compounds seem to act independently of their antioxidant- and NFκB-inhibitory properties. Although how <i>C. phaeocaulis</i> inhibits nanoparticle-activated NLRP3 inflammasome remains to be elucidated, our results provide a basis for further research on <i>C. phaeocaulis</i> extract as an anti-inflammatory agent for the treatment of disorders associated with excessive activation of NLRP3 inflammasome.