Annatto Tocotrienol Attenuates NLRP3 Inflammasome Activation in Macrophages.

ABSTRACT: Accumulating evidence suggests that aberrant innate immunity is closely linked to metabolic diseases, including type 2 diabetes. In particular, activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and subsequent secretion of interleukin 1? (IL-1?) are critical determinants that precipitate disease progression. The seeds of annatto (Bixa orellana L.) contain tocotrienols (T3s), mostly (>90%) in the ? form (?T3). The aim of this study was to determine whether annatto T3 is effective in attenuating NLRP3 inflammasome activation in macrophages. Our results showed that annatto ?T3 significantly attenuated NLRP3 inflammasome by decreasing IL-1? reporter activity, IL-1? secretion, and caspase-1 cleavage against lipopolysaccharide (LPS) followed by nigericin stimulation. With regard to mechanism, annatto ?T3 1) reduced LPS-mediated priming of the inflammasome and 2) dampened reactive oxygen species production, the second signal required for assembly of the NLRP3 inflammasome in macrophages. Our work suggests that annatto ?T3 may hold therapeutic potential for delaying the onset of NLRP3 inflammasome-associated chronic metabolic diseases.

SUBMITTER: Buckner T 

PROVIDER: S-EPMC5998354 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature