Chrysanthemum zawadskii (C. zawadskii) is used in
traditional East Asian medicine for the treatment of various diseases, including inflammatory disease. However, it has remained unclear whether extracts of C. zawadskii inhibit
inflammasome activation in macrophages. The present study assessed the inhibitory effect of an
ethanol extract of C. zawadskii (CZE) on the activation of the
inflammasome in macrophages and the underlying mechanism. Bone marrow-derived macrophages were obtained from wild-type C57BL/6 mice. The release of IL-1β and
lactate dehydrogenase in response to
nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3)
inflammasome activators, such as
ATP,
nigericin and
monosodium urate (MSU) crystals, was significantly decreased by CZE in
lipopolysaccharide (LPS)-primed BMDMs. Western blotting revealed that CZE inhibited
ATP-induced caspase-1 cleavage and IL-1β maturation. To investigate whether CZE inhibits the priming step of the NLRP3
inflammasome, we confirmed the role of CZE at the gene level using RT-qPCR. CZE also downregulated the gene expression of NLRP3 and pro-IL-1β as well as NF-κB activation in BMDMs in response to LPS. Apoptosis-associated speck-like
protein containing a caspase-recruitment domain (CARD) oligomerization and speck formation by NLRP3
inflammasome activators were suppressed by CZE. By contrast, CZE did not affect NLR family CARD domain-containing
protein 4 or absent in
melanoma 2
inflammasome activation in response to Salmonella typhimurium and
poly(dA:dT) in LPS-primed BMDMs, respectively. The results revealed that three key components of CZE, namely
linarin,
3,5-dicaffeoylquinic acid and
chlorogenic acid, decreased IL-1β secretion in response to
ATP,
nigericin and MSU. These findings suggest that CZE effectively inhibited activation of the NLRP3
inflammasome.