Ethanol extract of Chrysanthemum zawadskii inhibits the NLRP3 inflammasome by suppressing ASC oligomerization in macrophages

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Title
Ethanol extract of Chrysanthemum zawadskii inhibits the NLRP3 inflammasome by suppressing ASC oligomerization in macrophages
Author(s)
A R Jang; H N Lee; Jung Joo Hong; Y M Kim; J H Park
Bibliographic Citation
Experimental and Therapeutic Medicine, vol. 25, no. 3, pp. 128-128
Publication Year
2023
Abstract
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.
Keyword
Chrysanthemum zawadskiiNucleotide?binding oligomerization domain?like receptor family pyrin domain containing 3 inflammasomeIL?1βApoptosis?associated speck?like Protein containing a caspase?recruitment domain oligomerizationBone marrow?derived macrophage
ISSN
1792-0981
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/etm.2023.11827
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > National Primate Research Center > 1. Journal Articles
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