Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 365, Issue -, Pages 19-29Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2018.12.019
Keywords
Myricetin; NLRP3 inflammasome; Ubiquitination; Reactive oxygen species
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Funding
- National Natural Science Foundation of China [81773016, 31471297]
- Zhejiang Provincial Natural Science Foundation of China [LY18C060001]
- Fundamental Research Funds for the Central Universities [419600*172210176]
- WeiJian Special Foundation
- Zhejiang UniversitySchool of Public Health
- Department of Science and Technology, Zhejiang Province [2016C33150]
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Myricetin is a plant-derived flavonoid that exhibits diverse pharmacological properties. The NLRP3 (NLR family, pyrin domain-containing 3 protein) inflammasome is a cytosolic multiprotein complex that plays a critical role in the innate immune response and pathogenesis of multiple inflammatory disorders. The present study found that myricetin inhibited NLRP3 inflammasome assembly via promotion of reactive oxygen species (ROS)-independent ubiquitination of NLRP3 and reduction of ROS-dependent ubiquitination of ASC (apoptosis-associated speck-like protein containing a CARD), which disrupted the interaction between ASC and NLRP3 and inhibited ASC oligomerization. This effect was further confirmed in vivo using mouse models of lipopolysaccharide (LPS)-induced sepsis and alum-induced peritonitis. These results suggest the therapeutic value of myricetin by targeting NLRP3-driven inflammatory diseases.
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