JC2-11, a benzylideneacetophenone derivative, attenuates inflammasome activation

Gilyoung Lee, Huijeong Ahn, Jang Hyuk Yun, Jeongho Park, Eunsong Lee, Seikwan Oh, Geun Shik Lee

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Dysregulation of inflammasome activation induces chronic and excess inflammation resulting in several disorders, such as metabolic disorders and cancers. Thus, screening for its regulator derived from natural materials has been conducted progressively. JC2-11 (JC) was designed to enhance the antioxidant activity based on a chalcone, which is abundant in edible plants and a precursor of flavonoids. This study examined the effects of JC on inflammasome activation in human and murine macrophages. JC inhibited the secretion of interleukin (IL)-1β and lactate dehydrogenases, and the cleavage of caspase-1 and gasdermin D in response to the tested activators (i.e., NLRP3, NLRC4, AIM2, and non-canonical inflammasome triggers). In addition, JC attenuated IL-1β secretion from lipopolysaccharide (LPS)-injected mice, an inflammasome-mediating disease model. Mechanistically, JC blocked the expression of the inflammasome components during the priming step of the inflammasome, and interrupted the production of mitochondrial reactive oxygen species. In addition, JC inhibited the activity of caspase-1. In conclusion, JC may be a candidate pan-inflammasome inhibitor.

Original languageEnglish
Article number22484
JournalScientific Reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
We would like to acknowledge all authors for their highly valuable contributions to this special issue. Also, we would like to express our gratitude to the reviewers whose constructive comments helped to improve the quality of the articles. The authors would like to thank “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil” (CAPES, Finance Code 001) and “Conselho Nacional de Desenvolvimento Científico e Tecnológico–Brasil” (CNPq) for grants and fellowships.

Funding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (NRF-2018R1A2B2004097 and NRF-2018R1D1A1B07048337).

Publisher Copyright:
© 2022, The Author(s).

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