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Octyl gallate has potent anti-inflammasome activity by directly binding to NLRP3 LRR domain

Title
Octyl gallate has potent anti-inflammasome activity by directly binding to NLRP3 LRR domain
Authors
ParkHanaKoRyeojinSeoJeonginAhnGuk YoungChoiSung-WookKwonMijungLeeSoo Young
Ewha Authors
이수영고려진권미정
SCOPUS Author ID
이수영scopusscopus; 고려진scopus; 권미정scopus
Issue Date
2024
Journal Title
Journal of Cellular Physiology
ISSN
0021-9541JCR Link
Citation
Journal of Cellular Physiology vol. 239, no. 4
Keywords
goutinflammasomeinflammationNLRP3octyl gallatesepsis
Publisher
John Wiley and Sons Inc
Indexed
SCIE; SCOPUS scopus
Document Type
Article
Abstract
The NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) inflammasome plays key roles in regulating inflammation. Numerous studies show that the abnormal activation of NLRP3 associates with the initiation and progression of various diseases. Hence, the NLRP3 inflammasome may be a promising therapeutic target for these diseases. Octyl gallate (OG) is a small molecule with antioxidant, antimicrobial, antifungal, and anti-inflammatory activities; however, the mechanism underlying its anti-inflammatory activity is still unclear. Here, we developed a screening system for NLRP3-inflammasome inhibitors. A total of 3287 small molecules were screened for inhibitors of nigericin-induced NLRP3 oligomerization. OG was identified as a novel inhibitor. We show that OG directly targets the LRR domain of NLRP3 and thereby blocks the inflammatory cascade of the NLRP3 inflammasome. This contrasts with the mode-of-action of other direct NLRP3 inhibitors, which all bind to the NACHT domain of NLRP3. Interestingly, OG also inhibits the priming step by downregulating the Raf-MEK1/2-ERK1/2 axis. Thus, OG inhibits the NLRP3 inflammasome by two distinct mechanisms. Importantly, OG injection ameliorated the inflammation in mouse models of foot gout and sepsis. Our study identifies OG as a potential therapeutic agent for NLRP3-associated diseases. © 2024 Wiley Periodicals LLC.
DOI
10.1002/jcp.31196
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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