1. Academic Validation
  2. JC2-11, a benzylideneacetophenone derivative, attenuates inflammasome activation

JC2-11, a benzylideneacetophenone derivative, attenuates inflammasome activation

  • Sci Rep. 2022 Dec 28;12(1):22484. doi: 10.1038/s41598-022-27129-3.
Gilyoung Lee # 1 Huijeong Ahn # 1 Jang-Hyuk Yun 1 Jeongho Park 1 Eunsong Lee 1 Seikwan Oh 2 Geun-Shik Lee 3
Affiliations

Affiliations

  • 1 College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
  • 2 Department of Molecular Medicine, School of Medicine, Ewha Womans University, Gangseo-gu, Seoul, 07804, Republic of Korea.
  • 3 College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea. leegeun@kangwon.ac.kr.
  • # Contributed equally.
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.

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