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JC2-11, a benzylideneacetophenone derivative, attenuates inflammasome activation
Scientific Reports ( IF 3.8 ) Pub Date : 2022-12-28 , 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 1
Affiliation  

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.



中文翻译:

JC2-11,一种亚苄基苯乙酮衍生物,可减弱炎性体激活

炎性体激活失调会导致慢性和过度炎症,从而导致多种疾病,例如代谢紊乱和癌症。因此,已经逐步进行了从天然材料中提取其调节剂的筛选。JC2-11 (JC) 旨在增强基于查耳酮的抗氧化活性,查耳酮在可食用植物中含量丰富,是类黄酮的前体。本研究检查了 JC 对人和小鼠巨噬细胞中炎性体激活的影响。JC 抑制白细胞介素 (IL)-1β 和乳酸脱氢酶的分泌,以及响应测试激活剂(即 NLRP3、NLRC4、AIM2 和非典型炎性体触发器)的 caspase-1 和 gasdermin D 的裂解。此外,JC 减弱了脂多糖 (LPS) 注射小鼠的 IL-1β 分泌,这是一种炎症小体介导的疾病模型。从机制上讲,JC 在炎性体的启动步骤中阻断了炎性体成分的表达,并中断了线粒体活性氧的产生。此外,JC 还能抑制 caspase-1 的活性。总之,JC 可能是一种候选的泛炎性小体抑制剂。

更新日期:2022-12-31
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