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来自Physalis minima的13,14-sec withaphysalins及其对NLRP3炎症酶激活的抑制作用

Bintao Hu¹, Xia Peng², Chunping Tang¹

¹State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Bioorganic chemistry

|July 26, 2024

概括

来自Physalis minima的新化合物,包括罕见的类固醇,可以抑制NLRP3炎症酶. 这些seco-withaphysalins通过阻断巨细胞中的caspase-1激活和IL-1β产生,有效地降低了炎症反应.

科学领域:

自然产品化学化学
免疫学免疫学免疫学
药理学药理学是指药理学的学科.

背景情况:

植物植物是生物活性天然产品的来源.
在炎症性疾病中,NLRP3炎症体起着至关重要的作用.
开发NLRP3炎症酶激活的新型抑制剂是关键的治疗目标.

研究的目的:

为了从Physalis minima中分离和表征新的二氧化素.
通过向NLRP3炎症酶来评估这些化合物的抗炎潜力.
阐明最强大的抑制剂的作用机制.

主要方法:

使用光谱数据,电子圆形二极化和X射线晶体学,分离和阐明seco-withaphysalins的结构.
在Raw264.7细胞中NLRP3炎症酶抑制的评估.
对酶-1激活,IL-1β产生,NF-κB激活和NLRP3/IL-1β表达的分析.

主要成果:

他们分离了七种新的13,14-seco-withaphysalins,包括两种新的骨架.
化合物1-3,5,6和8显著降低了NLRP3依赖的caspase-1激活.
化合物1和2通过降低NLRP3炎症酶激活的调节,显示出强大的,剂量依赖的IL-1β产生抑制.

结论:

菲萨利斯最小产生结构独特的seco-withaphysalins,具有强大的抗炎性质.
化合物1和2是有前途的NLRP3炎症酶抑制剂,在原始化步骤的下游起作用.
这些发现表明,seco-withaphysalins在炎症条件下具有潜在的治疗应用.

关键词:

13,14-seco与physalin在一起的时间.抗炎药物抗炎药物抗炎药物在NLRP3中,NLRP3是NLRP3中的一个.身体的最小值 (Physalis minima) 是一个基本的数值.

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