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Sesquiterpene lactone dimers from Artemisia lavandulifolia inhibit interleukin-1β production in macrophages through activating autophagy
Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2020-11-04 , DOI: 10.1016/j.bioorg.2020.104451
Qiaoqiao Wang , Tian Zhang , Chang-Qiang Ke , Chunping Tang , Sheng Yao , Ligen Lin , Yang Ye

Twelve new sesquiterpene lactone dimers, lavandiolides A–L (1–12), were isolated from the whole plants of Artemisia lavandulifolia. Among them, compounds 1–6 are 1,3-linked Diels-Alder adducts between two guaianolide monomers, and 7–12 are 2,4-linked sesquiterpene lactone dimers. Their structures were elucidated by comprehensive analysis of HRESIMS, 1D and 2D NMR spectra. Their absolute configurations were determined by ECD spectra and single-crystal X-ray diffraction analyses with Cu Kα radiation. The nitric oxide (NO) inhibitory effect of all the isolates was assessed on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compounds 1, 3, 7 and 9 showed potent inhibitory effects on NO production, with IC50 values of 0.61 ± 0.15, 1.64 ± 0.04, 1.89 ± 0.16, and 1.40 ± 0.23 μM, respectively. Furthermore, compound 1 inhibited NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome-mediated interleukin-1β (IL-1β) production through activating autophagy.



中文翻译:

淡紫色蒿的倍半萜烯内酯二聚体通过激活自噬抑制巨噬细胞中白介素1β的产生

青蒿的整个植物中分离出十二种新的倍半萜烯内酯二聚体,Lavandiolides A–L(1–12其中,化合物1-6是两个愈创木酚内酯单体之间的1,3-连接的Diels-Alder加合物,而7-12是2,4-连接的倍半萜烯内酯二聚体。通过对HRESIMS,1D和2D NMR光谱进行全面分析,阐明了它们的结构。它们的绝对构型由ECD光谱和CuKα辐射的单晶X射线衍射分析确定。评估所有分离株对一氧化氮(NO)抑制作用对脂多糖(LPS)刺激的RAW264.7巨噬细胞的影响。化合物137图9显示了对NO生成的有效抑制作用,IC 50值分别为0.61±0.15、1.64±0.04、1.89±0.16和1.40±0.23μM。此外,化合物1通过激活自噬抑制了炎症小体介导的白介素1β(IL-1β)产生的NLRP3(含NOD,LRR和含吡啶结构域蛋白3)。

更新日期:2020-11-15
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