Sesquiterpene lactone dimers from Artemisia lavandulifolia inhibit interleukin-1β production in macrophages through activating autophagy

Abstract

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.