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

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 K alpha 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 uM, respectively. Furthermore, compound 1 inhibited NLRP3 (NOD-, LRRand pyrin domain-containing protein 3) inflammasome-mediated interleukin-1 beta (IL-1 beta) production through activating autophagy.