Anti-Inflammatory Lindenane Sesquiterpenoid Dimers from the Roots of Sarcandra glabra

Sarglaroids A-H (1-8), eight new lindenane dimers, and a monomer sarglaroid I (9), along with fourteen known analogues (10-23), were isolated from the roots of Sarcandra glabra. The planar structures and the absolute configurations were elucidated by HR-MS, NMR, ECD calculations, and X-ray diffraction crystallography. Sarglaroid A (1) was identified as a rare 8,9seco lindenane dimer with a unique 5/5/5 tricyclic system. The biological evaluation showed that compounds 1 and 13 potently inhibited NO production with IC50 values at 19.8 +/- 1.06 and 10.7 +/- 0.25 mu M, respectively, and had no cytotoxicity to RAW264.7 cells. Compound 6 significantly inhibited the LPS-/ATP-induced IL-1 ss release by inactivating the NLRP3 inflammasome through inhibiting the initiation and assembly by affecting the K+ efflux. Compounds 2 and 3 inhibited the proliferation of MCF-7 and MDAMB-231 with IC50 values ranging from 5.4 to 10.2 mu M.