Meroterpenoids and sesquiterpene dimers from Sarcandra glabra with anti-neuroinflammatory activity

Sarcandra glabra (Thunb.) Nakai is abundantly artificially cultivated for industrial use as an essential pharmaceutical and chemical raw material in China. In this work, five new meroterpenoids ( 1 – 5 ), along with one analog ( 6 ) and six known sesquiterpene dimers ( 7 – 12 ) were isolated from Sarcandra glabra . The chemical structures, including absolute configurations, were deduced by extensive spectroscopic methods combined with quantum mechanical electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations, Mo 2 (OAc) 4 -induced ECD experiments, and customizable DP4 + probability analysis. Compounds 1 – 6 are biogenetically assembled by the cyclization of gentisicacid and monoterpene, featuring a novel 6/6/6 -fused ring system. Compounds 4 and 5 possess significant inhibitory effects on nitric oxide (NO) production against lipopolysaccharide (LPS)-induced microglia (BV2) cells, while compounds 8 and 9 displayed an approximately equal effect to Dexamethasone . The analysis of the protein-protein interaction (PPI) network and molecular docking showed 4 and 5 could play an anti-neuroinflammatory role by regulating heat shock proteins 90AA1 (Hsp90AA1). This study provided evidence for further research and utilization of S . glabra in anti-neuroinflammatory medicinal products. • Five new meroterpenoids, along with one analog and six known sesquiterpene dimers were isolated from Sarcandra glabra . • Their structures were established by comprehensive spectroscopic analyses. • Compounds 4 and 5 possess significant anti-neuroinflammatory effects. • Compounds 4 and 5 could play an anti-neuroinflammatory role by regulating Hsp90AA1.