Bioactive A-ring rearranged limonoids from the root barks of Walsura robusta

Screening active natural products, rapid identification, and accurate isolation are of great important for modern natural lead compounds discovery(1). We hereby reported the isolation of seven new neotecleanin-type limonoids (1—7), seven new limonoids with 5-oxatricyclo[5.4.0.11., 4.]hendecane ring system (8—14), and two new precursors (15—16) together with four known limonoids (17—20) from the root barks of Walsura robusta. Their structures, including their absolute configurations, were elucidated based on analyses of HR-ESI-MS, 1D/2D NMR, ECD spectrum calculations and single-crystal X-ray diffraction techniques. Compounds 2, 8, 9, 11, 13, 14, 18 showed significant anti-inflammatory activities in LPS-induced RAW 264.7 cell line, BV2 microglial cells, and Propionibacterium acnes-stimulated THP-1 human monocytic cells. Walrobsin M (11) exhibited anti-inflammatory activity with IC(50) value of 7.96±0.36 μmol/L, and down-regulated phosphorylation levels of ERK and p38 in a dose-dependent manner.