Discovery of Limonoids from as Potential Leads against Neuroinflammation.

Discovery of new natural products with both anti-inflammatory effects on activated microglia and protective activity on dopaminergic neurons is a new strategy to find new drug leads against neuroinflammation in Parkinson's disease. In this work, nine new limonoids, named thaigranatumins A-I (-), and two new protolimonoids, named thaigranatumins J () and K (), were obtained from seeds of the Thai mangrove, . The structures of these compounds were established by analysis of spectroscopic data, single-crystal X-ray diffraction (Cu Kα), and comparison of experimental and calculated ECD spectra. Thaigranatumin A (), containing a C-16/C-30 δ-lactone ring-D and a -substituted C-O-C-bridged tetrahydrofuran ring-F, is the first limonoid featuring a unique 6/6/6/6/6/5/5-fused heptacyclic framework. Thaigranatumin G () exhibited both inhibitory effects on the protein expression of iNOS, COX2, and IL-1β in lipopolysaccharide-stimulated mouse microglia BV2 cells and neuroprotective activity against rotenone-induced injury in mouse midbrain dopaminergic neuron MN9D cells in a dose-dependent manner. Preliminary bioassays indicated that thaigranatumin G might be a valuable lead against neuroinflammation, thus warranting further studies.