Characterization and Biological Evaluation of Diterpenoids from Casearia graveolens

Biologically active substances that promote the neurite outgrowth of nerve cells against neuron degeneration may be useful for the treatment of Alzheimer's disease. In a continuing search for bioactive compounds from plants, an ethyl acetate-soluble extract of the twigs of Casearia graveolens showed moderate stimulatory activity of neurite outgrowth from PC12 cells. Further investigation to obtain bioactive compounds led to the isolation of 10 new clerodane diterpenoids, graveopenes A-J (1-10). Their structures including absolute configurations were elucidated based on analysis of their NMR spectroscopic data and experimental and calculated ECD spectra. Compounds 3-6 and 8 were shown to stimulate NGF-mediated neurite outgrowth from PC12 cells.