Six New Polyoxygenated Xanthones from Garcinia cowa and Their Neuroprotective Effects on Glutamate-Mediated Hippocampal Neuronal HT22 Cell Death

Abstract

Six new polyoxygenated xanthones, garcicowanones F？H (1-3), norcowanol A？B (4-5), andgarcinone F (6) along with twelve known compounds 7？18 were obtained from the latex of Garcinia cowa Roxb.ex Choisy. All new compounds have a 1,3,7-trioxygenatedor 1,3,6,7-tetra oxygenate dxanthonenucleus and differ from majority of xanthones from G. cowa by hydratedsidechains. Compounds1,7,8 and 18 exhibited significant neuroprotective effects on glutamate-mediated hippocampal neuronal HT22 cell death. In particular,compound1 exhibited the most potent neuroprotective effect with >80% cell viability in the concentration range of 2.9？115μM. Further studies on compound1 showed that it decreased cellular Ca2+ influx and inhibits cellular reactive oxygen species generation in HT22 cells. A Western blot analysis showed that MAPK phosphorylation, Bax, and AIF translocation dramatically increased upon treatment with 5 mM glutamate and decreased upon a co-treatment with compound1