Inhibition of Oxidative Neurotoxicity and Scopolamine-Induced Memory Impairment by -Mangostin: and Evidence.

Among a series of xanthones identified from mangosteen, the fruit of L. (Guttifereae), - and -mangostins are known to be major constituents exhibiting diverse biological activities. However, the effects of -mangostin on oxidative neurotoxicity and impaired memory are yet to be elucidated. In the present study, the protective effect of -mangostin on oxidative stress-induced neuronal cell death and its underlying action mechanism(s) were investigated and compared to that of -mangostin using primary cultured rat cortical cells. In addition, the effect of orally administered -mangostin on scopolamine-induced memory impairment was evaluated in mice. We found that -mangostin exhibited prominent protection against HO- or xanthine/xanthine oxidase-induced oxidative neuronal death and inhibited reactive oxygen species (ROS) generation triggered by these oxidative insults. In contrast, -mangostin had no effects on the oxidative neuronal damage or associated ROS production. We also found that -mangostin, not -mangostin, significantly inhibited HO-induced DNA fragmentation and activation of caspases 3 and 9, demonstrating its antiapoptotic action. In addition, only -mangostin was found to effectively inhibit lipid peroxidation and DPPH radical formation, while both mangostins inhibited -secretase activity. Furthermore, we observed that the oral administration of -mangostin at dosages of 10 and 30 mg/kg markedly improved scopolamine-induced memory impairment in mice. Collectively, these results provide both and evidences for the neuroprotective and memory enhancing effects of -mangostin. Multiple mechanisms underlying this neuroprotective action were suggested in this study. Based on our findings, -mangostin could serve as a potentially preferable candidate over -mangostin in combatting oxidative stress-associated neurodegenerative diseases including Alzheimer's disease.