Inhibition of Oxidative Neurotoxicity and Scopolamine-Induced Memory Impairment by γ-Mangostin: In Vitro and In Vivo Evidence

Abstract EN

Among a series of xanthones identified from mangosteen, the fruit of Garcinia mangostana L.

(Guttifereae), α- and γ-mangostins are known to be major constituents exhibiting diverse biological activities.

However, the effects of γ-mangostin on oxidative neurotoxicity and impaired memory are yet to be elucidated.

In the present study, the protective effect of γ-mangostin on oxidative stress-induced neuronal cell death and its underlying action mechanism(s) were investigated and compared to that of α-mangostin using primary cultured rat cortical cells.

In addition, the effect of orally administered γ-mangostin on scopolamine-induced memory impairment was evaluated in mice.

We found that γ-mangostin exhibited prominent protection against H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal death and inhibited reactive oxygen species (ROS) generation triggered by these oxidative insults.

In contrast, α-mangostin had no effects on the oxidative neuronal damage or associated ROS production.

We also found that γ-mangostin, not α-mangostin, significantly inhibited H2O2-induced DNA fragmentation and activation of caspases 3 and 9, demonstrating its antiapoptotic action.

In addition, only γ-mangostin was found to effectively inhibit lipid peroxidation and DPPH radical formation, while both mangostins inhibited β-secretase activity.

Furthermore, we observed that the oral administration of γ-mangostin at dosages of 10 and 30 mg/kg markedly improved scopolamine-induced memory impairment in mice.

Collectively, these results provide both in vitro and in vivo evidences for the neuroprotective and memory enhancing effects of γ-mangostin.

Multiple mechanisms underlying this neuroprotective action were suggested in this study.

Based on our findings, γ-mangostin could serve as a potentially preferable candidate over α-mangostin in combatting oxidative stress-associated neurodegenerative diseases including Alzheimer’s disease.