Memory-Enhancing Effects of Mangosteen Pericarp Water Extract through Antioxidative Neuroprotection and Anti-Apoptotic Action.

Mangosteen has long been utilized as a traditional medicine in Southeast Asia. Diverse extracts of mangosteen pericarp and its bioactive xanthones exhibit various bioactivities. However, the pharmacological potential of mangosteen pericarp water extract (MPW) has not been reported yet. This study used primary cultured rat cortical cells to investigate the effect of MPW on neurotoxicity. We found that MPW inhibited neurotoxicity and production of reactive oxygen species triggered by Aβ or excitatory amino acids. MPW inhibited caspase 3 activation and DNA fragmentation in Aβ- or N-methyl-D-aspartate-treated cells, suggesting an anti-apoptotic action. Additionally, MPW reduced lipid peroxidation and scavenged 1,1-diphenyl-2-picrylhydrazyl radicals, assuring its antioxidant property. Furthermore, MPW suppressed β-secretase and acetylcholinesterase activities. These findings prompted us to evaluate its effect on memory dysfunction in scopolamine-treated mice using Morris water maze test. Oral administration of MPW at the dosage of 50, 100, or 300 mg/kg for four days significantly decreased the latency time to find the platform and markedly increased the swimming time in the target quadrant. Taken together, our results suggest that MPW exerts memory-enhancing effect through antioxidative neuroprotection and anti-apoptotic action. Accordingly, MPW may have a potential to prevent or treat memory impairment associated with Alzheimer's disease.