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

Abstract

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.

• Authors: Youngmun Lee, Sunyoung Kim, Yeonsoo Oh, Young-Mi Kim, Young-Won Chin, Jungsook Cho
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2019 Pg. 3640753 ( 2019) ISSN: 1942-0994 [Electronic] United States
• PMID: 31019651 (Publication Type: Journal Article)

Chemical References

• Biphenyl Compounds
• Neurotoxins
• Picrates
• Xanthones
• Hydrogen Peroxide
• 1,1-diphenyl-2-picrylhydrazyl
• Scopolamine
• Amyloid Precursor Protein Secretases
• mangostin

Topics

• Amyloid Precursor Protein Secretases (metabolism)
• Animals
• Apoptosis (drug effects)
• Biphenyl Compounds (chemistry)
• Cell Survival (drug effects)
• Cells, Cultured
• Cerebral Cortex (pathology)
• Hydrogen Peroxide (toxicity)
• Lipid Peroxidation (drug effects)
• Memory Disorders (drug therapy)
• Mice, Inbred ICR
• Neurons (drug effects, metabolism, pathology)
• Neurotoxins (toxicity)
• Oxidative Stress (drug effects)
• Picrates (chemistry)
• Rats, Sprague-Dawley
• Scopolamine
• Xanthones (chemistry, pharmacology, therapeutic use)