Alpha-Mangostin Attenuates Oxidative Stress and Apoptosis in Scopolamine-Induced Amnesic Rat Brains

Abstract

The extract from Garcinia mangostana L. pericarp was reported to scavenge radicals, inhibit acetylcholinesterase (AChE) activity, and improve spatial memory in scopolamine (SCOP)-induced amnesic rats. This study investigated α-mangostin (α-MG) neuroprotective effects against SCOP-induced neurotoxicity.The compound was evaluated for anti-AChE and antioxidant properties in vitro, and its preventive effect on apoptosis and oxidative stress in SCOP-treated rat brains. AChE inhibitory property of α-MG was assessed by fast blue B (FB) salt and β-naphthyl acetate (NA) and Ellman’s assays. The antioxidant properties of α-MG were assessed by ferric reducing antioxidant power (FRAP), scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2′-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid] (ABTS•+) radicals. Brain levels of malondialdehyde (MDA), lipid peroxidation marker, and activities of the caspase-3 enzyme, an apoptosis-related marker, were determined in SCOP-treated rats pretreated with donepezil (DPZ) and α-MG. IC50 of α-MG and DPZ for AChE activity were 64.23±0.22 and 32.46±0.14 mg/mL, respectively. α-MG and DPZ (100-600 µg/mL) gave FRAP values within the range of 20-410 µmol Fe2+/L. The IC50 of α-MG and DPZ for ABTS were 21.52±3.45 and 14.53±1.86 µg/mL, and for DPPH were 38.12±8.36 and 29.44±5.13 µg/mL, respectively. Prior given to SCOP-induced rats, DPZ and α-MG (50 and 100 mg/kg) reduced MDA levels, and pretreatment of DPZ and α-MG (50 mg/kg), but not α-MG (100 mg/kg), attenuated the increase of caspase-3 activity in cerebral cortex and hippocampus (P<0.05), but not in the basal forebrain. The present study is the first report of α-MG as a potential neuroprotective candidate, and its mechanism might be involved in ameliorating scopolamine-induced neurotoxicity via inhibition of lipid peroxidation and caspase-3 enzyme activity in the cerebral cortex and hippocampus.