alpha-mangostin attenuates oxidative stress and apoptosis in scopolamine-induced amnesic rat brains

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.