title: Anti-amnesic effect of ESP-102 on Aβ(1-42)-induced memory impairment in mice.
abstract: The aim of this study was to characterize the effects of ESP-102 on the memory impairments and pathological changes induced by amyloid-β (Aβ)(1-42) peptide in mice. The ameliorating effect of ESP-102 on memory impairment was investigated using the passive avoidance and the Morris water maze tasks, and the pathological changes were identified by immunohistochemistry and western blotting. Aβ(1-42) peptide (3μg/3μl) was administered by intracerebroventricular injection. By the single administration of ESP-102 (100mg/kg, p.o), the memory impairment induced by Aβ(1-42) peptide was significantly attenuated (P<0.05). Moreover, ESP-102 (100mg/kg, p.o) significantly inhibited acetylcholinesterase (AChE) activity in the hippocampus compared to the Aβ(1-42) peptide-injected control group. In the subchronic treatment study, ESP-102 (50 or 100mg/kg/day, p.o) administration for seven days ameliorated the memory impairments induced by Aβ(1-42) peptide. Moreover, ESP-102 inhibited lipid peroxidation induced by Aβ(1-42) peptide in the hippocampus. Aβ(1-42)-induced increases in the expression of GFAP (an astrocyte marker) and inducible nitric oxide synthase (iNOS) in the hippocampal region were also attenuated by ESP-102 treatment. These results suggest that the ameliorating effect of ESP-102 on Aβ(1-42) peptide-induced memory impairment is mediated via its AChE inhibitory, antioxidative, and/or anti-inflammatory activities.
authors: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors: Dong Hyun
authors: DH
authors: Kim
authors: Won Young
authors: WY
authors: Jung
authors: Se Jin
authors: SJ
authors: Park
authors: Jong Min
authors: JM
authors: Kim
authors: Seungjoo
authors: S
authors: Lee
authors: Young Choong
authors: YC
authors: Kim
authors: Jong Hoon
authors: JH
authors: Ryu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000647:Amnesia / Q000139:chemically induced* / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; C546792:ESP 102; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D010936:Plant Extracts; C075222:amyloid beta-protein (1-42); D052247:Nitric Oxide Synthase Type II; D000110:Acetylcholinesterase