title: Amyrin attenuates scopolamine-induced cognitive impairment in mice.
abstract: Alzheimer's disease, a neurodegenerative disorder, is characterized by progressive cognitive impairment associated with the disruption of cholinergic neurotransmission. The aim of the present study was to evaluate the effect of α- or β-amyrin, a type of pentacyclic triterpene, on the cognitive impairment induced by scopolamine, a muscarinic acetylcholine receptor antagonist. To measure the abilities of various types of learning and memory, we conducted step-through passive avoidance task. Scopolamine induced deficits in learning and memory processes in mice, which were antagonized by a single administration of α-amyrin (2 or 4 mg/kg) or β-amyrin (4 mg/kg), respectively. Additionally, in vitro analysis revealed that acetylcholinesterase activity was inhibited by β-amyrin, but not by α-amyrin. Furthermore, Western blot analysis revealed that the expression levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK) and phosphorylated glycogen synthase kinase-3β (pGSK-3β) were significantly enhanced by a single administration of α- and β-amyrin in the hippocampus. Finally, the memory ameliorating effects of α- or β-amyrin on the scopolamine-induced cognitive impairments were significantly blocked by ERK inhibitor U0126. The present study suggests that α- and β-amyrin may ameliorate the cognitive impairment induced by hypocholinergic neurotransmission via the activation of ERK as well as GSK-3β signaling.
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Young Je
authors.initials: YJ
authors.lastname: Ahn
authors.forename: Sa Rang
authors.initials: SR
authors.lastname: Oh
authors.forename: Younghwan
authors.initials: Y
authors.lastname: Lee
authors.forename: Guyoung
authors.initials: G
authors.lastname: Kwon
authors.forename: Hyun
authors.initials: H
authors.lastname: Woo
authors.forename: Hyung Eun
authors.initials: HE
authors.lastname: Lee
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Jung
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D008813:Mice, Inbred ICR; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012601:Scopolamine / Q000494:pharmacology*
chemical_list: D018727:Muscarinic Antagonists; D009828:Oleanolic Acid; D012601:Scopolamine; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D000110:Acetylcholinesterase; C036380:beta-amyrin