title: Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats.
abstract: Ginsenoside Rg1, one of the major active ingredients isolated from Panax Ginseng, has been shown notable neuroprotective effects in memory impairment animals. However, the role of ginsenoside Rg1 on cognition capacity damaged by neurofibrillary tangles (NFTs) is still poorly understood, and the underlying mechanism remain to be fully elucidated. Okadaic acid (OKA), a potent phosphatase inhibitor, often apply to imitate Alzheimer's disease-like symptom damaged by neurofibrillary tangles, was used to investigate the effects of ginsenoside Rg1 on memory impairment and the related mechanisms in Sprague Dawley (SD) rats. The anti-dementic drug donepezil was used as a positive contrast. The results showed that OKA intracerebroventricular (i.c.v.) injection induced memory impairment, including changes in the ability of orientation navigate, spatial probe and relearning memory in behavioral test of Morris water maze (MWM). However, treatment with Rg1 and donepezil remarkably alleviated these changes. Also OKA treated rats showed memory impairment including increasing of phospho-tau, decreasing of phospho-GSK3β and the formation of β-amyloid in special brain regions, which were reversed by Rg1 (20 mg/kg) and donepezil (1 mg/kg) administration. All these indicating that ginsenoside Rg1 protects rats against OKA-induced neurotoxicity. The possible neuroprotective mechanism may be that Rg1 decreases OKA-induced memory impairment through GSK3β/tau signaling pathway and/or attenuating Aβ formation. Thus, these studies indicate that ginsenoside Rg1 might be a potential preventive drug for Alzheimer's disease.
authors.affiliation: State Key of Laboratory Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Xiu-Yun
authors.initials: XY
authors.lastname: Song
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hu
authors.forename: Shi-Feng
authors.initials: SF
authors.lastname: Chu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Xu
authors.forename: Yu-He
authors.initials: YH
authors.lastname: Yuan
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Niu
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease; D000818:Animals; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019319:Okadaic Acid; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D018696:Neuroprotective Agents; D016875:tau Proteins; D019319:Okadaic Acid; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C035054:ginsenoside Rg1