title: Xanthoceraside rescues learning and memory deficits through attenuating beta-amyloid deposition and tau hyperphosphorylation in APP mice.
abstract: Xanthoceraside, a triterpenoid saponin, has been shown to reverse cognitive deficits in several Alzheimer's disease (AD) animal models. However, the effects of xanthoceraside on the Aβ deposition pathology and the APP processing in AD are unclear. Here, we show that xanthoceraside at doses of 0.08 and 0.32 mg/kg/d for 6 months significantly improved learning and memory impairment in APP transgenic mice assessed by the Y maze and novel object recognition tests. Immunohistochemical analyses revealed that xanthoceraside strongly attenuated β-amyloid deposition in the brains of APP transgenic mice. Western blotting revealed that xanthoceraside decreased tau phosphorylation protein levels at Ser396 and Ser404 in the hippocampus; xanthoceraside also decreased APP protein levels and GSK-3β phosphorylation. These results suggest that xanthoceraside could be a promising novel candidate for the therapy of AD.
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Department of Pharmacology, Shenyang Medical Colleges, Shenyang 110034, PR China.
authors.forename: Ge
authors.initials: G
authors.lastname: Jin
authors.affiliation: Shenyang Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, PR China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xue-Fei
authors.initials: XF
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Tian-Yan
authors.initials: TY
authors.lastname: Chi
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiao
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: libozou@163.com.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Zou
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005106:Exploratory Behavior / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007859:Learning Disabilities / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008822:Mice, Transgenic; D010766:Phosphorylation; D021641:Recognition, Psychology / Q000187:drug effects; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D012503:Saponins; D014315:Triterpenes; D016875:tau Proteins; C548611:xanthoceraside; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3
keywords: Amyloid precursor protein; Aβ; Glycogen synthase kinase 3β; Hyperphosphorylated tau; Xanthoceraside