title: Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in intracerebroventricular-streptozotocin injected rats.
abstract: BACKGROUND
  Xanthoceraside, a novel triterpenoid saponin extracted from the fruit husks of Xanthoceras sorbifolia Bunge, reverses cognitive deficits in intracerebroventricular injection of Aβ25-35 or Aβ1-42 mice. However, whether xanthoceraside has a positive effect on hyperphosphorylated tau protein remains unclear.
  
  
  OBJECTIVE
  We investigated the effects of xanthoceraside on behavioural impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and its potential mechanisms.
  
  
  METHODS
  The rats were administered with xanthoceraside (0.06, 0.12 or 0.24 mg/kg) or vehicle once daily after STZ intracerebroventricular injections. The Y-maze test and novel object recognition test were performed 21 and 22 days after the second STZ injection, respectively. The levels of hyperphosphorylated tau, phosphatidylinositol-3-kinase (PI3K)/serine/threonine protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), protein phosphatase 1 (PP-1) and protein phosphatase 2A (PP-2A) were also tested by Western blot.
  
  
  RESULTS
  Xanthoceraside treatment significantly attenuated learning and memory impairments and reduced the level of STZ-induced hyperphosphorylated tau protein. Xanthoceraside also enhanced PP-2A and PP-1 expressions, increased PI3K (p85) and Akt (Ser473) phosphorylation and decreased GSK-3β (tyr216) phosphorylation.
  
  
  CONCLUSIONS
  Xanthoceraside has protective effect against learning and memory impairments and inhibits tau hyperphosphorylation in the hippocampus, possibly through the inhibition of the PI3K/Akt-dependent GSK-3β signalling pathway and an enhancement of phosphatases activity.
authors: Peng
authors: P
authors: Liu
authors: Li-Bo
authors: LB
authors: Zou
authors: Li-Hua
authors: LH
authors: Wang
authors: Qing
authors: Q
authors: Jiao
authors: Tian-Yan
authors: TY
authors: Chi
authors: Xue-Fei
authors: XF
authors: Ji
authors: Ge
authors: G
authors: Jin
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1 / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use*; D013311:Streptozocin / Q000008:administration & dosage; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D018697:Nootropic Agents; D012503:Saponins; D014315:Triterpenes; D016875:tau Proteins; C548611:xanthoceraside; D013311:Streptozocin; D058539:Phosphatidylinositol 3-Kinase; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2
references: Neuroscience. 2012 Mar 29;206:190-200
references: 22233781
references: Exp Neurol. 2010 Jun;223(2):304-10
references: 19744482
references: J Biol Chem. 1995 Jan 13;270(2):823-9
references: 7822317
references: Neurotoxicology. 2009 Nov;30(6):1000-7
references: 19666049
references: Am J Pathol. 2009 Nov;175(5):2089-98
references: 19815707
references: Neuropharmacology. 2010 Nov;59(6):542-50
references: 20708632
references: Neurotoxicology. 2012 Jun;33(3):370-83
references: 22387731
references: Pharmacol Rep. 2010 Mar-Apr;62(2):265-72
references: 20508281
references: Neuroscience. 2011 Mar 17;177:298-307
references: 21238544
references: J Neurosci. 2007 Dec 12;27(50):13635-48
references: 18077675
references: J Biol Chem. 1984 Apr 25;259(8):5301-5
references: 6425287
references: Neuropharmacology. 2011 Feb-Mar;60(2-3):460-6
references: 21044639
references: J Clin Exp Neuropsychol. 2012;34(9):989-98
references: 22913619
references: Toxicology. 2008 Jan 14;243(1-2):43-50
references: 17980476
references: Neuroreport. 2004 Apr 29;15(6):955-9
references: 15076714
references: Behav Neurosci. 1998 Oct;112(5):1199-208
references: 9829797
references: J Neural Transm (Vienna). 2006 Jan;113(1):93-102
references: 15959856
references: Behav Brain Res. 2010 Feb 11;207(1):144-50
references: 19822174
references: Neurochem Int. 2011 Mar;58(4):458-71
references: 21215781
references: JAMA. 2002 Nov 6;288(17):2123-9
references: 12413371
references: EMBO J. 2001 Jan 15;20(1-2):27-39
references: 11226152
references: Neuropharmacology. 2012 Feb;62(2):871-81
references: 21958557
references: Neuropharmacology. 2010 Sep-Oct;59(4-5):276-89
references: 20149808
references: PLoS One. 2010 Nov 29;5(11):e15497
references: 21124738
references: J Neurochem. 2009 Mar;108(5):1116-25
references: 19077054
references: Neurochem Int. 2011 Aug;59(2):235-50
references: 21672577
references: Trends Mol Med. 2009 Mar;15(3):112-9
references: 19246243
references: Expert Rev Proteomics. 2008 Apr;5(2):207-24
references: 18466052
references: Science. 2002 May 31;296(5573):1655-7
references: 12040186
references: Psychopharmacology (Berl). 2012 Jan;219(1):181-90
references: 21735075
references: J Neuropathol Exp Neurol. 1999 Sep;58(9):1010-9
references: 10499443
references: FEBS Lett. 2006 May 22;580(12):2922-7
references: 16529745
references: Curr Alzheimer Res. 2012 Dec;9(10):1182-90
references: 22515493
references: Neuroscience. 2011 Jan 26;173:30-6
references: 21093547
references: Biochemistry. 2006 Mar 14;45(10):3125-33
references: 16519507
references: Brain Res. 1998 Jun 29;797(2):267-77
references: 9666145
references: J Cell Sci. 2004 Nov 15;117(Pt 24):5721-9
references: 15537830
references: J Clin Neurosci. 2010 Aug;17(8):1025-33
references: 20537899
references: Acta Neuropathol. 2009 Jul;118(1):53-69
references: 19184068
references: EMBO J. 2004 Jul 7;23(13):2586-96
references: 15192701
references: Pharmacol Biochem Behav. 2011 Mar;98(1):140-9
references: 21167197
references: Eur Neuropsychopharmacol. 2011 Mar;21(3):261-73
references: 21195590
references: Neurobiol Aging. 2012 Feb;33(2):430.e5-18
references: 21256630
references: FEBS Lett. 1996 Apr 8;384(1):25-30
references: 8797796
references: J Neurochem. 1995 Aug;65(2):732-8
references: 7616230
references: J Biol Chem. 1997 Oct 3;272(40):25326-32
references: 9312151
references: Neurobiol Aging. 2012 Feb;33(2):433.e11-20
references: 21429623
references: Brain Res Brain Res Rev. 2000 Aug;33(1):95-130
references: 10967355
references: J Neurochem. 1993 Sep;61(3):921-7
references: 8395566
references: J Ethnopharmacol. 2011 Feb 16;133(3):1109-16
references: 21129477
references: J Neurochem. 2001 Apr;77(1):94-102
references: 11279265
references: FEBS Lett. 1997 Jul 14;411(2-3):183-8
references: 9271202
references: Neuroreport. 2003 Feb 10;14(2):257-60
references: 12598741
references: Neuropsychobiology. 2010;61(4):188-96
references: 20299813
references: Life Sci. 2001 Jan 19;68(9):1021-9
references: 11212865
references: Neurobiol Dis. 2009 Sep;35(3):359-67
references: 19523516
references: J Neurosci. 2000 Apr 1;20(7):2567-74
references: 10729337
references: Neuroscience. 2011 Jan 26;173:169-78
references: 21055450
references: J Neurochem. 2006 Feb;96(4):1005-15
references: 16412093
references: Cell Signal. 2012 Jan;24(1):265-71
references: 21946431
references: J Asian Nat Prod Res. 2009 Dec;11(12):1019-27
references: 20183271
references: Neurochem Int. 2007 Jan;50(2):435-42
references: 17116346
references: Neurochem Int. 2010 Jul;56(8):955-61
references: 20398714
references: Neurobiol Learn Mem. 2011 Mar;95(3):296-304
references: 21167950
references: Neurobiol Aging. 2009 Jan;30(1):81-92
references: 17590240
references: Neuropharmacology. 2009 Mar;56(4):779-87
references: 19705549
references: Neuroscience. 2013 May 15;238:97-113
references: 23415789
references: Eur J Neurosci. 2005 Oct;22(8):1942-50
references: 16262633
references: Brain Res. 2009 Nov 3;1296:148-63
references: 19698704
references: J Neurosci Res. 2001 Sep 1;65(5):425-31
references: 11536326
references: Int J Neuropsychopharmacol. 2004 Dec;7(4):387-90
references: 15315719
references: Neurobiol Aging. 2012 Dec;33(12):2798-806
references: 22382406