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Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in intracerebroventricular-streptozotocin injected rats

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Abstract

Rationale

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.

Objectives

We investigated the effects of xanthoceraside on behavioural impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and its potential mechanisms.

Materials and 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.

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References

  • Agrawal R, Tyagi E, Shukla R, Nath C (2009) A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia. Neuropharmacology 56:779–787

    Article  CAS  PubMed  Google Scholar 

  • Agrawal R, Tyagi E, Shukla R, Nath C (2011) Insulin receptor signaling in rat hippocampus: a study in STZ (ICV) induced memory deficit model. Eur Neuropsychopharmacol 21:261–273

    Article  CAS  PubMed  Google Scholar 

  • Annika R, Nenad B, Inga V, Bengt W, Rivka R, Richard CF (2004) Akt activity in Alzheimer's disease and other neurodegenerative disorders. Neuroreport 15:955–959

    Article  Google Scholar 

  • Avila J (2006) Tau phosphorylation and aggregation in Alzheimer's disease pathology. FEBS Lett 580:2922–2927

    Article  CAS  PubMed  Google Scholar 

  • Baki L, Shioi J, Wen P, Shao ZP, Schwarzman A, Gama-Sosa M, Neve R, Robakis NK (2004) PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. EMBO J 23:2586–2596

    Article  CAS  PubMed  Google Scholar 

  • Bitner RS, Markosyan S, Nikkel AL, Brioni JD (2011) In-vivo histamine H3 receptor antagonism activates cellular signaling suggestive of symptomatic and disease modifying efficacy in Alzheimer's disease. Neuropharmacology 60:460–466

    Article  CAS  PubMed  Google Scholar 

  • Brunden KR, Ballatore C, Crowe A, Smith AB, Lee VMY, Trojanowski JQ (2010) Tau-directed drug discovery for Alzheimer's disease and related tauopathies: a focus on tau assembly inhibitors. Exp Neurol 223:304–310

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Rev 33:95–130

    Article  CAS  PubMed  Google Scholar 

  • Bulic B, Pickhardt M, Mandelkow EM, Mandelkow E (2010) Tau protein and tau aggregation inhibitors. Neuropharmacology 59:276–289

    Article  CAS  PubMed  Google Scholar 

  • Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655–1657

    Article  CAS  PubMed  Google Scholar 

  • Che Y, Piao CS, Han PL, Lee JK (2001) Delayed induction of alpha B-crystallin in activated glia cells of hippocampus in kainic acid-treated mouse brain. J Neurosci Res 65:425–431

    Article  CAS  PubMed  Google Scholar 

  • Chi TY, Wang LH, Qu C, Yang BZ, Ji XF, Wang Y, Okuyama T, Yoshihito O, Zou LB (2009) Protective effects of xanthoceraside on learning and memory impairment induced by Abeta (25–35) in mice. J Asian Nat Prod Res 11:1019–1027

    Article  CAS  PubMed  Google Scholar 

  • Chi TY, Wang LH, Ji XF, Li W, Wang Y, Zou LB (2010) Protective effects of xanthoceraside on learning and memory impairment induced by intracerebroventricular injections of Aβ1–42 in mice. J Shenyang Pharm Univ 27:314–319

    CAS  Google Scholar 

  • Corcoran NM, Martin D, Hutter-Paier B, Windisch M, Nguyen T (2010) Sodium selenate specifically activates PP2A phosphatase, dephosphorylates tau and reverses memory deficits in an Alzheimer's disease model. J Clin Neurosci 17:1025–1033

    Article  CAS  PubMed  Google Scholar 

  • Crespo-Biel N, Canudas AM, Camins A, Palla’s M (2007) Kainate induces AKT, ERK and cdk5/GSK3β pathway deregulation, phosphorylates tau protein in mouse hippocampus. Neurochem Int 50:435–442

    Article  CAS  PubMed  Google Scholar 

  • Cross DA, Culbert AA, Chalmers KA, Facci L, Skaper SD, Reith AD (2001) Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. J Neurochem 77:94–102

    Article  CAS  PubMed  Google Scholar 

  • Damgaard T, Larsen DB, Hansen SL, Grayson B, Neill JC, Plath N (2010) Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats. Behav Brain Res 207:144–150

    Article  CAS  PubMed  Google Scholar 

  • Deng YQ, Li B, Liu Y, Iqbal K, Grundke-Iqbal I, Gong CX (2009) Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain. Am J Pathol 175:2089–2098

    Article  CAS  PubMed  Google Scholar 

  • Fujimura M, Usuki F, Sawada M, Takashima A (2009) Methylmercury induces neuropathological changes with tau hyperphosphorylation mainly through the activation of the c-jun-N-terminal kinase pathway in the cerebral cortex, but not in the hippocampus of the mouse brain. NeuroToxicology 30:1000–1007

    Article  CAS  PubMed  Google Scholar 

  • Gao SM, Ma K, Du XH, Li FL (2002) Advances in research on Xanthoceras sorbifolia. Chin Bull Botany 19:296–301

    Google Scholar 

  • Gong CX, Singh TJ, Grundke-Iqbal I, Iqbal K (1993) Phosphoprotein phosphatase activities in Alzheimer disease brain. J Neurochem 61:921–927

    Article  CAS  PubMed  Google Scholar 

  • Gong CX, Shaikh S, Wang JZ, Zaidi T, Grundke-Iqbal I, Iqbal K (1995) Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain. J Neurochem 65:732–738

    Article  CAS  PubMed  Google Scholar 

  • Gould TD, Einat H, Bhat R, Manji HK (2004) AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol 7:1–4

    Article  Google Scholar 

  • Guadagna S, Esiri MM, Williams RJ, Francis PT (2012) Tau phosphorylation in human brain: relationship to behavioral disturbance in dementia. Neurobiol Aging 33:2798–2806

    Article  CAS  PubMed  Google Scholar 

  • Haege S, Galetzka D, Zechner U, Haaf T, Gamerdinger M, Behl C, Hiemke C, Schmitt U (2010) Spatial learning and expression patterns of PP1 mRNA in mouse hippocampus. Neuropsychobiology 61:188–96

    Article  CAS  PubMed  Google Scholar 

  • Hanger DP, Anderton BH, Noble W (2009) Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 15:112–119

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa M, Jakes R, Crowther RA, Lee VM, Ihara Y, Goedert M (1996) Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein. FEBS Lett 384:25–30

    Article  CAS  PubMed  Google Scholar 

  • Hetman M, Cavanaugh JE, Kimelman D, Xia Z (2000) Role of glycogen synthase kinase-3beta in neuronal apoptosis induced by trophic withdrawal. J Neurosci 20:2567–2574

    CAS  PubMed  Google Scholar 

  • Hong M, Chen DCR, Klein PS, Lee VMY (1997) Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. J Biol Chem 272:25326–25332

    Article  CAS  PubMed  Google Scholar 

  • Iqbal K, Liu F, Gong CX, Alonso Adel C, Grundke-Iqbal I (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 118:53–69

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Irvine K, Laws KR, Gale TM, Kondel TK (2012) Greater cognitive deterioration in women than men with Alzheimer's disease: a meta analysis. J Clin Exp Neuropsychol 34:989–998

    Article  PubMed  Google Scholar 

  • Jeugd AV, Ahmed T, Burnouf S, Belarbi K, Hamdame M, Grosjean ME, Humez S, Balschun D, Blum D, Buée L, Hooge RD (2011) Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission. Neurobiol Learn Mem 95:296–304

    Article  PubMed  Google Scholar 

  • Johnson GV, Stoothoff WH (2004) Tau phosphorylation in neuronal cell function and dysfunction. J Cell Sci 117:5721–5729

    Article  CAS  PubMed  Google Scholar 

  • Kamata PK, Rai S, Swarnkar S, Shukla R, Ali S, Najmi AK, Nath C (2013) Okadaic acid-induced Tau phosphorylation in rat brain: Role of NMDA receptor. Neuroscience 238:97–113

    Article  Google Scholar 

  • Katelin F, Hansen, Sakamoto K, Gary A, Wayman, Impey S, Obrietan K (2010) Transgenic miR132 alters neuronal spine density and impairs novel object recognition memory. PloS ONE 5:1–7

    Google Scholar 

  • Koshibu K, Gräff J, Mansuy IM (2011) Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation. Neuroscience 173:30–6

    Article  CAS  PubMed  Google Scholar 

  • Lannert H, Hoyer S (1998) Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav Neurosci 112:1199–1208

    Article  CAS  PubMed  Google Scholar 

  • Lee CW, Lau KF, Miller CC, Shaw PC (2003) Glycogen synthase kinase-3 beta-mediated tau phosphorylation in cultured cell lines. Neuroreport 14:257–260

    Article  CAS  PubMed  Google Scholar 

  • Lee KY, Koh SH, Noh MY, Kim SH, Lee YJ (2008) Phosphatidylinositol-3-kinase activation blocks amyloid beta-induced neurotoxicity. Toxicology 243:43–50

    Article  CAS  PubMed  Google Scholar 

  • Li T, Paudel HK (2006) Glycogen synthase kinase 3beta phosphorylates Alzheimer's disease specific Ser396 of microtubule-associated protein tau by a sequential mechanism. Biochemistry 45:3125–33

    Article  CAS  PubMed  Google Scholar 

  • Li X, Lu F, Tian Q, Yang Y, Wang Q, Wang JZ (2006) Activation of glycogen synthase kinase-3 induces Alzheimer-like tau hyperphosphorylation in rat hippocampus slices in culture. J Neural Transm 113:93–102

    Article  CAS  PubMed  Google Scholar 

  • Lin CL, Chen TF, Chiu MJ, Way TD, Lin JK (2009) Epigallocatechin gallate (EGCG) suppresses β-amyloid-induced neurotoxicity through inhibiting c-Abl/FE65 nuclear translocation and GSK3β activation. Neurobiol Aging 30:81–92

    Article  CAS  PubMed  Google Scholar 

  • Lindwall G, Cole R (1984) Phosphorylation affects the ability of tau protein to promote microtubule assembly. J Biol Chem 259:5301–5305

    CAS  PubMed  Google Scholar 

  • Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2005) Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. Eur J Neurosci 22:1942–1950

    Article  PubMed  Google Scholar 

  • Liu XX, Ji XF, Lu LL, Yang BZ, Wang LH, Zou LB (2007) Improvement of ethanol extract from husk of Xanthoceras sorbifolia on rats with learning and memory dysfunction. Chin Tradit Herb Drugs 12:106–110

    Google Scholar 

  • Lu P, Mamiya T, Lu LL, Mouri A, Ikejima T, Kim HC, Zou LB, Nabeshima T (2012) Xanthoceraside attenuates amyloid β peptide25–35-induced learning and memory impairments in mice. Psychopharmacology 1:181–190

    Article  Google Scholar 

  • Lucas JJ, Hernandez F, Gomez-Ramos P, Moran MA, Hen R, Avila J (2001) Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J 20:27–39

    Article  CAS  PubMed  Google Scholar 

  • Maesako M, Uemura K, Kubota M, Hiyoshi K, Ando K, Kuzuya A, Kihara T, Asada M, Akiyama HAND, Kinoshita A (2011) Effect of glycogen synthase kinase 3β-mediated presenilin 1 phosphorylation on amyloid β production is negatively regulated by insulin receptor cleavage. Neuroscience 177:298–307

    Article  CAS  PubMed  Google Scholar 

  • Martin L, Latypova X, Terro F (2011a) Post-translational modifications of tau protein: implications for Alzheimer's disease. Neurochem Int 58:458–471

    Article  CAS  PubMed  Google Scholar 

  • Martin L, Page G, Terro F (2011b) Tau phosphorylation and neuronal apoptosis induced by the blockade of PP2A preferentially involve GSK3β. Neurochem Int 59:235–250

    Article  CAS  PubMed  Google Scholar 

  • Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Titani K, Ihara Y (1995) Proline-directed and non-proline-directed phosphorylation of PHF-tau. J Biol Chem 270:823–829

    Article  CAS  PubMed  Google Scholar 

  • Munoz-Montano JR, Moreno FJ, Avila J, Diaz-Nido J (1997) Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons. FEBS Lett 411:183–188

    Article  CAS  PubMed  Google Scholar 

  • Nanfaro F, Cabrera R, Bazzocchini V, Laconi M, Yunes R (2010) Pregnenolone sulfate infused in lateral septum of male rats impairs novel object recognition memory. Pharmacol Reports 62:265–272

    CAS  Google Scholar 

  • Noh MY, Koh SH, Kim Y, Kim HY, Cho GW, Kim SH (2009) Neuroprotective effects of donepezil through inhibition of GSK-3 activity in amyloid-β-induced neuronal cell death. J Neurochem 108:1116–1125

    Article  CAS  PubMed  Google Scholar 

  • Ordóñez C, Navarro A, Pérez C, Martínez E, del Valle E, Tolivia J (2012) Gender differences in apolipoprotein D expression during aging and in Alzheimer disease. Neurobiol Aging 33:433.e11–433.e20

    Article  Google Scholar 

  • Pei JJ, Grundke-Iqbal I, Iqbal K, Bogdanovic N, Winblad B, Cowburn RF (1998) Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer's disease neurofibrillary degeneration. Brain Res 797:267–277

    Article  CAS  PubMed  Google Scholar 

  • Pei JJ, Braak E, Braak H, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF (1999) Distribution of active glycogen synthase kinase 3beta (GSK-3beta) in brains staged for Alzheimer disease neurofibrillary changes. J Neuropathol Exp Neurol 58:1010–1019

    Article  CAS  PubMed  Google Scholar 

  • Planel E, Tatebayashi Y, Miyasaka T, Liu L, Wang LL, Herman M, Yu WH, Luchsinger JA, Wadzinski B, Duff KE, Takashima A (2007) Insulin dysfunction induces in vivo tau hyperphosphorylation through distinct mechanisms. J Neurosci 27:13635–13648

    Article  CAS  PubMed  Google Scholar 

  • Polter AM, Yang S, Jope RS, Li X (2012) Functional significance of glycogen synthase kinase-3 regulation by serotonin. Cell Signal 24:265–271

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rahman A, Khan KM, Al-Khaledi G, Khan I, Al-Shemary T (2012) Over activation of hippocampal serine/threonine protein phosphatases PP1 and PP2A is involved in lead-induced deficits in learning and memory in young rats. NeuroToxicology 1367:1–14

    Google Scholar 

  • Salkovic-Petrisic M, Tribl F, Schmidt M, Hoyer S, Riederer P (2006) Alzheimer like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway. J Neurochem 96:1005–1015

    Article  CAS  PubMed  Google Scholar 

  • Serenó L, Coma M, Rodríguez M, Sánchez-Ferrer P, Sánchez MB, Gich I, Agulló JM, Pérez M, Avila J, Guardia-Laguarta C, Clarimón J, Lleó A, Gómez-Isla T (2009) A novel GSK-3β inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo. Neurobiol Dis 35:359–367

    Article  PubMed  Google Scholar 

  • Sergeant N, Bretteville A, Hamdane M, Caillet-Boudin ML, Grognet P, Bombois S, Blum D, Delacourte A, Pasquier F, Vanmechelen E, Schraen-Maschke S, Buee L (2008) Biochemistry of tau in Alzheimer's disease and related neurological disorders. Exp Rev Proteomics 5:207–224

    Article  CAS  Google Scholar 

  • Sharma M, Gupta YK (2001) Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sci 68:1021–1029

    Article  CAS  PubMed  Google Scholar 

  • Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, Pinkert CA, Amin R, Dhanasekaran M, Suppiramaniam V (2012) Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents. Neurobiol Aging 33:430.e5–430.e18

    Article  CAS  Google Scholar 

  • Uno Y, Iwashita H, Tsukamoto T, Uchiyama N, Kawamoto T, Kori M, Nakanishi A (2009) Efficacy of a novel, orally active GSK-3 inhibitor 6-Methyl-N-[3-[[3-(1-methylethoxy)propyl]carbamoyl]-1Hpyrazol-4-yl]pyridine-3-carboxamide in tau transgenic mice. Brain Res 1296:148–163

    Article  CAS  PubMed  Google Scholar 

  • Wang P, Jiang S, Cui Y, Yue Z, Su C, Sun J, Sheng S, Tian J (2011a) The N-terminal 5-mer peptide analogue P165 of amyloid precursor protein exerts protective effects on SH-SY5Y cells and rat hippocampus neuronal synapses. Neuroscience 173:169–178

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Zou LB, Liu WW, Hao WB, Tashiro S, Onodera S, Ikejima T (2011b) Inhibiting NF-κB activation and ROS production are involved in the mechanism of silibinin's protection against d-galactose-induced senescence. Pharmacol Biochem Behav 98:140–149

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Xia Z, Xu JR, Wang YX, Hou LN, Qiu Y, Chen HZ (2012a) α-Mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates β-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation. Neuropharmacology 62:871–881

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Shen J, Wang J, Lu T, Li C, Zhang X, Liu L, Ding Z (2012b) Lithium attenuates bupivacaine-induced neurotoxicity in vitro through phosphatidylinositol-3-kinase/threonineserine protein kinase b- and extracellular signal regulated kinase-dependent mechanisms. Neuroscience 206:190–200

    Article  CAS  PubMed  Google Scholar 

  • Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, Breitner JCS (2002) Hormone replacement therapy and incidence of Alzheimer disease in older women. JAMA 288:2123–2129

    Article  CAS  PubMed  Google Scholar 

  • Zeng KW, Ko H, Yang HO, Wang XM (2010) Icariin attenuates β-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells. Neuropharmacology 59:542–550

    Article  CAS  PubMed  Google Scholar 

  • Zhang T, Pan BS, Sun GC, Sun X, Sun FY (2010) Diabetes synergistically exacerbates poststroke dementia and tau abnormality in brain. Neurochem Int 56:955–961

    Article  CAS  PubMed  Google Scholar 

  • Zhao QX, Xu Y, Yan WH, Han XF, Xing Y (2011a) The expression and regulation of GSK-3β, CDK-5 and PP2A in differentiated neural stem cells of rats. Life Sci J 8:7–12

    Google Scholar 

  • Zhao RP, Zhang ZX, Song YJ, Wang DS, Qi JP, Wen SR (2011b) Implication of phosphatidylinositol-3 kinase/Akt/glycogen synthase kinase-3β pathway in ginsenoside Rb1's attenuation of beta-amyloid-induced neurotoxicity and tau phosphorylation. J ethnopharmacol 133:1109–1116

    Article  CAS  PubMed  Google Scholar 

  • Zimmer ER, Kalinine E, Haas CB, Torrez VR, Souza DO, Muller AP, Portela LV (2012) Pretreatment with memantine prevents Alzheimer-like alterations induced by intrahippocampal okadaic acid administration in rats. Curr Alzheimer Res 9:1182–1190

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Research Fund for the Doctoral Program of Higher Education (no. 20092134110007) and by National Science and Technology Major Special Project on Major New Drug Innovation of China (no. 2009ZX09103-119 and no. 2009ZX09301-012).

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Authors and Affiliations

  1. Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, People’s Republic of China

    Peng Liu, Li-Bo Zou, Qing Jiao, Tian-Yan Chi, Xue-Fei Ji & Ge Jin

  2. Shenyang Institute of Applied Ecology, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang, Liaoning, 110016, People’s Republic of China

    Li-Hua Wang

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  1. Peng Liu
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Liu, P., Zou, LB., Wang, LH. et al. Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in intracerebroventricular-streptozotocin injected rats. Psychopharmacology 231, 345–356 (2014). https://doi.org/10.1007/s00213-013-3240-4

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