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Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in intracerebroventricular-streptozotocin injected rats.
Psychopharmacology (Berl). 2014 Jan; 231(2):345-56.P

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.

Authors

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Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23958944

Citation

Liu, Peng, et al. "Xanthoceraside Attenuates Tau Hyperphosphorylation and Cognitive Deficits in Intracerebroventricular-streptozotocin Injected Rats." Psychopharmacology, vol. 231, no. 2, 2014, pp. 345-56.
Liu P, Zou LB, Wang LH, et al. Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in intracerebroventricular-streptozotocin injected rats. Psychopharmacology (Berl). 2014;231(2):345-56.
Liu, P., Zou, L. B., Wang, L. H., Jiao, Q., Chi, T. Y., Ji, X. F., & Jin, G. (2014). Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in intracerebroventricular-streptozotocin injected rats. Psychopharmacology, 231(2), 345-56.
Liu P, et al. Xanthoceraside Attenuates Tau Hyperphosphorylation and Cognitive Deficits in Intracerebroventricular-streptozotocin Injected Rats. Psychopharmacology (Berl). 2014;231(2):345-56. PubMed PMID: 23958944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in intracerebroventricular-streptozotocin injected rats. AU - Liu,Peng, AU - Zou,Li-Bo, AU - Wang,Li-Hua, AU - Jiao,Qing, AU - Chi,Tian-Yan, AU - Ji,Xue-Fei, AU - Jin,Ge, PY - 2012/12/03/received PY - 2013/08/05/accepted PY - 2013/8/21/entrez PY - 2013/8/21/pubmed PY - 2015/1/13/medline SP - 345 EP - 56 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 231 IS - 2 N2 - 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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/23958944/Xanthoceraside_attenuates_tau_hyperphosphorylation_and_cognitive_deficits_in_intracerebroventricular_streptozotocin_injected_rats_ L2 - https://dx.doi.org/10.1007/s00213-013-3240-4 DB - PRIME DP - Unbound Medicine ER -