Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in intracerebroventricular-streptozotocin injected rats.
Psychopharmacology (Berl)
; 231(2): 345-56, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-23958944
ABSTRACT
RATIONALE Xanthoceraside, a novel triterpenoid saponin extracted from the fruit husks of Xanthoceras sorbifolia Bunge, reverses cognitive deficits in intracerebroventricular injection of Aß25-35 or Aß1-42 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 ANDMETHODS:
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-3ß (GSK-3ß), 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-3ß (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-3ß signalling pathway and an enhancement of phosphatases activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saponinas
/
Triterpenos
/
Proteínas tau
/
Transtornos Cognitivos
Limite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Ano de publicação:
2014
Tipo de documento:
Article