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.
RATIONALE: Xanthoceraside, a novel triterpenoidsaponin 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: S Haege; D Galetzka; U Zechner; T Haaf; M Gamerdinger; C Behl; C Hiemke; U Schmitt Journal: Neuropsychobiology Date: 2010-03-19 Impact factor: 2.328
Authors: Brian C Shonesy; Kariharan Thiruchelvam; Kodeeswaran Parameshwaran; Engy Abdel Rahman; Senthilkumar S Karuppagounder; Kevin W Huggins; Carl A Pinkert; Rajesh Amin; Muralikrishnan Dhanasekaran; Vishnu Suppiramaniam Journal: Neurobiol Aging Date: 2011-01-21 Impact factor: 4.673
Authors: Kurt R Brunden; Carlo Ballatore; Alex Crowe; Amos B Smith; Virginia M-Y Lee; John Q Trojanowski Journal: Exp Neurol Date: 2009-09-08 Impact factor: 5.330