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Xanthoceraside attenuates learning and memory deficits via improving insulin signaling in STZ-induced AD rats.

Abstract
Xanthoceraside, a triterpenoid saponin extracted from the fruit husks of Xanthoceras sorbifolia Bunge, has been shown to reverse the cognitive deficits observed in several Alzheimer's disease (AD) animal models. Increasing evidence suggests the involvement of the insulin signaling pathway in neurodegenerative disorders such as AD. Thus, we used an AD animal model of cognitive impairment induced by the intracerebroventricular (ICV) injection of streptozotocin (STZ) to test the effects of xanthoceraside on behavioral impairments and insulin signaling mechanisms. In our present study, memory impairment was assessed using the Morris water maze test. The expression of IR, IGF-1R and Raf-1/ERK/CREB was tested by western blotting. The STZ group showed memory deficits in the Morris water maze test and significant decreases in IR and IGF-1R protein levels in the hippocampus. Xanthoceraside treatment significantly rescued memory deficits, as well as IR and IGF-1R protein expression levels. STZ inhibited the Ras/ERK signaling cascade and decreased the phosphorylation of CREB; these effects were also attenuated by xanthoceraside treatment. These results suggest the potential use of xanthoceraside for the treatment of neurodegenerative disorders in which brain insulin signaling may be involved.
AuthorsPeng Liu, Libo Zou, Qing Jiao, Tianyan Chi, Xuefei Ji, Yue Qi, Qian Xu, Lihua Wang
JournalNeuroscience letters (Neurosci Lett) Vol. 543 Pg. 115-20 (May 24 2013) ISSN: 1872-7972 [Electronic] Ireland
PMID23562514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Cyclic AMP Response Element-Binding Protein
  • Insulin
  • Saponins
  • Triterpenes
  • xanthoceraside
  • Streptozocin
  • Receptor, IGF Type 1
  • Receptor, Insulin
  • Proto-Oncogene Proteins c-raf
  • Extracellular Signal-Regulated MAP Kinases
Topics
  • Alzheimer Disease (psychology)
  • Animals
  • Cyclic AMP Response Element-Binding Protein (metabolism)
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Female
  • Hippocampus (metabolism)
  • Injections, Intraventricular
  • Insulin (physiology)
  • Learning Disabilities (chemically induced, drug therapy, metabolism)
  • Male
  • Maze Learning (drug effects)
  • Memory Disorders (chemically induced, drug therapy, metabolism)
  • Phosphorylation
  • Proto-Oncogene Proteins c-raf (metabolism)
  • Rats
  • Rats, Wistar
  • Receptor, IGF Type 1 (metabolism)
  • Receptor, Insulin (metabolism)
  • Saponins (pharmacology, therapeutic use)
  • Signal Transduction
  • Streptozocin (administration & dosage)
  • Triterpenes (pharmacology, therapeutic use)

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