Xanthoceraside attenuates amyloid β peptide25-35-induced learning and memory impairments in mice

Ping Lu, Takayoshi Mamiya, Lingling Lu, Akihiro Mouri, Takashi Ikejima, Hyoung Chum Kim, Li Bo Zou, Toshitaka Nabeshima

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Abstract

Rationale: In Alzheimer's disease (AD), the deposition of amyloid peptides is invariably associated with oxidative stress and inflammatory responses. Xanthoceraside has anti-inflammatory and antioxidative activities. However, it remains unclear whether xanthoceraside improves amyloid β (Aβ)-induced neurotoxicity. Objectives: The purpose of this study was to examine the effect of xanthoceraside on behavioral impairments, inflammatory responses, and oxidative stress induced by Aβ peptide25-35 (Aβ 25-35) in mice. Materials and methods: The mice were treated orally with xanthoceraside (0.02, 0.08, or 0.32 mg/kg, once daily) after the intracerebroventricular injection of Aβ25-35 (day 0). Cognitive functions were evaluated in Y-maze (day 6) and novel object recognition tests (days 7 and 8). Inducible nitric oxide synthase (iNOS) and nitrotyrosine levels in the hippocampus were examined (day 9). The mRNA expressions of iNOS and interleukin-4 (IL-4) in the hippocampus were measured 2 h and 3 days after the Aβ25-35 injection by real-time reverse transcription-polymerase chain reaction. Results: Xanthoceraside significantly attenuated behavioral impairments induced by Aβ25-35 in the Y-maze and novel object recognition tests. Repeated treatment with xanthoceraside significantly inhibited the increase in the expression of iNOS and nitrotyrosine in the hippocampus induced by Aβ25-35, which is associated with an enhanced expression of the IL-4 mRNA. Conclusions: These findings suggest that xanthoceraside attenuates memory impairments through amelioration of oxidative stress and inflammatory responses induced by Aβ25-35 and is a potential candidate for an AD treatment.

Original languageEnglish
Pages (from-to)181-190
Number of pages10
JournalPsychopharmacology
Volume219
Issue number1
DOIs
Publication statusPublished - 01-01-2012

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All Science Journal Classification (ASJC) codes

  • Pharmacology

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