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

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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 (Aβ25–35) 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.

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Abbreviations

Aβ:

Amyloid β

Aβ25–35 :

Amyloid β peptide25–35

Aβ35–25 :

Amyloid β peptide35–25

AD:

Alzheimer’s disease

Ct:

Threshold cycles

i.c.v.:

Intracerebroventricularly

IL-1β:

Interleukin-1β

IL-4:

Interleukin-4

iNOS:

Inducible nitric oxide synthase

LTP:

Long-term potentiation

NO:

Nitric oxide

p.o.:

Per os

RT-PCR:

Reverse transcription-polymerase chain reaction

SDS:

Sodium dodecyl sulfate

TNF-α:

Tumor necrosis factor-α

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Acknowledgments

This study was supported by Grants-in-aid for Scientific Research (A) (22248033), Scientific Research (B) (20390073, 21390045), and Exploratory Research (19659017, 22659213); and the joint research project of the Japan-Korea basic scientific cooperation program from JSPS; by the “Academic Frontier” Project for Private Universities (2007–2011) and by a Regional Joint Research Program supported by grants to Private Universities to Cover Current Expenses from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); by Research on Regulatory Science of Pharmaceuticals and Medical Devices; and by Research on Risk of Chemical Substances, Health and Labour Science Research Grants supported by the Ministry of Health, Labour and Welfare, Japan (MHLW).

Statement of conflicts of interest

The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan

    Ping Lu, Takayoshi Mamiya, Lingling Lu, Akihiro Mouri & Toshitaka Nabeshima

  2. Comparative Cognitive Science Institutes, Meijo University, Nagoya, 468-8503, Japan

    Akihiro Mouri & Toshitaka Nabeshima

  3. China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Takashi Ikejima

  4. Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 200-701, South Korea

    Hyoung-Chum Kim

  5. Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China

    Li-Bo Zou

  6. Japanese Drug Organization of Appropriate Use and Research, Nagoya, 468-0077, Japan

    Toshitaka Nabeshima

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  1. Ping Lu
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  2. Takayoshi Mamiya
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  8. Toshitaka Nabeshima
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Correspondence to Li-Bo Zou or Toshitaka Nabeshima.

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Lu, P., Mamiya, T., Lu, L. et al. Xanthoceraside attenuates amyloid β peptide25–35-induced learning and memory impairments in mice. Psychopharmacology 219, 181–190 (2012). https://doi.org/10.1007/s00213-011-2386-1

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  • DOI: https://doi.org/10.1007/s00213-011-2386-1

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