TY - JOUR
T1 - Xanthoceraside attenuates amyloid β peptide25-35-induced learning and memory impairments in mice
AU - Lu, Ping
AU - Mamiya, Takayoshi
AU - Lu, Lingling
AU - Mouri, Akihiro
AU - Ikejima, Takashi
AU - Kim, Hyoung Chum
AU - Zou, Li Bo
AU - Nabeshima, Toshitaka
N1 - Funding Information:
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).
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s00213-011-2386-1
DO - 10.1007/s00213-011-2386-1
M3 - Article
C2 - 21735075
AN - SCOPUS:84856643383
VL - 219
SP - 181
EP - 190
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 1
ER -