Cited by 59Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsCholinesterase and Neurodegenerative Diseases

Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model

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Jin, Peng, Kim, Jin-A, Choi, Dong-Young, Lee, Young-Jung, Jung, Heon Sang, Hong, Jin Tae·2013·Journal of Neuroinflammation

Abstract

Background: Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) fibrils within the brain and activation of astrocytes and microglial cells. In this study, we examined anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl)-2-butenal (HPB242), an anti-inflammatory compound produced by the tyrosine-fructose Maillard reaction. Methods: 12-month-old Tg2576 mice were treated with HPB242 (5 mg/kg) for 1 month and then cognitive function was assessed by the Morris water maze test and passive avoidance test. In addition, western blot analysis, Gel electromobility shift assay, immunostaining, immunofluorescence staining, ELISA and enzyme activity assays were used to examine the degree of Aβ deposition in the brains of Tg2576 mice. The Morris water maze task was analyzed using two-way ANOVA with repeated measures. Otherwise were analyzed by one-way ANOVA followed by Dunnett’s post hoc test. Results: Treatment of HPB242 (5 mg/kg for 1 month) significantly attenuated cognitive impairments in Tg2576 transgenic mice. HPB242 also prevented amyloidogenesis in Tg2576 transgenic mice brains. This can be evidenced by Aβ accumulation, BACE1, APP and C99 expression and β-secretase activity. In addition, HPB242 suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes and microglial cells. Furthermore, activation of nuclear factor-kappaB (NF-κB) and signal transducer and activator of transcription 1/3 (STAT1/3) in the brain was potently inhibited by HPB242. Conclusions: Thus, these results suggest that HPB242 might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.

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  • Thiacremonone prevents neuroinflammation and amyloidogenesis by blocking NF-κB activity, and therefore can be used to treat neurodegenerative disorders (e.g., Alzheimer's disease) related to inflammation.

    “Another report indicated that thiacremonone (a sulfur compound isolated from garlic) prevents neuroinflammation and amyloidogenesis by blocking the NF-κB activity, and therefore can be used to treat neurodegenerative disorders (e.g., Alzheimer’s disease) related to inflammation [77].”

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Authors
Jin, P., Kim, J.-A., Choi, D.-Y., Lee, Y.-J., Jung, H. S., & Hong, J. T.
Affiliations
  • Chungbuk National University (KR)
  • Yeungnam University (KR)
  • Cheju Halla University (KR)
Corresponding author
Hong, Jin Tae
Venue
Journal of Neuroinflammation
Published
2013-01-05
Volume
10
Issue
1
Pages
2-2
ISSN
1742-2094 (ISSN-L)
OpenAlex
W2145374150
Cited by
59
References
61
Citations by year
2026: 2 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 3
FWCI
3.95
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Research Foundation
  • National Research Foundation of Korea (2011-0031403, A101836)
  • Ministry of Education, Science and Technology (2011-0031403, A101836)
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
Alzheimer's disease, amyloid-beta, neuroinflammation, Tg2576 mice, cognitive impairment, BACE1, APP, beta-secretase, astrocyte activation, microglial activation, inducible nitric oxide synthase, cyclooxygenase-2, NF-κB, Maillard reaction, neurodegeneration
MeSH terms
Aldehydes, Alzheimer Disease, Animals, Anti-Inflammatory Agents, Non-Steroidal, Disease Models, Animal, Cricetinae, Humans, Mice, Transgenic, Peptide Fragments, Phenols, Amyloid beta-Peptides, Maze Learning, Mice, Plaque, Amyloid

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