Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2013-01-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://www.jneuroinflammation.com/content/10/1/2 |
| _version_ | 1831538015775752192 |
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| author | Jin Peng Kim Jin-A Choi Dong-Young Lee Young-Jung Jung Heon Sang Hong Jin Tae |
| author_facet | Jin Peng Kim Jin-A Choi Dong-Young Lee Young-Jung Jung Heon Sang Hong Jin Tae |
| author_sort | Jin Peng |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-16T23:16:31Z |
| format | Article |
| id | doaj.art-37f98fd861fa4114ac923fd3923a715f |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-16T23:16:31Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-37f98fd861fa4114ac923fd3923a715f2022-12-21T22:12:16ZengBMCJournal of Neuroinflammation1742-20942013-01-01101210.1186/1742-2094-10-2Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice modelJin PengKim Jin-AChoi Dong-YoungLee Young-JungJung Heon SangHong Jin Tae<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.jneuroinflammation.com/content/10/1/2Alzheimer’s diseaseAmyloid-betaNF-κBSTAT1/32,4-bis(p-hydroxyphenyl)-2-butenal |
| spellingShingle | Jin Peng Kim Jin-A Choi Dong-Young Lee Young-Jung Jung Heon Sang Hong Jin Tae Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model Journal of Neuroinflammation Alzheimer’s disease Amyloid-beta NF-κB STAT1/3 2,4-bis(p-hydroxyphenyl)-2-butenal |
| title | Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model |
| title_full | Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model |
| title_fullStr | Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model |
| title_full_unstemmed | Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model |
| title_short | Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s disease mice model |
| title_sort | anti inflammatory and anti amyloidogenic effects of a small molecule 2 4 bis p hydroxyphenyl 2 butenal in tg2576 alzheimer s disease mice model |
| topic | Alzheimer’s disease Amyloid-beta NF-κB STAT1/3 2,4-bis(p-hydroxyphenyl)-2-butenal |
| url | http://www.jneuroinflammation.com/content/10/1/2 |
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