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1.
Phytomedicine ; 118: 154930, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37348246

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid-ß (Aß) and excessive neuroinflammation, resulting in neuronal cell death and cognitive impairments. Eugenol, a phenylpropene, is the main component of Syzygium aromaticum L. (Myrtaceae) and has multiple therapeutic effects, including neuroprotective and anti-inflammatory effects, through multimodal mechanisms. PURPOSE: We aimed to investigate the effect of eugenol on AD pathologies using a 5× familiar AD (5×FAD) mouse model. METHODS: Eight-month-old 5×FAD and wild-type mice were administered with eugenol (10 or 30 mg/kg/day, p.o) for 2 months. Y-maze and Morris water maze tests were performed to assess the cognitive function of mice. After the behavioral test, molecular analysis was conducted to investigate the therapeutic mechanism of eugenol. RESULTS: Our findings indicate that eugenol treatment effectively mitigated cognitive impairments in 5×FAD mice. This beneficial effect was associated with a decrease in AD pathologies, including neuronal cell loss and Aß deposition. Specifically, eugenol inhibited necroptosis activation and increased microglial phagocytosis, which were the underlying mechanisms for the observed reductions in neuronal cell loss and Aß deposition, respectively. CONCLUSION: Overall, our data suggest that eugenol would be a potential therapeutic candidate for AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Camundongos , Animais , Doença de Alzheimer/metabolismo , Eugenol/farmacologia , Eugenol/uso terapêutico , Camundongos Transgênicos , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças
2.
Int J Mol Sci ; 21(12)2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32599846

RESUMO

Abnormal amyloid-ß (Aß) accumulation is the most significant feature of Alzheimer's disease (AD). Among the several secretases involved in the generation of Aß, ß-secretase (BACE1) is the first rate-limiting enzyme in Aß production that can be utilized to prevent the development of Aß-related pathologies. Cinnamon extract, used in traditional medicine, was shown to inhibit the aggregation of tau protein and Aß aggregation. However, the effect of trans-cinnamaldehyde (TCA), the main component of cinnamon, on Aß deposition is unknown. Five-month-old 5XFAD mice were treated with TCA for eight weeks. Seven-month-old 5XFAD mice were evaluated for cognitive and spatial memory function. Brain samples collected at the conclusion of the treatment were assessed by immunofluorescence and biochemical analyses. Additional in vivo experiments were conducted to elucidate the mechanisms underlying the effect of TCA in the role of Aß deposition. TCA treatment led to improvements in cognitive impairment and reduced Aß deposition in the brains of 5XFAD mice. Interestingly, the levels of BACE1 were decreased, whereas the mRNA and protein levels of three well-known regulators of BACE1, silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC1α), and PPARγ, were increased in TCA-treated 5XFAD mice. TCA led to an improvement in AD pathology by reducing BACE1 levels through the activation of the SIRT1-PGC1α-PPARγ pathway, suggesting that TCA might be a useful therapeutic approach in AD.


Assuntos
Acroleína/análogos & derivados , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismo , Acroleína/farmacologia , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Animais , Antimutagênicos/farmacologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , PPAR gama/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Sirtuína 1/genética
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