Neuroprotection of macamide in a mouse model of Alzheimer's disease involves Nrf2 signaling pathway and gut microbiota.
Eur J Pharmacol
; 975: 176638, 2024 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-38734297
ABSTRACT
The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique ingredients in maca. Improvement effects and mechanisms of macamide on cognitive impairment have not been revealed. In this study, Vina 1.1.2 was used for docking to evaluate the binding abilities of 12 main macamides to acetylcholinesterase (AChE). N-benzyl-(9Z,12Z)-octadecadienamide (M 182) was selected to study the following experiments because it can stably bind to AChE with a strong binding energy. The animal experiments showed that M 182 prevented the scopolamine (SCP)-induced cognitive impairment and neurotransmitter disorders, increased the positive rates of Nrf2 and HO-1 in hippocampal CA1, improved the synaptic plasticity by maintaining synaptic morphology and increasing the synapse density. Moreover, the contents of IL-1ß, IL-6, and TNF-α in the hippocampus, serum, and colon were reduced by M 182. Furthermore, M 182 promoted colonic epithelial integrity and partially restored the composition of the gut microbiota to normal, including decreased genera Clostridiales_unclassified and Lachnospiraceae_unclassified, as well as increased genera Muribaculaceae_unclassified, Muribaculum, Alistipes, and Bacteroides, which may be the possible biomarkers of cognitive aging. In summary, M 182 exerted neuroprotective effects on SCP-induced AD mice possibly via activating the Nrf2/HO-1 signaling pathway and modulating the gut microbiota.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fármacos Neuroprotetores
/
Modelos Animais de Doenças
/
Fator 2 Relacionado a NF-E2
/
Doença de Alzheimer
/
Microbioma Gastrointestinal
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China