The effects of festidinol treatment on the D-galactose and aluminum chloride-induced Alzheimer-like pathology in mouse brain.
Phytomedicine
; 98: 153925, 2022 Apr.
Article
en En
| MEDLINE
| ID: mdl-35104759
ABSTRACT
BACKGROUND:
Festidinol is a flavan-3-ol which has been shown to reduce advanced glycation end products (AGEs) and reactive oxygen species, both of which play a crucial role in the pathology of many neurodegenerative diseases.PURPOSE:
This study aimed to investigate the effects of festidinol on oxidative stress, amyloidogenesis, phosphorylated tau (pTau) expression, synaptic function, and cognitive impairment, and the potential mechanisms involved, in a mouse model with an Alzheimer-like pathology.METHODS:
D-galactose (150 mg/kg) and aluminum chloride (10 mg/kg) were injected intraperitoneally into 40 mice for 90 days to generate an AD mouse model with cognitive impairment. Festidinol (30 mg/kg) and donepezil (5 mg/kg) were then administered orally for 90 days after which behavior and molecular changes in the brain were measured.RESULTS:
The aluminum accumulated and the expression of the cell senescence marker P16 increased after exposure to D-galactose and AlCl3 (2.5 ± 0.5 mg/kg, 149.1 ± 28.1% of control, respectively). Festidinol markedly decreased the escape latency (8.7 ± 4.3 s) and increased the number of platform crossings (8 ± 1.4 time) in the Morris water maze test. Superoxide dismutase activity was significantly elevated after festidinol administration, however there were significant reductions in the levels of 4hydroxy-2-nonenal, receptor for advanced glycation end products, phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (pNF-κB), and nuclear factor of activated T cells 1 (NFAT1). Festidinol attenuated amyloid beta production by reducing the mRNA of beta-site APP cleaving enzyme 1 (BACE1). Festidinol also significantly decreased the expression of pTau and phosphorylated glycogen synthase kinase 3 (148.6 ± 37.6% of control, 125.3 ± 22.6% of control, respectively).CONCLUSION:
Festidinol can ameliorate learning and memory impairments by modulating amyloidogenesis, tau hyperphosphorylation, cholinergic activity, neuroinflammation, and oxidative stress, and by regulating the brain-derived neurotrophic factor signaling pathway.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Phytomedicine
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2022
Tipo del documento:
Article
País de afiliación:
Tailandia