Myricetin ameliorates cognitive impairment in 3×Tg Alzheimer's disease mice by regulating oxidative stress and tau hyperphosphorylation.
Biomed Pharmacother
; 177: 116963, 2024 Jun 17.
Article
em En
| MEDLINE
| ID: mdl-38889642
ABSTRACT
BACKGROUND:
Alzheimer's disease is characterized by abnormal ß-amyloid (Aß) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in the protective effect of myricetin.METHODS:
The effect of myricetin was assessed on Aß42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. Behavioral tests were performed to assess the cognitive effects of myricetin (14 days, ip) in 3×Tg mice. The levels of beta-amyloid precursor protein (APP), synaptic and mitochondrial proteins, glycogen synthase kinase3ß (GSK3ß) and extracellular regulated kinase (ERK) 2 were assessed via Western blotting. Flow cytometry assays, immunofluorescence staining, and transmission electron microscopy were used to assess mitochondrial dysfunction and reactive oxidative stress.RESULTS:
We found that, compared with control treatment, myricetin treatment improved spatial cognition and learning and memory in 3×Tg mice. Myricetin ameliorated tau phosphorylation and the reduction in pre- and postsynaptic proteins in Aß42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation, and rescued mitochondrial dysfunction via the associated GSK3ß and ERK 2 signalling pathways.CONCLUSIONS:
This study provides new insight into the neuroprotective mechanism of myricetin in vitro in cell culture and in vivo in a mouse model of Alzheimer's disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Biomed Pharmacother
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China