Erzhi pills ameliorate cognitive dysfunction and alter proteomic hippocampus profiles induced by d-galactose and Aß1-40 injection in ovariectomized Alzheimer's disease model rats.
Pharm Biol
; 59(1): 1402-1414, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34672897
ABSTRACT
CONTEXT Erzhi pills are a classic Chinese medicine prescription, but their effects on Alzheimer's disease (AD) are not clear. OBJECTIVE:
The protective effects of Erzhi pills in AD rats and their potential mechanisms were investigated. MATERIALS ANDMETHODS:
An AD rat model was established by ovariectomy combined with d-galactose and Aß1-40 injection. Rats were randomly divided into five groups sham-operated, model, oestradiol valerate (0.80 mg/kg), Erzhi pills high-dose (1.50 g/kg), and Erzhi pills low-dose (0.75 g/kg). Learning and memory abilities were evaluated with the Morris water maze test, oestrogen levels with an ELISA kit, and hippocampal neuron morphology and Nissl bodies in the cytoplasm with H&E and Nissl staining. The expression of ERß, Aß1-40, and p-tau404 was determined by immunohistochemistry. Nano LC-LTQ-Orbitrap Proteomics determined potential targets and related signalling pathways. Western blotting was used to detect the expression of the related proteins.RESULTS:
Erzhi pills (1.5, 0.75 g/kg) markedly reduced escape latencies on the MWM, increased numbers of platform crossings, numbers of neurons, Nissl bodies, oestrogen levels (100.18, 43.04 pg/mL), and ERß-positive cells (57.42, 39.83); Aß1-40 (18.85, 36.83)- and p-tau404 (14.42, 29.71)-positive cells were significantly decreased. Proteomics identified more than 100 differentially expressed proteins involved in 48 signalling pathways, five of which are involved in the PI3K/Akt signalling pathway. Western blotting showed decreased expression of GSK3ß and Bad, while Akt, PI3K, 14-3-3, Bcl-xl, and Bcl-2 were upregulated. DISCUSSION ANDCONCLUSION:
Erzhi pills may serve as a potential agent for AD therapeutics by improving learning and memory.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Medicamentos de Ervas Chinesas
/
Doença de Alzheimer
/
Disfunção Cognitiva
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China