Qingxin kaiqiao fang ameliorates memory impairment and inhibits apoptosis in APP/PS1 double transgenic mice through the MAPK pathway.
Drug Des Devel Ther
; 13: 459-475, 2019.
Article
em En
| MEDLINE
| ID: mdl-30774310
ABSTRACT
BACKGROUND:
Qingxin kaiqiao fang (QKF) has been found to treat Alzheimer's disease (AD) through apoptosis inhibition. The mitogen-activated protein kinase (MAPK) pathway is closely related to apoptosis in the course of AD. This study aimed to investigate whether QKF-induced apoptosis depression is achieved through MAPK pathway. MATERIALS ANDMETHODS:
C57BL/6 J and APP/PS1 mice were used as control and model groups. APP/PS1 mice were treated with different dosages of QKF (4.75, 9.5, and 19 gâ kg-1â d-1â ig, respectively) for 12 weeks as L-QKF, M-QKF, and H-QKF groups. The M-QKF-treated APP/ PS1 mice were administrated with 2 µg/kg of U46619 and saline, intra ventricular ventricle injection, as M-QKF+U46619 and M-QKF+saline groups and were injected with PD98059 0.3 mg/kg and the same volume of dimethyl sulfoxide (DMSO), intravenous, as M-QKF+PD98059 and M-QKF+DMSO groups. After 12 weeks treatment, Morris water maze was performed for behavior study. Pathological degeneration was examined by H&E staining, Nissl staining, and transmission electron microscope observation of hippocampus; immunohistochemistry and Western blot (WB) were tested for amyloid ß (Aß) expression. Apoptosis was measured through TUNEL assay; Bax, Bcl-2, and caspase-3 expression through WB; and cleaved caspase-3 expression through ELISA. MAPK pathway was detected via WB for the expressions of ERK1/2, JNK, and p38 MAPK and their phosphorylation patterns.RESULTS:
QKF improved the learning and memory capability, as well as inhibited neuronal apoptosis and then reduced the pathological degeneration of APP/PS1 mice. M-QKF reduced neuron apoptosis by inhibiting p38 MAPK and activating ERK1/2 but had no significant effect on JNK.CONCLUSION:
QKF, especially at the middle dose, alleviated the learning and memory impairment and played an antiapoptotic role in AD through MAPK pathways.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Medicamentos de Ervas Chinesas
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Apoptose
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Proteínas Quinases Ativadas por Mitógeno
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Doença de Alzheimer
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Transtornos da Memória
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article