Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3β signaling pathway to alleviate Alzheimer's disease mice.
10.19540/j.cnki.cjcmm.20220127.701
- Author:
Xiao-Min LUO
1
;
Bo-Yu ZHANG
1
;
Yi DING
1
;
Cun-Ping WANG
1
;
Qiu-Lin LUO
1
;
Rui TAN
2
;
Jian GU
1
;
Pu-Yang GONG
1
Author Information
1. School of Pharmacy, Southwest Minzu University Chengdu 610041, China.
2. College of Life Science and Engineering, Southwest Jiaotong University Chengdu 610031, China.
- Publication Type:Randomized Controlled Trial, Veterinary
- Keywords:
Alzheimer′s disease;
D-galactose;
Ershiwuwei Shanhu Pills;
aluminum chloride
- MeSH:
Aluminum Chloride/adverse effects*;
Alzheimer Disease/drug therapy*;
Animals;
Galactose/metabolism*;
Glycogen Synthase Kinase 3 beta/metabolism*;
Hippocampus/metabolism*;
Mice;
Mice, Inbred BALB C;
Plant Extracts;
Proto-Oncogene Proteins c-akt/metabolism*;
Signal Transduction;
Superoxide Dismutase/metabolism*;
TOR Serine-Threonine Kinases/metabolism*;
tau Proteins
- From:
China Journal of Chinese Materia Medica
2022;47(8):2074-2081
- CountryChina
- Language:Chinese
-
Abstract:
The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.
