[Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3β signaling pathway to alleviate Alzheimer's disease mice].

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.

• Authors: Xiao-Min Luo, Bo-Yu Zhang, Yi Ding, Cun-Ping Wang, Qiu-Lin Luo, Rui Tan, Jian Gu, Pu-Yang Gong
• Journal: Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica (Zhongguo Zhong Yao Za Zhi) Vol. 47 Issue 8 Pg. 2074-2081 (Apr 2022) ISSN: 1001-5302 [Print] China
• PMID: 35531723 (Publication Type: Journal Article)

Chemical References

• Plant Extracts
• ershiwuwei shanhu
• tau Proteins
• Aluminum Chloride
• Superoxide Dismutase
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Galactose

Topics

• Aluminum Chloride (adverse effects)
• Alzheimer Disease (drug therapy)
• Animals
• Galactose (adverse effects, metabolism)
• Glycogen Synthase Kinase 3 beta (genetics, metabolism)
• Hippocampus (metabolism)
• Mice
• Mice, Inbred BALB C
• Plant Extracts
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction
• Superoxide Dismutase (metabolism)
• TOR Serine-Threonine Kinases (genetics, metabolism)
• tau Proteins