Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3β signaling pathway to alleviate Alzheimer's disease mice / 中国中药杂志

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.

Evaluation of Glucosamine Effect Against Heart and Brain Damage Induced by Y-radiation or Aluminium Chloride in Female Rats

Abstract Glucosamine is known as anti-inflammatory, antioxidant and as neuroprotective as well as using to treat many of diseases. This work aimed to investigate the remedial effect of glucosamine (20mg/kg b.wt) against the damage induced by a single dose of γ-radiation (8Gy) or aluminium chloride (AlCl3) (100mg/kg b.wt) in the heart and brain tissues of female rats. Serum aspartate aminotransferase (AST), cholesterol, triglycerides (TGs), LDH and creatine kinase (CPK) were measured. Moreover, gene expression of amyloid protein precursor (APP) and seladin-1 were estimated in the brain tissue. Also, acetylcholinesterase activity (AChE) and p-tau protein expression were estimated in brain homogenate. Metallothioneine (MT) was estimated in the heart and brain tissues. Heart and brain histopathological examination was performed. Irradiation significantly decreased serum AST, CPK and LDH, as well as MT levels in heart and brain tissues. Also, gene expression of seladin-1 decreased. On the other hand, irradiation significantly increased serum TGs level and brain AchE activity, tau protein, and β-amyloid percursor (APP). AlCl3 administration (21 days) induced disturbance in most of the estimated parameters, especially AST, TGs, and MT. Glucosamine treatment with irradiation or AlCl3 improved most of the measured parameters. In addition, histopathological examination confirmed the biochemical results. In conclusion: Glucosamine could be used to improve the heart and brain damages induced by γ-radiation exposure or AlCl3.