Fuzhisan ameliorates the memory deficits in aged SAMP8 mice via decreasing Aβ production and tau hyperphosphorylation of the hippocampus


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2016
Contact PI Name:
Yan-Bing Li
Contact PI Affiliation:
Department of Neurology, The Shandong Province, Qianfoshan Hospital, Jinan, China
Co-Authors:
Zhao-Xu Zhang, Rui-Ping Zhao, De-Sheng Wang
Primary Reference (PubMED ID):
Funding Source:
National Natural Science Foundation of China
Study Goal and Principal Findings:

The pathological features of Alzheimer’s disease (AD) include extracellular neuritic plaques containing β-amyloid (Aβ) peptide, a cleaved fragment of amyloid precursor protein (APP) via β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Cyclin-dependent kinase 5 (Cdk5) is increasingly thought to play a pivotal role in the pathogenesis of AD, both as a regulator of the production of Aβ and through its well-established role as a tau kinase. Fuzhisan (FZS), a Chinese herbal complex prescription, has been used for the treatment AD for over 20 years, and is known to enhance the cognitive ability in AD patients as well as in AD model rats. To investigate mechanisms of AD and the potential therapy of FZS in AD, we treated senescence-accelerated mouse SAMP8 mice, a useful model of AD-related memory impairment, with FZS by intragastrical administration for 8 weeks and Donepizel was used as a positive control. The results showed that FZS (0.3, 0.6, and 1.2 g/kg/day) improved impaired cognitive ability of aged SAMP8 mice in a dose-dependent manner. FZS robustly decreased Aβ level and phosphorylation of tau. This was accompanied by a significant decrease in the BACE1 level and phosphorylated APP (Thr668). Futhermore, the p25/Cdk5 pathway was markedly down-regulated by FZS treatment. These results indicated that the memory ameliorating effect of FZS may be, in part, by regulation the p25/Cdk5 pathway which may contribute to down-regulation of Aβ and tau hyperphosphorylation.

Bibliographic Notes:
Zhao-Xu Zhang and Yan-Bing Li (Department of Neurology, The Shandong Province, Qianfoshan Hospital, Jinan, China) are corresponding authors on this paper.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
Fuzhisan
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
Accelerated Aging
Strain/Genetic Background:
Not Reported
Species:
Mouse
Model Type:
Accelerated Aging Resistant
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Biochemical
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
APP-CTF99 (CTF beta)
phospho-Amyloid Precursor Protein (phospho-APP)
beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)
Cyclin-Dependent Kinase 5 (CDK5)
Cyclin-Dependent Kinase 5 (CDK5) Activity
p25/p35/Cyclin-Dependent Kinase 5 Regulatory Subunit 1 (CDK5R1)
Total Tau Protein
phospho-Tau

Source URL: http://alzped.nia.nih.gov/fuzhisan-ameliorates-memory