(-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer's disease model mice by upregulating neprilysin expression


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2015
Contact PI Name:
Qi Wang
Contact PI Affiliation:
DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chines Medicine, Guangdong Province, China
Co-Authors:
Xiang Chang, Cuiping Rong, Yunbo Chen, Cong Yang, Qian Hu,Yousheng Mo, Chunxia Zhang, Xiaoqiong Gu, Lei Zhang, Wenqing He, Shuy Cheng, Xueqin Hou, Ruyu Su, Sijun Liu, Wenjun Dun, Shuhuan Fang
Primary Reference (PubMED ID):
Funding Source:
National Natural Science Foundation of China
Study Goal and Principal Findings:

Epigenetic changes are involved in learning and memory, and histone deacetylase (HDAC) inhibitors are considered potential therapeutic agents for Alzheimer's disease (AD). We previously reported that (-)-epigallocatechin-3-gallate (EGCG) acts as an HDAC inhibitor. Here, we demonstrate that EGCG reduced β-amyloid (Aβ) accumulation in vitro and rescued cognitive deterioration in senescence-accelerated mice P8 (SAMP8) via intragastric administration of low- and high-dose EGCG (5 and 15 mg/kg, respectively) for 60 days. The AD brain has decreased levels of the rate-limiting degradation enzyme of Aβ, neprilysin (NEP). We found an association between EGCG-induced reduction in Aβ accumulation and elevated NEP expression. Further, NEP silencing prevented the EGCG-induced Aβ downregulation. Our findings suggest that EGCG might be effective for treating AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Dietary Supplement
Therapeutic Agent:
(-)-Epigallocatechin-3-gallate
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
Accelerated Aging Resistant
Strain/Genetic Background:
Not Reported
Species:
Mouse
Model Type:
Accelerated Aging
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
Neprilysin
Brain-beta Amyloid Peptide 42
Bcl-2
Amyloid Precursor Protein (APP)
Bax
Cell Biology
Cell Proliferation
Microscopy
Cell Survival

Source URL: http://alzped.nia.nih.gov/epigallocatechin-3-gallate