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2,2',4'-trihydroxychalcone from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory impairment in mice


Year of Publication:
Contact PI Name:
Hu Lihong
Contact PI Affiliation:
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai, China.
Z. Zhu, C. Li, X. Wang, Z. Yang, J. Chen, H. Jiang, X. Shen
Primary Reference (PubMED ID):
Funding Source:
Major Program of National Natural Science Foundation of China
Major State Basic Research Development Program of China
Key New Drug Creation and Development Program of China
Study Goal and Principal Findings:

Alzheimer's disease (AD) characterizes a progressive neurodegenerative disorder of the brain, while AD patients are afflicted with irreversible loss of neurons and further the intellectual abilities including memory and reasoning. One of the typical hallmarks of AD is the deposition of senile plaque that is contributed mainly by amyloid-beta (Abeta), whose production is initiated by beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1). Inhibition of BACE1 is thereby regarded as an attractive strategy for anti-AD drug discovery. Here, was reported that the natural product 2,2',4'-trihydroxychalcone (TDC) from Glycyrrhiza glabra functioned as a specific non-competitive inhibitor against BACE1 enzyme, and potently repressed beta-cleavage of APP and production of Abeta in human embryo kidney cells-APPswe cells. Moreover, the amelioration ability of this compound against the in vivo memory impairment was further evaluated by APP-PS1 double transgenic mice model. It is discovered that treatment of 9 mg/kg/day of TDC could obviously decrease Abeta production and Abeta plaque formation, while efficiently improve the memory impairment based on Morris water maze test. This findings thus demonstrated that the natural product TDC as a new BACE1 inhibitor could ameliorate memory impairment in mice, and is expected to be potentially used as a lead compound for further anti-AD reagent development.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
2,2',4'-trihydroxychalcone (TDC)
Therapeutic Target:

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:

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
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


Outcome Measured
Outcome Parameters
Morris Water Maze
beta Amyloid Deposits
beta Amyloid Load
Dense-core/Compact Plaques
Intracellular beta Amyloid Peptide
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Soluble Amyloid Precursor Protein beta (sAPP beta)
Amyloid Precursor Protein (APP)
APP-CTF99 (CTF beta)
beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)
alpha Secretase Activity
gamma Secretase Activity
Amyloid Precursor Protein (APP) mRNA
beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Activity
beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) mRNA
Cell Biology
Cell Viability
Target Engagement (Reduction beta Amyloid Peptides-Brain)