Baicalein reduces β-amyloid and promotes nonamyloidogenic amyloid precursor protein processing in an Alzheimer’s disease transgenic mouse model

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2013
Contact PI Name:
Jun Tan
Contact PI Affiliation:
Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
Co-Authors:
She-Qing Zhang, Demian Obregon, Jared Ehrhart, Juan Deng, Jun Tian, Huayan Hou, Brian Giunta, Darrell Sawmiller
Primary Reference (PubMED ID):
23686791
Funding Source:
National Institute on Aging (NIA)
Science and Technology Commission of Shanghai Municipality
Study Goal and Principal Findings:

Baicalein, a flavonoid isolated from the roots of Scutellaria baicalensis, is known to modulate γ-aminobutyric acid (GABA) type A receptors. Given prior reports demonstrating benefits of GABAA modulation for Alzheimer’s disease (AD) treatment, we wished to determine whether this agent might be beneficial for AD. CHO cells engineered to overexpress wild-type amyloid precursor protein (APP), primary culture neuronal cells from AD mice (Tg2576) and AD mice were treated with baicalein. In the cell cultures, baicalein significantly reduced the production of β-amyloid (Aβ) by increasing APP α-processing. These effects were blocked by the GABAA antagonist bicuculline. Likewise, AD mice treated daily with i.p. baicalein for 8 weeks showed enhanced APP α-secretase processing, reduced Aβ production, and reduced AD-like pathology together with improved cognitive performance. Our findings suggest that baicalein promotes nonamyloidogenic processing of APP, thereby reducing Aβ production and improving cognitive performance, by activating GABAA receptors.

Bibliographic Notes:
She-Qing Zhang (Department of Neurology, Changhai Hospital, Shanghai, China) and Jun Tan (Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA) are corresponding authors on this paper.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
Baicalein
PubMed
PubChem
DrugBank
ClinicalTrials
Patents
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Model Name:
Tg2576
ALZFORUM
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
Experiment Notes

Inclusion/Exclusion Criteria: Two animals in the baicalein treatment group were eliminated from the final data analysis because of a consistent lack of arm choices throughout the test period.

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Radial Arm Water Maze
Biochemical
Brain-Detergent Soluble beta Amyloid Peptide 40
Brain-Detergent Soluble beta Amyloid Peptide 42
Brain-Guanidine Soluble beta Amyloid Peptide 40
Brain-Guanidine Soluble beta Amyloid Peptide 42
Amyloid Precursor Protein (APP)
APP-CTF99 (CTF beta)
Soluble Amyloid Precursor Protein alpha (sAPP alpha)
Cell Biology
beta Amyloid Peptide Secretion
Soluble Amyloid Precursor Protein alpha (sAPP alpha) Secretion
APP-CTFs
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Source URL: http://alzped.nia.nih.gov/baicalein-reduces-β-amyloid