NeuroDefend, a novel Chinese medicine, attenuates amyloid-β and tau pathology in experimental Alzheimer's disease models

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2020
Contact PI Name:
Min Li
Contact PI Affiliation:
Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
Co-Authors:
A. Iyaswamy, S.K. Krishnamoorthi, J.-X. Song, C.-B. Yang, V. Kaliyamoorthy, H. Zhang, S.G. Sreenivasmurthy, S. Malampati, Z.-Y. Wang, Z. Zhu, B.C.-K. Tong, K.-H. Cheung, J.-H. Lu, S.S.K. Durairajan
Primary Reference (PubMED ID):
31883601
Funding Source:
Hong Kong Health Medical Research Fund
Hong Kong Innovation and Technology Fund
Study Goal and Principal Findings:

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Amyloid-β (Aβ) and hyper-phosphorylated tau accumulation are accountable for the progressive neuronal loss and cognitive impairments usually observed in AD. Currently, medications for AD offer moderate symptomatic relief but fail to cure the disease; hence development of effective and safe drugs is urgently needed for AD treatment. In this study, we investigated a Chinese medicine (CM) formulation named NeuroDefend (ND), for reducing amyloid β (Aβ) and tau pathology in transgenic AD mice models. Regular oral administration of ND improved cognitive function and memory in 3XTg-AD and 5XFAD mice. In addition, ND reduced beta-amyloid precursor protein (APP), APP C-terminal fragments (CTF-β/α), Aβ and 4G8 positive Aβ burden in 3XTg-AD and 5XFAD mice. Furthermore, ND efficiently reduced the levels of insoluble phospho-tau protein aggregates and AT8 positive phospho tau neuron load in 3XTg-AD mice. Hence, ND could be a promising candidate for the treatment of AD in humans.

Bibliographic Notes:
Siva Sundara Kumar Durairajan (Department of Microbiology, Central University of Tamil Nadu, Thiruvarur, India) and Min Li (Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong) are corresponding authors on this paper.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
NeuroDefend
PubMed
Patents
Therapeutic Target:
Multi Target
Therapeutic Notes:
NeuroDefend is a formulation combining modified Huang-Lian-Jie-Du-Tang with 6 herbs: Rhizoma coptidis, Radix scutellariae, Cortex phellodendri, Radix Salviae Miltiorrhizae, Rhizoma Corydalis and Uncaria Rhynchophylla.

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Model Name:
5xFAD
ALZFORUM
Strain/Genetic Background:
C57BL/6
Species:
Mouse
Model Type:
APPxPS1xTau
Model Name:
3xTg
ALZFORUM
Strain/Genetic Background:
C57B6/129SVJ
Animal Model Notes:
C57BL/6 mice, ICR mice and Sprague Dawley rats were used in pharmacokinetic and toxicology studies.

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
Contextual Fear Conditioning
Exploratory Activity
Morris Water Maze
Open Field Test
Motor Function
Locomotor Activity
Path Length
Histopathology
beta Amyloid Deposits
phospho-Tau
Biochemical
Amyloid Precursor Protein (APP)
APP-CTF83 (CTF alpha)
APP-CTF99 (CTF beta)
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Brain-Detergent Soluble beta Amyloid Peptide 40
Brain-Detergent Soluble beta Amyloid Peptide 42
Brain-Formic Acid Soluble beta Amyloid Peptide 40
Brain-Formic Acid Soluble beta Amyloid Peptide 42
PHF Tau
phospho-Tau
Sarkosyl Insoluble Tau
Sarkosyl Soluble Tau
Total Tau Protein
Immunochemistry
Brain-beta Amyloid Deposits
Intracellular beta Amyloid Peptide
phospho-Tau
Microscopy
Cell Count
Spectroscopy
Liquid Chromatography-Mass Spectrometry (LC/MS)
Ultrahigh-Performance Liquid Chromatography with Quadruple Time Of Flight Mass Spectrometry (UHPLC-Q-TOFMS)
Cell Biology
Amyloid Precursor Protein (APP)
APP-CTFs
phospho-Tau
Pharmacokinetics
Area Under the Curve (AUC)
Bioavailability
Clearance (L/h/kg)
Cmax
Drug Concentration-Brain
Drug Concentration-Plasma
Mean Residence Time (MRT)
t1/2 (Elimination Half-Life)
Tmax
Variance of Residence Time (VRT)
Volume of Distribution During Terminal Phase (Vz)
Toxicology
Body Weight
Organ Weight
Organ Histopathology
LD50
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Source URL: http://alzped.nia.nih.gov/neurodefend-novel-chinese