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WS-5 extract of Curcuma longa, Chaenomeles sinensis, and Zingiber officinale contains anti-AChE compounds and improves β-amyloid-induced memory impairment in mice

Bibliographic

Year of Publication:
2019
Contact PI Name:
JaeYoon Leem
Contact PI Affiliation:
College of Pharmacy, Woosuk University, Wanju, Jeonbuk, Republic of Korea
Co-Authors:
Ju Eun Kim, Abinash Chandra Shrestha, Hyo Shin Kim, Ha Neul Ham, Jun Hyeong Kim,1 Yeong Jee Kim, Yun Jeong Noh, Su Jin Kim, Dae Keun Kim, Hyung Kwon Jo, Dae Sung Kim, Kwang Hyun Moon, Jeong Ho Lee, Kyung Ok Jeong
Primary Reference (PubMED ID):
Funding Source:
Not Reported
Study Goal and Principal Findings:

Alzheimer's disease (AD) is linked to an extensive neuron loss via accumulation of amyloid-beta (Aβ) as senile plaques associated with reactive astrocytes and microglial activation in the brain. The objective of this study was to assess the therapeutic effect of WS-5 ethanol extract in vitro and in vivo against Aβ-induced AD in mice and to identify the extract's active constituents. In the present study, WS-5 exerted a significant inhibitory effect on acetylcholinesterase (AChE). Analysis by transmission electron microscopy (TEM) revealed that WS-5 prevented Aβ oligomerization via inhibition of Aβ 1-42 aggregation. Evaluation of antioxidant activities using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) demonstrated that WS-5 possessed a high antioxidant activity, which was confirmed by measuring the total antioxidant status (TAS). Furthermore, the anti-inflammatory properties of WS-5 were examined using lipopolysaccharide-stimulated BV-2 microglial cells. WS-5 significantly inhibited the lipopolysaccharide-induced production of nitric oxide and two proinflammatory cytokines, TNF-α and IL-6. The memory impairment in mice with Aβ-induced AD was studied using the Morris water maze and passive avoidance test. Immunohistochemistry was performed to monitor pathological changes in the hippocampus and cortex region of the mouse brain. The animal study showed that WS-5 (250 mg/kg) treatment improved learning and suppressed memory impairment as well as reduced Aβ plaque accumulation in Aβ-induced AD. HPLC analysis identified the extract's active compounds that exert anti-AChE activity. In summary, our findings suggest that WS-5 could be applied as a natural product therapy with a focus on neuroinflammation-related neurodegenerative disorders.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
WS-5
Therapeutic Target:
Multi Target
Therapeutic Notes:
WS-5, a 45% ethanol extract of a mixture of three traditional medicinal plant materials, is prepared using the rhizome of Curcuma longa L. (turmeric), the fruits of Chaenomeles sinensis Koehne (Chinese quince), and the dried rhizome of Zingiber officinale Roscoe (ginger) at a ratio of 2:1.5:1.

Animal Model

Model Information:
Species:
Mouse
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:
ICR

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
Passive Avoidance Test
Morris Water Maze
Histopathology
beta Amyloid Load
beta Amyloid Deposits
Biochemical
Acetylcholinesterase (AChE) Activity
Total Antioxidant Capacity (TAC)
Antioxidative Activity
Tumor Necrosis Factor alpha (TNF alpha)
Interleukin 6 (IL-6)
Interleukin 1 beta (IL-1 beta)
Brain-Buffer Insoluble beta Amyloid Peptide 40
Brain-Buffer Insoluble beta Amyloid Peptide 42
Electron Microscopy
Aggregated beta Amyloid Peptide
Cell Biology
Cell Viability
Nitric Oxide Release
ADME