Skip to main content
U.S. flag

An official website of the United States government

6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer’s disease via CysLT1R-mediated inhibition of cathepsin B

Bibliographic

Year of Publication:
2016
Contact PI Name:
Jungkee Kwon
Contact PI Affiliation:
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
Co-Authors:
Ji-Young Na, Kibbeum Song, Ju-Woon Lee, Sokho Kim
Primary Reference (PubMED ID):
Funding Source:
Jeonbuk Research & Development Program
National Research Foundation of Korea (NRF)
Study Goal and Principal Findings:

Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, the effects of 6-shogaol on Alzheimer's disease (AD) have not yet been investigated. Here we aimed to determine whether 6-shogaol exerts neuroprotective effects against AD. Specifically, we investigated the effects of 6-shogaol on the cysteinyl leukotriene 1 receptor (CysLT1R), a major factor in AD pathogenesis. Moreover, we clarified the relationship between CysLT1R and cathepsin B, a cysteine protease. We used in vitro and in vivo models to determine whether 6-shogaol inhibits CysLT1R/cathepsin B in an amyloid-beta (Aβ; 1-42)-induced model of neurotoxicity. We first confirmed that CysLT1R and cathepsin B are upregulated by Aβ (1-42) and that CysLT1R activation induces cathepsin B. In contrast, we found that 6-shogaol-mediated inhibition of CysLT1R downregulates cathepsin B in both in vitro and in vivo models. Furthermore, we found that 6-shogaol-mediated inhibition of CysLT1R/cathepsin B reduces Aβ deposition in the brain and ameliorates behavioral deficits in APPSw/PS1-dE9 Tg mice. Our results indicate that 6-shogaol is a CysLT1R/cathepsin B inhibitor and is a novel potential therapeutic agent for the treatment of various neurodegenerative diseases, including AD.

Bibliographic Notes:
Sokho Kim and Jungkee Kwon (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea) are corresponding authors on this paper.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
6-Shogaol
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
C57BL/6J

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
Nesting Behavior
Step-Through Passive Avoidance Test
Biochemical
Cathepsin B
Cysteinyl Leukotriene 1 Receptor (CysLT1R)
Brain-beta Amyloid Peptide 42
Cell Biology
Cell Viability
Cytotoxicity