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Protective effects of 6-(Methylsulfinyl)hexyl Isothiocyanate on Aβ1-42-induced cognitive deficit, oxidative stress, inflammation, and apoptosis in mice

Bibliographic

Year of Publication:
2018
Contact PI Name:
Fabiana Morroni
Contact PI Affiliation:
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
Co-Authors:
Giulia Sita, Agnese Graziosi, Eleonora Turrini, Carmela Fimognari, Andrea Tarozzi, Patrizia Hrelia
Primary Reference (PubMED ID):
Funding Source:
Ministero dell'Istruzione dell'Università e della Ricerca (MIUR)
Study Goal and Principal Findings:

Alzheimer’s disease (AD) is the most common form of dementia among older people. Although soluble amyloid species are recognized triggers of the disease, no therapeutic approach is able to stop it. 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in Wasabia japonica, which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties. The aim of the present study was to investigate the neuroprotective activity of 6-MSITC in a murine AD model, induced by intracerebroventricular injection of β-amyloid oligomers (Aβ1-42O). The treatment with 6-MSITC started 1 h after the surgery for the next 10 days. Behavioral analysis showed that 6-MSITC ameliorated Aβ1-42O-induced memory impairments. The decrease of glutathione levels and increase of reactive oxygen species in hippocampal tissues following Aβ1-42O injection were reduced by 6-MSITC. Moreover, activation of caspases, increase of inflammatory factors, and phosphorylation of ERK and GSK3 were inhibited by 6-MSITC. These results highlighted an interesting neuroprotective activity of 6-MSITC, which was able to restore a physiological oxidative status, interfere positively with Nrf2-pathway, decrease apoptosis and neuroinflammation and contribute to behavioral recovery. Taken together, these findings demonstrated that 6-MSITC could be a promising complement for AD therapy.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC)
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:
C57BL/6

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
Passive Avoidance Test
Motor Function
Path Length
Swimming Speed
Histopathology
Activated Astrocytes
Activated Microglia
Neuronal Loss
Biochemical
Caspase Activation
Caspase 3
Caspase 9
Extracellular Signal-Regulated Kinase 1/2 (ERK1/2)
phospho-Extracellular Signal-Regulated Kinase 1/2 (phospho-ERK1/2)
Glycogen Synthase Kinase 3 beta (GSK3 beta)
phospho-Glycogen Synthase Kinase 3 beta (phospho-GSK3 beta)
Glutathione (GSH)
Inducible Nitric Oxide Synthase (iNOS/NOS2) mRNA
Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activation
Reactive Oxygen Species (ROS)
Immunochemistry
Glial Fibrillary Acidic Protein (GFAP)
Ionized Calcium Binding Adaptor Molecule 1 (Iba1)
Microscopy
Neuronal Cell Number
Neuronal Loss
Neuronal Morphology