Skip to main content
U.S. flag

An official website of the United States government

Maysin and its flavonoid derivative from centipedegrass attenuates amyloid plaques by inducting humoral immune response with Th2 skewed cytokine response in the Tg (APPswe, PS1dE9) Alzheimer's mouse model

Bibliographic

Year of Publication:
2017
Contact PI Name:
Jae-Hyeon Cho
Contact PI Affiliation:
Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea
Co-Authors:
Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Hyoung-Woo Bai, Seung Sik Lee, SungBeom Lee, Byung Yeoup Chung
Primary Reference (PubMED ID):
Funding Source:
National Research Foundation of Korea (NRF)
Korean Ministry of Education, Science and Technology (MEST)
Study Goal and Principal Findings:

Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. Previous studies found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models. This study examined the preventative effects of EA-CG treatment on the Aβ burden in the Tg (Mo/Hu APPswe PS1dE9) AD mouse model. They investigated the EA-CG efficacy as novel anti-AD likely preventing amyloid plaques using immunofluorescence staining to visually analyze Aβ40/42 and fibril formation with Thioflavin-S or 6E10 which are the profile of immunoreactivity against epitope Aβ1±16 or neuritic plaque, the quantitation of humoral immune response against Aβ, and the inflammatory cytokine responses (Th1 and Th2) using ELISA and QRT-PCR. To minimize the toxicity of the extracted CG, they addressed the liver toxicity in response to the CG extract treatment in Tg mice using relevant markers, such as aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) measurements in serum. The EA-CG extract significantly reduced the Aβ burden, the concentration of soluble Aβ40/42 protein, and fibril formation in the hippocampus and cortex of the Tg mice treated with EA-CG (50 mg/kg BW/day) for 6 months compared with the Tg mice treated with a normal diet. Additionally, the profile of anti-inflammatory cytokines revealed that the levels of Th2 (interleukin-4 (IL-4) and interleukin-10 (IL-10)) cytokines are more significantly increased than Th1 (interferon-γ (IFN-γ), interleukin-2(IL-2)) in the sera. These results suggest that the EA-CG fraction induces IL-4/IL-10-dependent anti-inflammatory cytokines (Th2) rather than pro-inflammatory cytokines (Th1), which are driven by IL-2/IFN-γ. With regard to the immune response, EA-CG induced an immunoglobulin IgG and IgM response against the EA-CG treatment in the Tg mice. Furthermore, EA-CG significantly ameliorated the level of soluble Aβ42 and Aβ40. Similarly, the fibril formation was also decreased by EA-CG treatment in the hippocampus and cortex after quantitative analysis with Thioflavin-S staining in the Tg brain tissues. Taken together, these findings suggested that Maysin and its derivative flavonoid compounds in the EA-CG fraction might be beneficial therapeutic treatments or alternative preventative measures to adjuvant for boosting humoral and cellular include immune response and anti-inflammation which may lead to amyloid plaque accumulation in Alzheimer's patients' brains.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Natural Product
Therapeutic Agent:
Luteolin
Therapeutic Target:
Multi Target
Therapy Type:
Natural Product
Therapeutic Agent:
Isoorientin
Therapeutic Target:
Multi Target
Therapy Type:
Natural Product
Therapeutic Agent:
Rhamnosylisoorientin
Therapeutic Target:
Multi Target
Therapy Type:
Natural Product
Therapeutic Agent:
Derhamnosylmaysin
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
B6C3

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
Histopathology
Dense-core/Compact Plaques
beta Amyloid Deposits
Fibrillar beta Amyloid Deposits
beta Amyloid Load
Biochemical
Aspartate Aminotransferase (AST)
Alanine Aminotransferase (ALT)
Cytokines
Plasma-Interferon (IFN) gamma
Interleukin 4 (IL-4)
Interleukin 2 (IL-2)
Interleukin 10 (IL-10)
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Interferon (IFN) gamma mRNA
Tumor Necrosis Factor alpha (TNF alpha)
Interleukin 1 alpha (IL-1 alpha)
Interleukin 1 beta (IL-1 beta)
Immunochemistry
Brain-beta Amyloid Deposits
Immunology
Antibody Titers
Antibody Isotypes
T Cell Response
Toxicology
Toxicity-Liver