Format

Send to

Choose Destination
J Neuroimmunol. 2016 Oct 15;299:98-106. doi: 10.1016/j.jneuroim.2016.08.018. Epub 2016 Sep 1.

Diosmin reduces cerebral Aβ levels, tau hyperphosphorylation, neuroinflammation, and cognitive impairment in the 3xTg-AD mice.

Author information

1
Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States; James A. Haley Veteran's Administration Hospital, Tampa, FL, United States. Electronic address: dsawmill@health.usf.edu.
2
Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
3
Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States; Center for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
4
Center for Aging & Brain Repair, Department of Neurosurgery & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
5
Neuroimmunology Laboratory, Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
6
Departments of Biomedical Sciences and Pathology, Saitama Medical Center and Saitama Medical University, Kawagoe, Saitama, Japan.
7
Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States; James A. Haley Veteran's Administration Hospital, Tampa, FL, United States. Electronic address: jtan@health.usf.edu.

Abstract

Naturally-occurring bioactive flavonoids such as diosmin significantly reduces amyloid beta (Aβ) associated pathology in Alzheimer's disease (AD) mouse models. In the present study, oral administration of diosmin reduced cerebral Aβ oligomer levels, tau-hyperphosphorylation and cognitive impairment in the 3xTg-AD mouse model through glycogen synthase kinase-3 (GSK-3) and transient receptor potential canonical 6-related mechanisms. Diosmetin, one major bioactive metabolite of diosmin, increased inhibitory GSK-3β phosphorylation, while selectively reducing γ-secretase activity, Aβ generation, tau hyperphosphorylation and pro-inflammatory activation of microglia in vitro, without altering Notch processing. Therefore, both diosmin and diosmetin could be considered as potential candidates for novel anti-AD therapy.

KEYWORDS:

Alzheimer's disease; Aβ; Diosmin; GSK-3; Neuroinflammation; Tau; γ-Secretase

PMID:
27725131
PMCID:
PMC5074695
DOI:
10.1016/j.jneuroim.2016.08.018
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center