title: Diosmin reduces cerebral Aβ levels, tau hyperphosphorylation, neuroinflammation, and cognitive impairment in the 3xTg-AD mice.
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.
authors.affiliation: 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.
authors.forename: Darrell
authors.initials: D
authors.lastname: Sawmiller
authors.affiliation: Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: Ahsan
authors.initials: A
authors.lastname: Habib
authors.affiliation: 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.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: Donna
authors.initials: D
authors.lastname: Darlington
authors.affiliation: Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: Huayan
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.affiliation: Center for Aging & Brain Repair, Department of Neurosurgery & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Shytle
authors.affiliation: Center for Aging & Brain Repair, Department of Neurosurgery & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Smith
authors.affiliation: Neuroimmunology Laboratory, Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Giunta
authors.affiliation: Departments of Biomedical Sciences and Pathology, Saitama Medical Center and Saitama Medical University, Kawagoe, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mori
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004145:Diosmin / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D004145:Diosmin
keywords: Alzheimer's disease; Aβ; Diosmin; GSK-3; Neuroinflammation; Tau; γ-Secretase