title: Iso-α-acids, Bitter Components of Beer, Prevent Inflammation and Cognitive Decline Induced in a Mouse Model of Alzheimer's Disease.
abstract: Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor γ. In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia (p< 0.05) and in microglial phagocytosis in the brain. In Alzheimer's model 5xFAD mice, oral administration of iso-α-acids resulted in a 21% reduction in amyloid β in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1β and chemokines including macrophage inflammatory protein-1α in the cerebral cortex (p< 0.05) and a significant improvement in a novel object recognition test (p< 0.05), as compared with control-fed 5xFAD mice. The differences in iso-α-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid β deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-α-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-α-acids contained in beer may be useful for the prevention of dementia.
authors.affiliation: From the Research Laboratories for Health Science & Food Technologies and Yasuhisa_Ano@kirin.co.jp.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ano
authors.affiliation: the Graduate School of Agricultural and Life Sciences, the University of Tokyo, Tokyo 113-8657, Japan, and.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Dohata
authors.affiliation: the Central Laboratories for Key Technologies, Kirin Company Ltd., Kanagawa 236-0004, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: the Central Laboratories for Key Technologies, Kirin Company Ltd., Kanagawa 236-0004, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Hoshi
authors.affiliation: the Graduate School of Agricultural and Life Sciences, the University of Tokyo, Tokyo 113-8657, Japan, and.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Uchida
authors.affiliation: the Department of Neurobiology, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
authors.affiliation: the Graduate School of Agricultural and Life Sciences, the University of Tokyo, Tokyo 113-8657, Japan, and.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D000143:Acids / Q000737:chemistry*; D000284:Administration, Oral; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001515:Beer; D001812:Blood-Brain Barrier; D039481:CD11b Antigen / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D060825:Cognitive Dysfunction / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000517:prevention & control*; D037181:Lectins, C-Type / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D010587:Phagocytosis; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D000143:Acids; D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface
keywords: Alzheimer disease; inflammation; microglia; neuroinflammation; phagocytosis