title: Epigallocatechin-3-gallate prevents systemic inflammation-induced memory deficiency and amyloidogenesis via its anti-neuroinflammatory properties.
abstract: Neuroinflammation has been known to play a critical role in the pathogenesis of Alzheimer's disease (AD) through amyloidogenesis. In a previous study, we found that systemic inflammation by intraperitoneal (ip) injection of lipopolysaccharide (LPS) induces neuroinflammation and triggers memory impairment. In this present study, we investigated the inhibitory effects of epigallocatechin-3-gallate (EGCG) on the systemic inflammation-induced neuroinflammation and amyloidogenesis as well as memory impairment. ICR mice were orally administered with EGCG (1.5 and 3 mg/kg) for 3 weeks, and then the mice were treated by ip injection of LPS (250 μg/kg) for 7 days. We found that treatment of LPS induced memory-deficiency-like behavior and that EGCG treatment prevented LPS-induced memory impairment and apoptotic neuronal cell death. EGCG also suppressed LPS-induced increase of the amyloid beta-peptide level and the expression of the amyloid precursor protein (APP), β-site APP cleaving enzyme 1 and its product C99. In addition, we found that EGCG prevented LPS-induced activation of astrocytes and elevation of cytokines including tumor necrosis factor-α, interleukin (IL)-1β, macrophage colony-stimulating factor, soluble intercellular adhesion molecule-1 and IL-16, and the increase of inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase-2, which are known factors responsible for not only activation of astrocytes but also amyloidogenesis. In the cultured astrocytes, EGCG also inhibited LPS-induced cytokine release and amyloidogenesis. Thus, this study shows that EGCG prevents memory impairment as well as amyloidogenesis via inhibition of neuroinflammatory-related cytokines released from astrocytes and suggests that EGCG might be a useful intervention for neuroinflammation-associated AD.
authors.affiliation: College of Pharmacy, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea.
authors.forename: Young-Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Choi
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008569:Memory Disorders / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002392:Catechin; C045651:epigallocatechin gallate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2