title: (-)-Epigallocatechin-3-gallate prevents lipopolysaccharide-induced elevation of beta-amyloid generation and memory deficiency.
abstract: Neuroinflammation has been known to play a role in the pathogenesis of AD. Our previous study showed that lipopolysaccharide (LPS) induced memory impairment through the accumulation of Abeta via the increase of beta- and gamma-secretase. In this study, we investigated the possible preventive effect of (-)-epigallocatechin-3-gallate (EGCG) on memory deficiency caused by LPS through the inhibition of Abeta(1-42) generation. Oral treatment with EGCG (1.5 and 3 mg/kg, for 3 weeks) into drinking water ameliorated LPS (1 microg/mouse, i.c.v.)-induced memory deficiency in a dose dependent manner. In addition, EGCG also dose-dependently inhibited LPS-induced elevation of Abeta level through attenuation of LPS-induced beta- and gamma-secretase activities and expression of its metabolic products; C99 and Abeta. Moreover, EGCG prevented LPS-induced neuronal cell death as well as the expression of inflammatory proteins, inducible nitric oxide synthetase and cyclooxygenase-2. This study therefore suggests that EGCG prevents LPS-mediated apoptotic cell death through the inhibition of the elevation of Abeta via the inhibition of beta- and gamma-secretases, and thus EGCG can be a useful agent against neuroinflammation-associated development or progression of AD.
authors.affiliation: College of Pharmacy, Chungbuk National University 12, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Young Kyoung
authors.initials: YK
authors.lastname: Lee
authors.forename: Dong Yeon
authors.initials: DY
authors.lastname: Yuk
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Lee
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Tae Youl
authors.initials: TY
authors.lastname: Ha
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Yeo Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C528900:glial fibrillary astrocytic protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D053829:Amyloid Precursor Protein Secretases