(-)-Epigallocatechin-3-gallate prevents lipopolysaccharide-induced elevation of beta-amyloid generation and memory deficiency.
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.
Lee
Young Kyoung
YK
College of Pharmacy, Chungbuk National University 12, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
Yuk
Dong Yeon
DY
Lee
Jae Woong
JW
Lee
Sun Young
SY
Ha
Tae Youl
TY
Oh
Ki Wan
KW
Yun
Yeo Pyo
YP
Hong
Jin Tae
JT
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
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