(−)-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 Aβ via the increase of β- and γ-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 Aβ1–42 generation. Oral treatment with EGCG (1.5 and 3 mg/kg, for 3 weeks) into drinking water ameliorated LPS (1 μg/mouse, i.c.v.)-induced memory deficiency in a dose dependent manner. In addition, EGCG also dose-dependently inhibited LPS-induced elevation of Aβ level through attenuation of LPS-induced β- and γ-secretase activities and expression of its metabolic products; C99 and Aβ. 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 Aβ via the inhibition of β- and γ-secretases, and thus EGCG can be a useful agent against neuroinflammation-associated development or progression of AD.