Phlorotannin-rich Ecklonia cava reduces the production of beta-amyloid by modulating alpha- and gamma-secretase expression and activity.

Beta-amyloid (Aβ) is a major pathogenic peptide in Alzheimer's disease (AD) and is generated by the processing of amyloid precursor protein (APP). We have previously reported that the brown algae Ecklonia cava, which has anti-oxidant and anti-inflammatory functions, decreased Aβ production and further aggregation in HEK293 cells expressing the APP Swedish mutation. Here, we show the reduction mechanism of Aβ production using the butanol extract of Ecklonia cava through the examination of expression and activity of alpha-, beta-, and gamma-secretase. Treatment with the extract resulted in the activation of alpha-secretase with a contrasting decrease in its mRNA and protein expression. This activation was consistent with the translocation of the extract into the plasma membrane of the secretase. Gamma-secretase activity was lowered by E. cava, and this effect may be due to the decreased expression of PSEN1 mRNA and protein. In addition, the basal nuclear location of PSEN1, which may affect chromosome missegregation in neurodegenerative disease, was reduced by the extract, despite the significance of this finding remains unclear. Taken together, these results led us to conclude that E. cava regulated the expression and activity of gamma-secretase and alpha-secretase, leading to a reduction in Aβ production by the stable cells. Our data indicate that E. cava is a novel natural-product candidate for AD treatment, although further in vivo studies are needed.