Anti-amyloidogenic effects of ID1201, the ethanolic extract of the fruits of Melia toosendan, through activation of the phosphatidylinositol 3-kinase/Akt pathway

• The ethanolic extract of Meliae Fructus (ID1201) showed anti-amyloidogenic effects in vitro.
• The anti-amyloidogenic effects were shown by the activation of PI3K/Akt pathway.
• ID1201 reduced Aβ40 and Aβ42 levels in vitro.
• ID1201 reduced Aβ40, Aβ42, and amyloid plaques in the 5 × FAD mice.

Amyloid beta (Aβ) peptides, which are generated from amyloid precursor protein (APP), are thought to play a major role in the pathogenesis of Alzheimer's disease (AD). This study investigated the anti-amyloidogenic effects of the ethanolic extract of Meliae Fructus (ID1201) using human embryonic kidney 293 cells with stably expressed human wild-type or Swedish mutant APP695 and β-secretase 1. ID1201 treatment enhanced the non-amyloidogenic metabolism of APP; increases in soluble APPα levels and decreases in soluble APPβ and Aβ levels resulted from the α-secretase activation through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In addition, ID1201-treated 5 × familial AD (FAD) mice with 5 mutations in APP and presenilin 1 showed reduced levels of Aβ and amyloid plaques in the brain relative to those of 5 × FAD mice with vehicle treatments. These results indicate that ID1201 possesses anti-amyloidogenic effects via the activation of the PI3K/Akt pathway, suggesting that it is a potential therapeutic agent for AD.