Inhibitory effect of isoliquiritigenin isolated from Glycyrrhizae Radix on amyloid-β production in Swedish mutant amyloid precursor protein-transfected Neuro2a cells

Abstract

Alzheimer's disease (AD) is a form of dementia, and its pathological characteristics involve the accumulation of amyloid-β (Aβ) produced by the cleavage of amyloid precursor protein (APP). According to the amyloidogenic pathway, Aβ is generated by the initial action of the β-site APP cleaving enzyme (BACE1), which forms the Aβ-containing C-terminal fragment (β-CTF) and soluble APP-β (sAPPβ). Consequently, β-CTF is cleaved by γ-secretase to yield Aβ. Therefore, the investigation of inhibitors of Aβ generation could be a strategy for AD therapy. Isoliquiritigenin inhibited BACE1 (IC50, 51.5 µM; Ki, 51.83 µM) but not BACE1 expression in Swedish mutant APP-transfected Neuro2a cells. The levels of Aβ1–40 and Aβ1–42 in the cell culture media and intracellular Aβ1–42 were reduced by 10 µM isoliquiritigenin. These effects were attributable to β-CTF and sAPPβ reduction via inhibition of cellular BACE1 activity. The data presented that isoliquiritigenin could play a role as a potent BACE1 inhibitor.