Chinese Prescription Kangen-karyu as Potential Anti-Alzheimer’s Disease Therapeutic: Analyses of BACE1 and GSK-3b Inhibitory Activities

Abstract

Inhibition of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) or glycogen synthase kinase-3β (GSK-3β) is estimated to be the central therapeutic approach for Alzheimer’s disease (AD). In this study, water extract of Kangenkaryu, its crude drug and chemical composition used in oriental medicine were evaluated regarding their BACE1 and GSK-3β inhibitory activities.Fluorescence resonance energy transfer was used to characterize the BACE1 inhibitory effect of Kangen-karyu, its crude drug and chemical composition.GSK-3β activity was determined using the Kinase-Glo Luminescent Kinase Assay Platform. The water extract of Kangen-karyu inhibited BACE1 and GSK-3β in concentration-dependent manners when compared with reference drugs, quercetin and luteolin. Among six components of Kangen-karyu, the water extracts of Salviae Miltiorrhizae Radix or Cyperi Rhizoma exhibited significant inhibitory effects on BACE1 and GSK-3β. Among the constituents of Salviae Miltiorrhizae Radix extract, salvianolic acid C, salvianolic acid A, rosmarinic acid, and magnesium lithospermate B significantly inhibited BACE1. In addition, they inhibited GSK-3β with an IC50 value range of 6.97 to 135.35 μM. From these results, one of the effectiveness and its mechanisms of action of Kangen-karyu against AD may be the inhibition of BACE1 and GSK-3β, and one of the active ingredients of Kangen-karyu is Salviae Miltiorrhizae Radix and its constituents.