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

Chan Hum Park (Institute of New Frontier Research Team, Hallym Clinical and Translational Science Institute, Hallym University, Chuncheon, 24252, Republic of Korea)
Min Jo Kim (Department of Medicinal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, 369-873, Republic of Korea)
Hyun Ah Jung (Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea)
Jae Sue Choi (Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea)
Jin Pyeong Jeon (Institute of New Frontier Stroke Research Team, College of Medicine, Hallym University, Chuncheon, 24252, Republic of Korea;Department of Neurosurgery, College of Medicine, Hallym University, Chuncheon, 24252, Republic of Korea)
Takako Yokozawa (Graduate School of Science and Engineering for Research, University of Toyama, Toyama, 930-8555, Japan)

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.


Keywords


Alzheimer’s disease;β-Site amyloid precursor protein-cleaving enzyme 1;Glycogen synthase kinase-3β;Kangen-karyu;Salviae Miltiorrhizae Radix;Salvianolic acid C;Salvianolic acid B

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DOI: https://doi.org/10.30564/jim.v10i2.3441

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