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

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Chan Hum Park ◽  
Min Jo Kim ◽  
Hyun Ah Jung ◽  
Jae Sue Choi ◽  
Jin Pyeong Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Water Extract ◽  
Kinase Assay ◽  
Salvianolic Acid ◽  
Salviae Miltiorrhizae ◽  
Crude Drug ◽  
Magnesium Lithospermate B ◽  
Salviae Miltiorrhizae Radix ◽  
Gsk 3Β

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.

An integrated strategy for rapid screening of multi-target lead compounds for the treatment of Alzheimer's disease from traditional Chinese medicines by UHPLC combined with high-throughput screening: A case study on Salviae Miltiorrhizae Radix et Rhizoma

2021 ◽  
Vol 17 ◽  
Author(s):  
Minmin Zhang ◽  
Siduo Zhou ◽  
Wei Liu ◽  
Huijiao Yan ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Throughput ◽  
Inhibitory Activity ◽  
High Throughput Screening ◽  
Hplc Analysis ◽  
Salviae Miltiorrhizae ◽  
Salviae Miltiorrhizae Radix ◽  
Ache Inhibitory Activity

Background: Salviae Miltiorrhizae Radix et Rhizoma (Red Sage root) is widely used in traditional Chinese medicine (TCM) for the treatment of Alzheimer’s disease (AD) with demonstrated curative effects, based on the concept of "one drug with multiple therapeutic targets," which appears to be a good strategy for AD treatment. Objective: This study aimed to develop of high-throughput screening (HTS) method for multi-therapeutic target components found in complex TCMs, which are active against AD, using Red Sage root as the case study. Method: Acetylcholinesterase (AChE) inhibitors (AChEIs) from Red Sage root extracts were pre-screened by ultrafiltration-HPLC (UF-HPLC) analysis, in which AChE was added to the extract and then ultrafiltered to remove non-binding compounds. Potential AChEIs were identified by HPLC analysis of compounds bound to AChE. A microplate-based HTS was then used to quantify the AChE inhibitory activity and antioxidant activity of the pre-screened compounds. Results: Pre-screening found ten potential inhibitors, which were identified by ESI-TOF/MS; six of these were purified by semi-preparative HPLC: Oleoyl neocryptotanshinone (1), Dihydrotanshinone Ⅰ (2), Cryptotanshinone (3), Tanshinone Ⅰ (4), Tanshinone ⅡA (5) and Miltirone (6). All six compounds had good AChE inhibitory activity and weak DPPH scavenging capacity. Conclusion: This study provides a platform and technology support for the rapid discovery of multi-target components, potentially active against AD, from complex TCMs and with strong potential for adaptation to the discovery of treatments for other diseases.

Polycyclic maleimide-based derivatives as first dual modulators of neuronal calcium channels and GSK-3β for Alzheimer's disease treatment

2019 ◽  
Vol 163 ◽  
pp. 394-402 ◽  
Author(s):  
Alessandra Bisi ◽  
Raquel L. Arribas ◽  
Matteo Micucci ◽  
Roberta Budriesi ◽  
Alessandra Feoli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Calcium Channels ◽  
Disease Treatment ◽  
Gsk 3Β ◽  
Neuronal Calcium Channels

scholarly journals Contribution of prostaglandins to the renal responses to magnesium lithospermate B isolated from Salviae Miltiorrhizae Radix.

1989 ◽  
Vol 37 (6) ◽  
pp. 1568-1571 ◽  
Author(s):  
Takako YOKOZAWA ◽  
Hae Young CHUNG ◽  
Tae Woong LEE ◽  
Hikokichi OURA ◽  
Takashi TANAKA ◽  
...  
Keyword(s):  
Salviae Miltiorrhizae ◽  
Magnesium Lithospermate B ◽  
Salviae Miltiorrhizae Radix ◽  
Renal Responses

Virtual Screening in Chinese Herbs with Multi-Target Effect on Alzheimer's Disease

2013 ◽  
Vol 765-767 ◽  
pp. 256-260
Author(s):  
Yan Ling Zhang ◽  
Yuan Ming Wang ◽  
Yan Jiang Qiao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Virtual Screening ◽  
Glycogen Synthase ◽  
Chinese Herbs ◽  
Multiple Targets ◽  
Active Compounds ◽  
Ache Inhibitors ◽  
Gsk 3Β ◽  
Pharmacophore Models

Multiple targets which closely related to Alzheimer's disease (AD) pathogenesis were selected for pharmacophore models generation and virtual screening in Chinese herbs. The targets comprised Acetylcholinesterase (AchE), muscarinic receptor 1 (M1), γ-secretase and glycogen synthase kinase 3β (GSK-3β). The pharmacophore models, which of AchE inhibitors, M1 agonists, γ-secretase inhibitors and GSK-3β inhibitors, were constructed by distance comparison method. Four testing databases for the evaluation of pharmacophore models were constructed with the active compounds with clearly marked activity on each target. The metric CAI (Comprehensive Appraisal Index) was then used to evaluate and obtain the best pharmacophore models of each target, which were then applied to screen the Traditional Chinese Medicine Database for potential active compounds in Chinese herbs. Four common used herbs were obtained, which contain the active compounds and can act on multiple targets, and were expected to have multiple activity of anti-AD disease.

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