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.

scholarly journals Volatile terpenoids as potential drug leads in Alzheimer’s disease

2017 ◽  
Vol 15 (1) ◽  
pp. 332-343 ◽  
Author(s):  
Karolina A. Wojtunik-Kulesza ◽  
Katarzyna Targowska-Duda ◽  
Katarzyna Klimek ◽  
Grażyna Ginalska ◽  
Krzysztof Jóźwiak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mtt Assay ◽  
Inhibitory Activity ◽  
Biological Activities ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
Docking Simulations ◽  
Ache Inhibitory Activity ◽  
Volatile Terpenoids

AbstractAlzheimer’s disease (AD) is by far the most prevalent of all known forms of dementia. Despite wide-spread research, the main causes of emergence and development of AD have not been fully recognized. Natural, low-molecular, lipophilic terpenoids constitute an interesting group of secondary plant metabolites, that exert biological activities of possible use in the prevention and treatment of AD. In order to identify secondary metabolites possessing both antioxidant activity and the potential to increase the level of acetylcholine, selected terpenoids have been screened for possible acetylcholinesterase inhibitory activity by use of two methods, namely Marston (chromatographic assay) and Ellman (spectrophotometric assay). In order to describe the interaction between terpenes and AChE active gorge, molecular docking simulations were performed. Additionally, all analyzed terpenes were also evaluated for their cytotoxic properties against two normal cell lines using MTT assay. The obtained results show that: carvone (6), pulegone (8) and γ-terpinene (7) possess desirable AChE inhibitory activity. MTT assay revealed low or lack of cytotoxicity of these metabolites. Thus, among the investigated terpenes, carvone (6), pulegone (8) and y-terpinene (7) can be recognized as compounds with most promising activities in the development of multi-target directed ligands.

[P3-245]: ANALYSIS OF THE HUMORAL RESPONSE IN ALZHEIMER's DISEASE USING THE HIGH-THROUGHPUT SCREENING COMBINATION OF T7 PHAGE LIBRARIES AND PROTEIN MICROARRAYS

2017 ◽  
Vol 13 (7S_Part_21) ◽  
pp. P1034-P1034
Author(s):  
Pablo San Segundo-Acosta ◽  
Ana Montero-Calle ◽  
Maria Garranzo-Asensio ◽  
Carmen Oeo-Santos ◽  
Juan Carlos López-Rodríguez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Throughput ◽  
High Throughput Screening ◽  
Humoral Response ◽  
Protein Microarrays ◽  
Phage Libraries ◽  
T7 Phage

Development of Phthalimide-Donepezil Hybrids as Potent Multitarget- Directed Ligands for the Treatment of Alzheimer’s Disease

2020 ◽  
Vol 17 (9) ◽  
pp. 1155-1163
Author(s):  
Lintao Yu ◽  
Jian Shi ◽  
Xinfeng Cheng ◽  
Keren Wang ◽  
Shuang Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inhibitory Activity ◽  
Biological Activities ◽  
Docking Study ◽  
Binding Mode ◽  
Mao B ◽  
Ic50 Value ◽  
Ache Inhibitory Activity

Background: Due to the complex etiology of AD, multi-target-directed ligands (MTDLs), combining two or more distinct pharmacological moieties, have been developed in both symptomatic and disease-modifying efficiencies and are considered as an effective way for the treatment of AD. Methods: To test their biological activities, including AChE/BChE inhibitory activity and MAOA/ MAO-B inhibitory activity. In addition, molecular modeling studies were performed to afford insight into the binding mode. Results: The results displayed that compound 4c showed the best AChE inhibitory activity with an IC50 value of 4.2 μM, which was supported by the kinetic study and docking study. Compound 4c was also a selective MAO-B inhibitor (IC50 = 8.2 μM). Moreover, compound 4c could cross the blood-brain barrier in vitro. Conclusion: Compound 4c deserved to further study as a potential multifunctional agent for the treatment of Alzheimer’s disease.

scholarly journals High Throughput Screening at the Membrane Interface Reveals New Inhibitors of Amyloid-β

2019 ◽  
Author(s):  
Sarah J. Cox ◽  
Brian Lam ◽  
Ajay Prasad ◽  
Hannah A. Marietta ◽  
Nicholas V. Stander ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Membrane ◽  
Small Molecules ◽  
High Throughput ◽  
High Throughput Screening ◽  
Amyloid Β ◽  
Amyloid Aggregation ◽  
Membrane Interface

Amyloid-β aggregation at the cell-membrane of neruonal cells is implicated as a source of toxicity for Alzheimer’s disease. Small molecules have been studied for their ability to supress amyloid aggregation and toxicity, but the presence of membranes negate their activity. Here, we have identified 5 small molecules that are active at the membrane interface.

scholarly journals A Platform for Screening Potential Anticholinesterase Fractions and Components Obtained fromAnemarrhena asphodeloidesBge for Treating Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Sun ◽  
Ying Peng ◽  
Lin-Guang Li ◽  
Li-Wei Zheng ◽  
Dong-Ju Lin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inhibitory Activity ◽  
Memory Loss ◽  
Symptomatic Treatment ◽  
Ache Inhibitory Activity ◽  
Screening Platform ◽  
Ellman’S Method ◽  
Anemarrhena Asphodeloides ◽  
Ethanol Fraction

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. Cholinesterase inhibitors are widely used for the symptomatic treatment of Alzheimer’s disease to enhance central cholinergic transmission. In this study, a bioactivity-oriented screening platform based on a modified Ellman’s method and HPLC-QTOF MS technique was developed to rapidly screen active agents ofAnemarrhena asphodeloidesBge. The 60% ethanol fraction from an ethyl acetate extract exhibited the most potential anticholinesterase activity. Fifteen steroid saponins were identified by the mass spectrum, standards and literature reports. Twenty-five compounds were isolated from the active fraction. The results showed that compounds with the C6–C3–C6skeleton probably had both AChE and BuChE inhibitory activities. Xanthone and benzene derivatives exhibited no or little activity. Lignans showed weak BuChE inhibitory activity. The steroidal saponins demonstrated moderate or weak AChE inhibitory activity.

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