scholarly journals Comparative Neuroprotective Effects of Dietary Curcumin and Solid Lipid Curcumin Particles in Cultured Mouse Neuroblastoma Cells after Exposure to Aβ42

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Panchanan Maiti ◽  
Gary L. Dunbar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Survival ◽  
Apoptotic Cell ◽  
Neuroblastoma Cells ◽  
Neuroprotective Effects ◽  
Solid Lipid ◽  
Mouse Neuroblastoma ◽  
Phosphorylated Akt

Aggregation of amyloid beta protein (Aβ) and phosphorylated tau (p-Tau) plays critical roles in pathogenesis of Alzheimer’s disease (AD). As an antiamyloid natural polyphenol, curcumin (Cur) has a potential role in prevention of neurodegeneration in AD. However, due to limited absorption of the dietary Cur, the solid lipid Cur particles (SLCP) have been suggested as being more effective for AD therapy. In the present study, we compared the role of dietary Cur and SLCP on oxidative stress, neuronal death, p-Tau level, and certain cell survival markers in vitro, after exposure to Aβ42. Mouse neuroblastoma cells were exposed to Aβ42 for 24 h and incubated with or without dietary Cur and/or SLCP. Reactive oxygen species (ROS), apoptotic cell death, p-Tau, and tau kinase (including GSK-3β and cell survival markers, such as total Akt, phosphorylated Akt, and PSD95 levels) were investigated. SLCP showed greater permeability than dietary Cur in vitro, decreased ROS production, and prevented apoptotic death. In addition, SLCP also inhibited p-Tau formation and significantly decreased GSK-3β levels. Further, the cell survival markers, such as total Akt, p-Akt, and PSD95 levels, were more effectively maintained by SLCP than dietary Cur in Aβ42 exposed cells. Therefore, SLCP may provide greater neuroprotection than dietary Cur in Alzheimer’s disease.

scholarly journals Synergistic Action of Flavonoids, Baicalein, and Daidzein in Estrogenic and Neuroprotective Effects: A Development of Potential Health Products and Therapeutic Drugs against Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Roy C. Y. Choi ◽  
Judy T. T. Zhu ◽  
Amanda W. Y. Yung ◽  
Pinky S. C. Lee ◽  
Sherry L. Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcriptional Activation ◽  
Estrogenic Activity ◽  
Neuroprotective Effects ◽  
Potential Health ◽  
Amyloid A ◽  
Therapeutic Drugs ◽  
Health Products

Despite the classical hormonal effect, estrogen has been reported to mediate neuroprotection in the brain, which leads to the searching of estrogen-like substances for treating neurodegenerative diseases. Flavonoids, a group of natural compounds, are well known to possess estrogenic effects and used to substitute estrogen, that is, phytoestrogen. Flavonoid serves as one of the potential targets for the development of natural supplements and therapeutic drugs against different diseases. The neuroprotection activity of flavonoids was chosen for a possible development of anti-Alzheimer's drugs or food supplements. The estrogenic activity of two flavonoids, baicalein and daidzein, were demonstrated by their strong abilities in stimulating estrogen receptor phosphorylation and transcriptional activation of estrogen responsive element in MCF-7 breast cells. The neuroprotection effects of flavonoids againstβ-amyloid (Aβ) were revealed by their inhibition effects onin vitroAβaggregation and Aβ-induced cytotoxicity in PC12 neuronal cells. More importantly, the estrogenic and neuroprotective activities of individual flavonoid could be further enhanced by the cotreatment in the cultures. Taken together, this synergistic effect of baicalein and daidzein might serve as a method to improve the therapeutic efficacy of different flavonoids against Aβ, which might be crucial in developing those flavonoidsin treating Alzheimer's disease in the future.

scholarly journals Network Pharmacology-Based Study of the Underlying Mechanisms of Huangqi Sijunzi Decoction for Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wei Zhang ◽  
Mingti Lv ◽  
Yating Shi ◽  
Yonghui Mu ◽  
Zhaoyang Yao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroprotective Effect ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Network Pharmacology ◽  
Neuroprotective Effects ◽  
Target Network ◽  
Compound Target

Background. Huangqi Sijunzi decoction (HQSJZD) is a commonly used conventional Chinese herbal medicine prescription for invigorating Qi, tonifying Yang, and removing dampness. Modern pharmacology and clinical applications of HQSJZD have shown that it has a certain curative effect on Alzheimer’s disease (AD). Methods. The active components and targets of HQSJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database. The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of HQSJZD were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HQSJZD were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE. Results. Compound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc. There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of HQSJZD, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells. Conclusion. HQSJZD was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in HQSJZD may regulate multiple signalling pathways through AChE, which might play a therapeutic role in AD.

Neuroprotective effects of bergenin in Alzheimer’s disease: Investigation through molecular docking, in vitro and in vivo studies

2019 ◽  
Vol 356 ◽  
pp. 18-40 ◽  
Author(s):  
Priyal Barai ◽  
Nisith Raval ◽  
Sanjeev Acharya ◽  
Ankit Borisa ◽  
Hardik Bhatt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
In Vivo Studies ◽  
Neuroprotective Effects

scholarly journals Design, Synthesis, and In Vitro Evaluation of Hydroxybenzimidazole-Donepezil Analogues as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 985 ◽  
Author(s):  
Sílvia Chaves ◽  
Simonetta Resta ◽  
Federica Rinaldo ◽  
Marina Costa ◽  
Romane Josselin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroblastoma Cells ◽  
Biological Properties ◽  
Design Synthesis ◽  
Aβ Aggregation ◽  
Structural Isomerization ◽  
Good Potential ◽  
Nitro Derivatives

A series of multi-target-directed ligands (MTDLs), obtained by attachment of a hydroxyphenylbenzimidazole (BIM) unit to donepezil (DNP) active mimetic moiety (benzyl-piperidine/-piperazine) was designed, synthesized, and evaluated as potential anti-Alzheimer’s disease (AD) drugs in terms of biological activity (inhibition of acetylcholinesterase (AChE) and β–amyloid (Aβ) aggregation), metal chelation, and neuroprotection capacity. Among the DNP-BIM hybrids studied herein, the structural isomerization did not significantly improve the biological properties, while some substitutions, namely fluorine atom in each moiety or the methoxy group in the benzyl ring, evidenced higher cholinergic AChE activity. All the compounds are able to chelate Cu and Zn metal ions through their bidentate BIM moieties, but compound 5, containing a three-dentate chelating unit, is the strongest Cu(II) chelator. Concerning the viability on neuroblastoma cells, compounds 9 and 10 displayed the highest reduction of Aβ-induced cell toxicity. In silico calculations of some pharmacokinetic descriptors indicate that all the compounds but the nitro derivatives have good potential oral-bioavailability. Overall, it can be concluded that most of the studied DNP-BIM conjugates showed quite good anti-AD properties, therefore deserving to be considered in further studies with the aim of understanding and treating AD.

scholarly journals Multitarget Therapeutic Strategies for Alzheimer’s Disease: Review on Emerging Target Combinations

2020 ◽  
Vol 2020 ◽  
pp. 1-27 ◽  
Author(s):  
Samuele Maramai ◽  
Mohamed Benchekroun ◽  
Moustafa T. Gabr ◽  
Samir Yahiaoui
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Event ◽  
Neuroprotective Effects ◽  
New Agents ◽  
Major Health ◽  
New Treatment ◽  
Neuronal Functions

Neurodegenerative diseases represent nowadays one of the major health problems. Despite the efforts made to unveil the mechanism leading to neurodegeneration, it is still not entirely clear what triggers this phenomenon and what allows its progression. Nevertheless, it is accepted that neurodegeneration is a consequence of several detrimental processes, such as protein aggregation, oxidative stress, and neuroinflammation, finally resulting in the loss of neuronal functions. Starting from these evidences, there has been a wide search for novel agents able to address more than a single event at the same time, the so-called multitarget-directed ligands (MTDLs). These compounds originated from the combination of different pharmacophoric elements which endowed them with the ability to interfere with different enzymatic and/or receptor systems, or to exert neuroprotective effects by modulating proteins and metal homeostasis. MTDLs have been the focus of the latest strategies to discover a new treatment for Alzheimer’s disease (AD), which is considered the most common form of dementia characterized by neurodegeneration and cognitive dysfunctions. This review is aimed at collecting the latest and most interesting target combinations for the treatment of AD, with a detailed discussion on new agents with favorable in vitro properties and on optimized structures that have already been assessed in vivo in animal models of dementia.

scholarly journals Design and synthesis of multi-target directed 1,2,3-triazole-dimethylaminoacryloyl-chromenone derivatives with potential use in Alzheimer's disease

BMC Chemistry ◽  
2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Hajar Karimi Askarani ◽  
Aida Iraji ◽  
Arezoo Rastegari ◽  
Syed Nasir Abbas Bukhari ◽  
Omidreza Firuzi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Activities ◽  
Neuroprotective Effects ◽  
Design And Synthesis ◽  
Catalytic Active Site ◽  
Aβ Aggregation ◽  
Multifunctional Agents ◽  
Potential Use

Abstract To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a new series of 1,2,3-triazole-chromenone derivatives were designed and synthesized based on the multi target-directed ligands approach. The in vitro biological activities included acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition as well as anti-Aβ aggregation, neuroprotective effects, and metal-chelating properties. The results indicated a highly selective BuChE inhibitory activity with an IC50 value of 21.71 μM for compound 10h as the most potent compound. Besides, compound 10h could inhibit self-induced Aβ1–42 aggregation and AChE-induced Aβ aggregation with 32.6% and 29.4% inhibition values, respectively. The Lineweaver–Burk plot and molecular modeling study showed that compound 10h targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of BuChE. It should be noted that compound 10h was able to chelate biometals. Thus, the designed scaffold could be considered as multifunctional agents in AD drug discovery developments.

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