scholarly journals Therapeutic Potential of Curcumin on the Cognitive Decline in Alzheimer’s Disease: A Study Integrated Meta-Analysis, Network Pharmacology, and Molecular Docking

2021 ◽  
Author(s):  
Zheyu Zhang ◽  
Hongli Li ◽  
Shan Hui ◽  
Min Yi ◽  
Xin Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Cognitive Deficits ◽  
Therapeutic Potential ◽  
Meta Analysis ◽  
Scientific Basis ◽  
Network Pharmacology ◽  
Integrated Network ◽  
Positive Effects

Abstract Background: Curcumin, a polyphenol derived from the herb turmeric, has emerged as a promising potential therapy in the management of Alzheimer’s disease (AD). However, the efficacy and potential therapeutic mechanisms remains largely unknown. Objective: To systematically meta-analysis the effect and to investigate the potential pharmacological mechanisms of curcumin on cognitive deficits in AD. Methods: A systematic collection of curcumin studies was performed from MEDLINE’s database, PubMed, Web of Science, and Google Scholar until October 31th, 2020. Following quality assessment of study eligibility, stratified meta-analysis and meta-regression analyses were undertaken to recognize and control the heterogeneity in meta-analysis. An integrated network pharmacology and molecular docking approach were applied to decipher the potential pharmacological mechanisms of curcumin on AD. Results: A meta-analysis of 29 publications showed that curcumin exerts significantly positive effects on cognitive performance. For acquisition, the global estimated effect of curcumin was -2.027 (95% CI: -2.435 to -1.619, p<0.001); For retention, the global estimated effect of curcumin was 1.606 (95% CI: 1.101 to 2.111, p<0.001). Stratified meta-analysis demonstrated that an increased effect size depended on various study characteristics. Network pharmacology analysis identified 63 genes targets, and STAT3, CHEK1, AKT1, EGFR, MMP9, hsp90AA1, and EP300 were core target proteins. Molecular docking showed that curcumin can closely bind with these seven targets. Besides, 69 potential pathways of curcumin were identified, like nitrogen metabolism.Conclusions: Our findings suggested that curcumin may reduce cognitive deficits in AD through multi-target and multi-pathway mechanism, providing a scientific basis for further experimental and clinical application.

scholarly journals Intravenous Immunoglobulin for Patients With Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 34 (5) ◽  
pp. 281-289 ◽  
Author(s):  
Apostolos Manolopoulos ◽  
Panagiotis Andreadis ◽  
Konstantinos Malandris ◽  
Ioannis Avgerinos ◽  
Thomas Karagiannis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intravenous Immunoglobulin ◽  
Therapeutic Potential ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Disease Assessment ◽  
Controlled Trials ◽  
Cognitive Subscale ◽  
Dosing Regimens

Aim:To assess the efficacy and safety of intravenous immunoglobulin (IVIg) for patients with Alzheimer’s disease (AD).Materials and Methods:We searched electronic databases and other sources for randomized controlled trials comparing IVIg with placebo or other treatment for adults with AD. Primary outcome was change from baseline in Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog).Results:Five placebo-controlled trials were included in the meta-analysis. Compared to placebo, IVIg 0.2 and 0.4 g/kg once every two weeks did not change ADAS-Cog score (weighted mean difference: 0.37, 95% confidence interval: −1.46 to 2.20 and 0.77, −1.34 to 2.88, respectively). Furthermore, except for an increase in the incidence of rash, IVIg did not affect the incidence of other adverse events.Conclusion:IVIg, albeit safe, is inefficacious for treatment of patients with AD. Future trials targeting earlier stages of disease or applying different dosing regimens may be warranted to clarify its therapeutic potential.

scholarly journals Study on the Mechanism of Acori Graminei Rhizoma in the Treatment of Alzheimer’s Disease Based on Network Pharmacology and Molecular Docking

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yi Kuan Du ◽  
Yue Xiao ◽  
Shao Min Zhong ◽  
Yi Xing Huang ◽  
Qian Wen Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
The Elderly ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Active Components

Alzheimer’s disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer’s disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of “drug-active ingredient-ingredient target.” A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer’s disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer’s signal pathway, thus reducing the production of Aβ, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.

scholarly journals Exploring the Mechanisms Underlying the Therapeutic Effect of Xixin Decoction on Alzheimer's Disease Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Zhuo Zhang ◽  
Jiang-lin Xu ◽  
Ming-qing Wei ◽  
Ting Li ◽  
Jing Shi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Therapeutic Effect ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Active Compounds

Abstract Background and objective: Alzheimer’s disease (AD) has been a worldwide problem, not only the treatment but also the prevention. As a commonly used Chinese Herbal Formula, Xixin Decoction (XXD) has significant therapeutic effect on AD but without clear mechanism. This study was aimed to predict the main active compounds and targets of XXD in the treatment of AD and to explore the potential mechanism by using network pharmacology and molecular docking. Methods: The compounds of XXD were searched in the TCMSP and the TCMID database, and the active compounds were screened based on the ADME model and SwissADME platform. SwissTargetPrediction platform was used to search for the primary candidate targets of XXD. The common targets related to AD obtained by two databases (GeneCards and DisGeNET) were determined as candidate proteins involved in AD. To acquire the related targets of XXD in the treatment of AD, the target proteins related to AD were intersected with the predicted targets of XXD. Then these overlapping targets were imported into the STRING database to build PPI network including hub targets; Cytoscape 3.7.2 software was used to construct the topology analysis for the herb-compound-target network diagram while one of it’s plug-in called CytoNCA was used to calculate degree value to screen the main active compounds of XXD. GO and KEGG pathway enrichment analyses were conducted to explore the core mechanism of action and biological pathways associated with the decoction via Metascape platform. We used AutoDock Vina and PyMOL 2.4.0 softwares for molecular docking of hub targets and main compounds.Results: We determined 114 active compounds which meet the conditions of ADME screening, 973 drug targets, and 973 disease targets. However, intersection analysis screened out 208 shared targets. PPI network identified 9 hub targets, including TP53, PIK3CA, MAPK1, MAPK3, STAT3, AKT1, etc. The 10 main active compounds play a major role in treatment of AD by XXD. Hub targets were found to be enriched in 10 KEGG pathways, involving the Pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, Alzheimer's disease, Neuroactive ligand-receptor interaction, Dopaminergic synapse, Serotonergic synapse and MAPK signaling pathway. The docking results indicated that the 8 hub targets exhibit good binding activity with the 9 main active compounds of XXD.Conclusions: We found the advantages of multi-compounds-multi-targets-multi-pathways regulation to reveal the mechanism of XXD for treating AD based on network pharmacology and molecular docking. Our study provided a theorical basis for further clinical application and experimental research of XXD for anti-AD in the future.

scholarly journals The Network Pharmacology Study And Molecular Docking To Investigate The Potential Mechanism of Acoritataninowii Rhizoma Against Alzheimer's Disease

2021 ◽  
Author(s):  
Jiali Pang ◽  
Jiali Pang ◽  
Zhi-Kun Qiu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Fluid Shear Stress ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Epstein Barr Virus Infection ◽  
Overlapping Genes ◽  
Potential Mechanism ◽  
Bioactive Ingredients

Abstract Background and objective: Alzheimer's Disease (AD) is considered as a progressively developing neurodegenerative disease with an insidious onset that induces increased cost of social burden and decreased quality of life. Acoritataninowii Rhizoma produced the effects of resuscitating and eliminating phlegm, dispelling dampness and appetizing, refreshing mind and nourishing the mind, and exerted the activities of anti-dementia and improving learning and memory. while little was relevant to its anti-AD mechanism. The present study explored the potential mechanism of Acoritataninowii Rhizoma defend AD by network pharmacology and molecular docking.Methods: The bioactive ingredients of Acoritataninowii Rhizoma were screened by absorption, distribution, metabolism as well as excretion evaluation and obtained from databases retrieval. Genes associated with AD or ingredients were searching by databases, and the overlapping genes between AD and ingredients were analyzed by the Venn diagram. Moreover, the network of Acoritataninowii Rhizoma-ingredients-targets-AD was visualized by cytoscape software. Furthermore, protein-protein interaction, gene ontology, pathway enrichment and molecular docking were conducted to evaluate potential factors of Acoritataninowii Rhizoma against AD.Results: 4 potential compounds were considered as bioactive ingredients after screening ADME. 81 ingredients-related genes and 6765 AD-related genes were screened by databases with 61 overlapping genes. The bioactive ingredients derived from Acoritataninowii Rhizoma (e.g Cycloartenol, (1R,3aS,4R,6aS)-1,4-bis(3,4-dimethoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro[4,3-c]furan, 8-Isopentenyl-kaempferol, kaempferol) and target proteins (e.g AKT1, JUN, ESR1, CASP3, MAPK14, RELA) with high degree in the network were associated with in mitogen-activated protein kinase (MAPK) of DNA-binding transcription factor. Moreover, Acoritataninowii Rhizoma might play a significant in the treatment of AD which induced Fluid shear stress and atherosclerosis, Kaposi sarcoma-associated herpesvirus infection, Epstein-Barr virus infection, AGE-RAGE signaling pathway in diabetic complications.Conclusion: The bioactive ingredients and potential mechnism of Acoritataninowii Rhizoma defended AD was analyzed by network pharmacology and molecular docking. This study provided a research basis and scientific evidence for supporting the activities of Acoritataninowii Rhizoma against AD.

scholarly journals Network Pharmacology Deciphering Mechanisms of Volatiles of Wendan Granule for the Treatment of Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jun-feng Liu ◽  
An-na Hu ◽  
Jun-feng Zan ◽  
Ping Wang ◽  
Qiu-yun You ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Senile Dementia ◽  
Quality Standard ◽  
Network Pharmacology ◽  
Gamma Aminobutyric Acid ◽  
Integrated Network

Objective. To explore the mechanisms of the volatiles of Wendan granule (WDG) for the treatment of Alzheimer’s disease, network pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, target fishing, network constructing, pathway analysing, and correlated diseases prediction was applied. Methods. Twelve small molecular compounds of WDG were selected as the objects from 74 volatiles with the relative abundances above 2 %, and their ADME parameters were collected from Traditional Chinese Medicine Systems Pharmacology platform (TCMSP), and the corresponding targets, genes, pathways, and diseases were predicted according to the data provided by TCMSP, DrugBank, Uniport, and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Then the related pathways and correlation analysis were explored by the Kyoto Encyclopedia and Genomes (KEGG) database. Finally, the networks of compound target, target pathway, and pathway disease of WDG were constructed by Cytoscape software. Results. Twelve compounds interacted with 49 targets, of which top three targets were gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), prostaglandin G/H synthase 2 (PGHS-2), and sodium-dependent noradrenaline transporter. Interestingly, these targets were highly associated with depression, insomnia, and Alzheimer’s disease that mainly corresponded to mental and emotional illnesses. Conclusion. The integrated network pharmacology method provides precise probe to illuminate the molecular mechanisms of the main volatiles of WDG for relieving senile dementia related syndromes, which will also facilitate the application of traditional Chinese medicine as an alternative or supplementary to conventional treatments of AD, as well as follow-up studies such as upgrading the quality standard of clinically applied herbal medicine and novel drug development.

Effects of Spaced Retrieval Training on Semantic Memory in Alzheimer's Disease: A Systematic Review

2014 ◽  
Vol 57 (1) ◽  
pp. 247-270 ◽  
Author(s):  
Shiri Oren ◽  
Charlene Willerton ◽  
Jeff Small
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Semantic Memory ◽  
Meta Analysis ◽  
Memory Training ◽  
Point System ◽  
Related Disorder ◽  
Positive Effects ◽  
Spaced Retrieval

Purpose This article reports on a systematic review and meta-analysis of the effects of spaced retrieval training (SRT) on semantic memory in people with Alzheimer's disease (AD) or related disorder. Method An initial systematic database search identified 454 potential studies. After screening and de-duplication, 35 studies that used SRT with the population of interest remained. The authors used an appraisal point system to evaluate the quality of the studies. Twelve of the 35 studies met inclusion and exclusion criteria and passed the appraisal point system cutoff. The 12 studies were classified as Level I and II evidence. Results Although the 12 studies varied in terms of design, methodology, and quality, SRT was shown to have important positive effects on learning semantic information across the included studies. Conclusions The findings indicate that SRT is an effective semantic memory training technique for people with AD, and consequently, recommendations are suggested for implementing SRT in practice settings. Continued research in this domain is also warranted to address limitations and gaps in the current body of research evidence, including variability in SRT protocols, effects of dementia severity on learning outcomes, maintenance effects, generalization, and the role of explicit and implicit learning in SRT.

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