Integrated phytochemical analysis based on UHPLC-LTQ–Orbitrap and network pharmacology approaches to explore the potential mechanism of Lycium ruthenicum Murr. for ameliorating Alzheimer's disease

2020 ◽  
Vol 11 (2) ◽  
pp. 1362-1372 ◽  
Author(s):  
Zhiqiang Luo ◽  
Guohua Yu ◽  
Xinjing Chen ◽  
Yang Liu ◽  
Yating Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Pharmacology ◽  
Phytochemical Analysis ◽  
Potential Mechanism ◽  
Lycium Ruthenicum ◽  
Lycium Ruthenicum Murr

Exploring the potential mechanism of Lycium ruthenicum Murr. for ameliorating Alzheimer's disease using comprehensive UHPLC-LTQ–Orbitrap based phytochemical analysis and network pharmacology approaches.

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.

Phytochemicals for drug discovery in Alzheimer’s disease: In silico Advances

2020 ◽  
Vol 26 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Design ◽  
In Silico ◽  
Drug Targets ◽  
Development Process ◽  
Phytochemical Analysis ◽  
Computational Drug Design ◽  
Novel Drugs ◽  
Game Changer

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

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.

Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer's disease

2018 ◽  
Vol 16 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Xiao-Cong PANG ◽  
De KANG ◽  
Jian-Song FANG ◽  
Ying ZHAO ◽  
Lv-Jie XU ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Pharmacology ◽  
Chinese Herbal

scholarly journals Network Pharmacology Analysis and Molecular Characterization of the Herbal Medicine Formulation Qi-Fu-Yin for the Inhibition of the Neuroinflammatory Biomarker iNOS in Microglial BV-2 Cells: Implication for the Treatment of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Fung Yin Ngo ◽  
Weiwei Wang ◽  
Qilei Chen ◽  
Jia Zhao ◽  
Hubiao Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Selective Inhibition ◽  
Network Pharmacology ◽  
Herbal Formula ◽  
Active Compounds ◽  
Protein Targets ◽  
Blotting Technique ◽  
Cox 2 ◽  
Angelicae Sinensis

Aberrant microglial activation drives neuroinflammation and neurodegeneration in Alzheimer’s disease (AD). The present study is aimed at investigating whether the herbal formula Qi-Fu-Yin (QFY) could inhibit the inflammatory activation of cultured BV-2 microglia. A network pharmacology approach was employed to predict the active compounds of QFY, protein targets, and affected pathways. The representative pathways and molecular functions of the targets were analyzed by Gene Ontology (GO) and pathway enrichment. A total of 145 active compounds were selected from seven herbal ingredients of QFY. Targets (e.g., MAPT, APP, ACHE, iNOS, and COX-2) were predicted for the selected active compounds based on the relevance to AD and inflammation. As a validation, fractions were sequentially prepared by aqueous extraction, ethanolic precipitation, and HPLC separation, and assayed for downregulating two key proinflammatory biomarkers iNOS and COX-2 in lipopolysaccharide- (LPS-) challenged BV-2 cells by the Western blotting technique. Moreover, the compounds of QFY in 90% ethanol downregulated iNOS in BV-2 cells but showed no activity against COX-2 induction. Among the herbal ingredients of QFY, Angelicae Sinensis Radix and Ginseng Radix et Rhizoma contributed to the selective inhibition of iNOS induction. Furthermore, chemical analysis identified ginsenosides, especially Rg3, as antineuroinflammatory compounds. The herbal formula QFY may ameliorate neuroinflammation via downregulating iNOS in microglia.

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.

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