Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer’s Disease

Shen, Yanjia; Zhang, Baoyue; Pang, Xu; Yang, Ran; Chen, Miao; Zhao, Jiaying; Wang, Jinhua; Wang, Zhe; Yu, Ziru; Wang, Yuehua; Li, Li; Liu, Ailin; Du, Guanhua

doi:10.3389/fphar.2020.595254

Cited by 23 publications

(15 citation statements)

References 34 publications

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“…Molecular docking was performed to determine the binding affinity of the compounds of HQSJZD with AChE. Through a tool used to edit binding sites and search for binding sites that involve receptors and ligands based on information from the RCSB protein database (PDB) ( http://www.pdb ) or the sites of the original ligands of proteins, crystal structures were obtained [ 30 ]. Then, 3D structures of acetylcholinesterase (AChE) (PDB Code: 4ey7) were got from the PDB database in PDB format by setting the organism to “ Homo sapiens .” Three-dimensional conformers of the candidate compounds were gained from the PubChem database ( https://pubchem.ncbi.nlm.nih.gov/ ) in MOL format [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

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

Zhang

Shi

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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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.

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Section: Methodsmentioning

confidence: 99%

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

Zhang

Shi

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…The Database for Annotation, Visualization, and Integrated Discovery (DAVID) (Shen et al, 2020) (https://david.ncifcrf. gov/summary.jsp) was employed for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses of the corresponding targets of each of the identified ZZHPD components.…”

Section: Pathway Analysismentioning

confidence: 99%

Integrated Network Pharmacology Analysis and Experimental Validation to Investigate the Mechanism of Zhi-Zi-Hou-Po Decoction in Depression

Bai

Zhang

et al. 2021

Front. Pharmacol.

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Zhi-Zi-Hou-Po Decoction (ZZHPD) is a well-known traditional Chinese medicine (TCM) that has been widely used in depression. However, the antidepressant mechanism of ZZHPD has not yet been fully elucidated. The purpose of this study was to explore the pharmacological mechanisms of ZZHPD acting on depression by combining ultra flow liquid chromatography with quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF/MS) and network pharmacology strategy. The chemical components of ZZHPD were identified using UFLC-Q-TOF/MS, while the potential drug targets and depression-related targets were collected from databases on the basis of the identified compounds of ZZHPD. Protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were used to unravel potential antidepressant mechanisms. The predicted antidepressant targets from the pharmacology-based analysis were further verified in vivo. As a result, a total of 31 chemical compounds were identified by UFLC-Q-TOF/MS; 514 promising drug targets were mined by using the Swiss Target Prediction; and 527 depression-related target genes were pinpointed by the GeneCards and OMIM databases. STRING database and Cytoscape’s topological analysis revealed 80 potential targets related to the antidepressant mechanism of ZZHPD. The KEGG pathway analysis revealed that the antidepressant targets of ZZHPD were mainly involved in dopaminergic synapse, serotonin synapse, cAMP, and mTOR signaling pathways. Furthermore, based on the animal model of depression induced by chronic corticosterone, the regulatory effects of ZZHPD on the expression of MAOA, MAOB, DRD2, CREBBP, AKT1, MAPK1, HTR1A, and GRIN2B mRNA levels as well as the cAMP signaling pathway and monoaminergic metabolism were experimentally verified in rats. Our study revealed that ZZHPD is expounded to target various genes and pathways to perform its antidepressant effect.

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“…Two kinds of networks in this study were established using Cytoscape 3.6.0 software: compound-target network (C-T network) and target-disease network (T-D network) 44 . C-T network was composed of bioactive compounds and their potential targets, which was built to reveal the drug-target interactions.…”

Section: Network Construction and Analysismentioning

confidence: 99%

Anti-inflammatory Properties of Fangji Huangqi Tang: Discovery Based on Network Pharmacology, Molecular Docking and Arrowsmith Tools

Jiang¹,

Han²,

Liu³

et al. 2021

Preprint

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Fangji Huangqi Tang (FHT) is a classical formula widely used in Chinese clinical practice. In this study, a creative application of FHT for inflammation has been identified by network pharmacology-based framework. Specifically, a total of 17 bioactive compounds including 42 potential targets of FHT, and 205 related targets involved in inflammation were retrieved from mainstream databases and subjected to network analysis. 13 intersection targets indicated the principal elements linked to inflammation therapy. Top terms of Gene Ontology (GO) analysis were identified, while 7 related signaling pathways were revealed by Kyoto Encyclopedia of Genes and Genomes (KEGG) results. Subsequently, Calycosin-PTGS2 with tight binding affinity (BA) was manifested by molecular docking as the critical compound-target couple. Meaningful links between Calycosin and inflammation were implied through Arrowsmith, which overlapped with the findings in enrichment analysis, such as MAPK, NF-κB that could be regulators of PTGS2. In summary, the present study explored the potential targets and signaling pathways of FHT against inflammation, which may help to illustrate the mechanisms responsible for the action of FHT and provide a better understanding of its anti-inflammatory effects.

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Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer’s Disease

Cited by 23 publications

References 34 publications

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

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

Integrated Network Pharmacology Analysis and Experimental Validation to Investigate the Mechanism of Zhi-Zi-Hou-Po Decoction in Depression

Anti-inflammatory Properties of Fangji Huangqi Tang: Discovery Based on Network Pharmacology, Molecular Docking and Arrowsmith Tools

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