Unraveling the action mechanism of Buyang Huanwu Tang (BYHWT) for Cerebral Ischemia by Systematic Pharmacological Methodology

2020 ◽  
Vol 23 ◽  
Author(s):  
Shi-tang Ma ◽  
Ning Zhang ◽  
Ge Hong ◽  
Cheng-tao Feng ◽  
Sheng-wei Hong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Virtual Screening ◽  
Signaling Pathways ◽  
Bioactive Compounds ◽  
Enrichment Analysis ◽  
Material Base ◽  
Lead Discovery ◽  
Binding Effect ◽  
Bioactive Ingredients ◽  
Compound Target

Background: Buyang Huanwu Tang (BYHWT) and relevant Traditional Chinese medicine (TCM) has its unique advantages in the treatment of cerebral ischemia. However, its pharmacological mechanism have not been fully explained. Objective: Base on the multi-component, also the entire disease network targets, the present study set out to identify major bioactive ingredients, key disease targets, and pathways of BYHWT against cerebral ischemia disease by systematic pharmacological methodology. Methods: Both the bioactive compounds from the BYHWT and the positive drugs against cerebral ischemia were fully investigated. The binding targets of the positive drugs were then obtained. A virtual screening protocol was then used to highlight the compound-target interaction. And network was constructed to visual the compound-target binding effect after docking analysis. Moreover，the targets enrichment analysis for biological processes and pathways were revealed to further explore the function of bio-targets protein gene and its role in the signal pathway. Results: A total of 382 active ingredients of the BYHWT and 23 candidate disease targets were identified. Virtual screening results indicated that multiple bioactive compounds targeted multiple proteins. Each compounds act on one or more targets. The mechanisms were linked to 20 signaling pathways, and the key mechanism was related to serotonergic synapse, calcium signaling pathway and camp signaling pathways. Conclusion: The present study explored the bioactive ingredients and mechanisms of BYHWT against cerebral ischemia by systematic pharmacological methodology. the novel methodology would provide a reference for the lead discovery of precursors, disease mechanism and material base for TCM.

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

2021 ◽  
Author(s):  
Qingtao Jiang ◽  
Lei Han ◽  
Xin Liu ◽  
Feng Zhang
Keyword(s):  
Gene Ontology ◽  
Molecular Docking ◽  
Signaling Pathways ◽  
Tight Binding ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Classical Formula ◽  
Anti Inflammatory ◽  
Principal Elements ◽  
Compound Target

Abstract 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.

scholarly journals Network Pharmacology-Based Prediction of Bioactive Compounds and Potential Targets of Wenjing Decoction for Treatment of Endometriosis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yu-nan Liu ◽  
Xiao-jing Hu ◽  
Bei Liu ◽  
Yu-jie Shang ◽  
Wen-ting Xu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Bioactive Compounds ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Inflammatory Disorder

Endometriosis is a chronic estrogen-dependent inflammatory disorder that negatively affects the quality of life in women. The Wenjing decoction (WJD) is a traditional Chinese medicine that has been shown to have a therapeutic effect on endometriosis. Our study systematically explored the mechanism of WJD against endometriosis using a network pharmacology approach. Potentially bioactive compounds of WJD and their possible targets were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The protein-protein interaction network and herbs-compounds-genes multinetwork were constructed using Cytoscape for visualization. Subsequently, the signaling pathways of common targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and molecular docking was performed using PyRx software. In total, 48 common targets were screened, such as IL6 and ESR1, which were related to inflammation and the endocrine system. The top five bioactive compounds were quercetin, kaempferol, wogonin, beta-sitosterol, and stigmasterol. KEGG enrichment analysis revealed 65 pathways containing inflammatory- and endocrine-related signaling pathways, such as the “TNF signaling pathway” and the “estrogen signaling pathway.” Taken together, the results of our network pharmacology analysis predicted that certain active ingredients of WJD might treat endometriosis by regulating inflammation and/or endocrine, which provided references for further understanding and exploration of WJD on endometriosis.

scholarly journals Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yi Chen ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathways ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemic

Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained.Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR.Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05).Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

scholarly journals AB0005 IDENTIFICATION OF KEY GENES AND PATHWAYS FOR PSORIASIS BASED ON GEO DATABASES BY BIOINFORMATICS ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1037.2-1038
Author(s):  
X. Sun ◽  
S. X. Zhang ◽  
S. Song ◽  
T. Kong ◽  
C. Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Shanxi Province ◽  
Receptor Interaction ◽  
Term Therapy ◽  
Pathway Enrichment Analysis ◽  
Key Genes

Background:Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both, and also has a strong genetic predisposition and autoimmune pathogenic traits1. The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. And it’s also a chronic relapsing disease, which often necessitates a long-term therapy2.Objectives:To investigate the molecular mechanisms of psoriasis and find the potential gene targets for diagnosis and treating psoriasis.Methods:Total 334 gene expression data of patients with psoriasis research (GSE13355 GSE14905 and GSE30999) were obtained from the Gene Expression Omnibus database. After data preprocessing and screening of differentially expressed genes (DEGs) by R software. Online toll Metascape3 was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Interactions of proteins encoded by DEGs were discovered by Protein-protein interaction network (PPI) using STRING online software. Cytoscape software was utilized to visualize PPI and the degree of each DEGs was obtained by analyzing the topological structure of the PPI network.Results:A total of 611 DEGs were found to be differentially expressed in psoriasis. GO analysis revealed that up-regulated DEGs were mostly associated with defense and response to external stimulus while down-regulated DEGs were mostly associated with metabolism and synthesis of lipids. KEGG enrichment analysis suggested they were mainly enriched in IL-17 signaling, Toll-like receptor signaling and PPAR signaling pathways, Cytokine-cytokine receptor interaction and lipid metabolism. In addition, top 9 key genes (CXCL10, OASL, IFIT1, IFIT3, RSAD2, MX1, OAS1, IFI44 and OAS2) were identified through Cytoscape.Conclusion:DEGs of psoriasis may play an essential role in disease development and may be potential pathogeneses of psoriasis.References:[1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31].[2]Zhang YJ, Sun YZ, Gao XH, et al. Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis. Mol Med Rep 2019;20(1):225-35. doi: 10.3892/mmr.2019.10241 [published Online First: 2019/05/23].[3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

Characterization of Gcf2/Lrrfip1 in experimental cerebral ischemia and its role as a modulator of Akt, mTOR and β-catenin signaling pathways

Neuroscience ◽  
2014 ◽  
Vol 268 ◽  
pp. 48-65 ◽  
Author(s):  
C. Gubern ◽  
S. Camós ◽  
O. Hurtado ◽  
R. Rodríguez ◽  
V.G. Romera ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathways ◽  
Experimental Cerebral Ischemia

From Virtual Screening to Bioactive Compounds by Visualizing and Clustering of Chemical Space

2011 ◽  
Vol 31 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Alexander Klenner ◽  
Volker Hähnke ◽  
Tim Geppert ◽  
Petra Schneider ◽  
Heiko Zettl ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Bioactive Compounds ◽  
Chemical Space

scholarly journals Elucidation of the mechanisms and molecular targets of Qishen Yiqi formula for the treatment of pulmonary arterial hypertension using a bioinformatics/network topology-based strategy

2020 ◽  
Vol 23 ◽  
Author(s):  
Peiliang Wu ◽  
Xiaona Xie ◽  
Mayun Chen ◽  
Junwei Sun ◽  
Luqiong Cai ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Network Topology ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Bioactive Ingredients ◽  
Pulmonary Arterial

Background and Objective: Qishen Yiqi formula (QSYQ) is used to treat cardiovascular disease in the clinical practice of traditional Chinese medicine. However, few studies have explored whether QSYQ affects pulmonary arterial hypertension (PAH), and the mechanisms of action and molecular targets of QSYQ for the treatment of PAH are unclear. A bioinformatics/network topology-based strategy was used to identify the bioactive ingredients, putative targets, and molecular mechanisms of QSYQ in PAH. Methods: A network pharmacology-based strategy was employed by integrating active component gathering, target prediction, PAH gene collection, network topology, and gene enrichment analysis to systematically explore the multicomponent synergistic mechanisms. Results: In total, 107 bioactive ingredients of QSYQ and 228 ingredient targets were identified. Moreover, 234 PAH-related differentially expressed genes with a |fold change| >2 and an adjusted P value < 0.005 were identified between the PAH patient and control groups, and 266 therapeutic targets were identified. The pathway enrichment analysis indicated that 85 pathways, including the PI3K-Akt, MAPK, and HIF-1 signaling pathways, were significantly enriched. TP53 was the core target gene, and 7 other top genes (MAPK1, RELA, NFKB1, CDKN1A, AKT1, MYC, and MDM2) were the key genes in the gene-pathway network based on the effects of QSYQ on PAH. Conclusion: An integrative investigation based on network pharmacology may elucidate the multicomponent synergistic mechanisms of QSYQ in PAH and lay a foundation for further animal experiments, human clinical trials and rational clinical applications of QSYQ.

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