scholarly journals A Bioinformatics Investigation into the Pharmacological Mechanisms of Sodium-Glucose Co-transporter 2 Inhibitors on Diabetes Mellitus and Heart Failure based on Network Pharmacology

2021 ◽  
Author(s):  
Ziling Mai ◽  
Huanqiang Li ◽  
Guanzhong Chen ◽  
Enzhao Chen ◽  
Liwei Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Signaling Pathway ◽  
Drug Target ◽  
Kinase Inhibitor ◽  
Target Prediction ◽  
Mapk Signaling ◽  
Mendelian Inheritance ◽  
Sglt2 Inhibitors ◽  
Network Pharmacology ◽  
Pharmacological Mechanism

Abstract BackgroundDiabetes mellitus (DM) is a major risk factor for the development of heart failure (HF). Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated consistent benefits in the reduction of hospitalization for HF in patients with DM. However, the pharmacological mechanism is not clear. To investigate the mechanisms of SGLT2 inhibitors on HF and DM, we performed target prediction and network analysis by network pharmacology method.Material/MethodsWe selected targets of SGLT2 inhibitors according to SwissTargetPrediction and DrugBank databases and collected therapeutic targets on HF and DM from the Human Gene (GeneCards) and Human Mendelian Inheritance (OMIM) databases. The “Drug-Target” and “Drug-Target-Disease” networks were constructed by using Cytoscape_v3.6.1. Then the protein-protein interaction (PPI) was analyzed by using the String database. Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to investigate by using Bioconductor tool for analysis.ResultsThere were 125 effective targets among SGLT2 inhibitors, HF and DM. Through further screening and analyzing, 33 core targets were obtained, such as SRC, MAPK1, NARS, MAPK3 and EGFR. And it is predicted that Rap1 signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications and other signaling pathways were involved in the treatment of HF and DM by SGLT2 inhibitors.ConclusionsOur study elucidated the possible mechanisms of SGLT2 inhibitors from a systemic and holistic perspective based on pharmacological networks. The key targets and pathways will provide new insights for further research on the pharmacological mechanism of SGLT2 inhibitors in the therapy of HF and DM.

scholarly journals A Bioinformatics Investigation into the Pharmacological Mechanisms of Sodium-Glucose Co-transporter 2 Inhibitors in Diabetes Mellitus and Heart Failure Based on Network Pharmacology

2021 ◽  
Author(s):  
Ziling Mai ◽  
Huanqiang Li ◽  
Guanzhong Chen ◽  
Enzhao Chen ◽  
Liwei Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Signaling Pathway ◽  
Drug Target ◽  
Kinase Inhibitor ◽  
Target Prediction ◽  
Mapk Signaling ◽  
Sglt2 Inhibitors ◽  
Network Pharmacology ◽  
Pharmacological Mechanism

Abstract Purpose Diabetes mellitus (DM) is a major risk factor for the development of heart failure (HF). Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated consistent benefits in the reduction of hospitalization for HF in patients with DM. However, the pharmacological mechanism is not clear. To investigate the mechanisms of SGLT2 inhibitors in DM with HF, we performed target prediction and network analysis by a network pharmacology method. Methods We selected targets of SGLT2 inhibitors and DM status with HF from databases and studies. The “Drug-Target” and “Drug-Target-Disease” networks were constructed using Cytoscape. Then the protein–protein interaction (PPI) was analyzed using the STRING database. Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to investigate using the Bioconductor tool for analysis. Results There were 125 effective targets between SGLT2 inhibitors and DM status with HF. Through further screening, 33 core targets were obtained, including SRC, MAPK1, NARS, MAPK3 and EGFR. It was predicted that the Rap1 signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications and other signaling pathways were involved in the treatment of DM with HF by SGLT2 inhibitors. Conclusion Our study elucidated the possible mechanisms of SGLT2 inhibitors from a systemic and holistic perspective based on pharmacological networks. The key targets and pathways will provide new insights for further research on the pharmacological mechanism of SGLT2 inhibitors in the treatment of DM with HF.

scholarly journals Exploring the Mechanism of Quercetin for the Treatment of Atrial Fibrillation by GEO Gene Chip Combined with Network Pharmacology and Molecular Docking

2022 ◽  
Author(s):  
Xin Tan ◽  
Wei Xian ◽  
Xiaorong Li ◽  
Yongfeng Chen ◽  
Jiayi Geng ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Prediction ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Network Pharmacology ◽  
Therapeutic Drug ◽  
Geo Database

Abstract Atrial fibrillation (AF) is a common atrial arrhythmia for which there is no specific therapeutic drug. Quercetin (Que) has been used to treat cardiovascular diseases such as arrhythmias. In this study, we explored the mechanism of action of Que in AF using network pharmacology and molecular docking. The chemical structure of Que was obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank, STITCH, Binding DB, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF and normal tissue by GEO database differentially expressed genes by GEO database. The top targets were IL6, VEGFA, JUN, MMP9 and EGFR, and Que for AF treatment might involve the lipid and atherosclerosis pathway, the role of AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. In addition, molecular docking showed that Que binds strongly to key targets and is differentially expressed in AF. This study systematically elucidated the key targets of Que treatment for AF and the specific mechanisms, providing a new direction for further basic experimental exploration and clinical treatment.

scholarly journals Exploring the Mechanism of Quercetin for the Treatment of Atrial Fibrillation by Geo Gene Chip Combined With Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
tan xin ◽  
Wei Xian ◽  
Xiaorong Li ◽  
Yongfeng Chen ◽  
Jiayi Geng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Mechanism Of Action ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Network Pharmacology ◽  
Chemical Structures ◽  
Drug Mechanism

Abstract PurposeAtrial fibrillation (AF) is a common atrial arrhythmia. Quercetin (Que) has some advantages in the treatment of cardiovascular disease arrhythmias, but its specific drug mechanism of action needs further investigation. To explore the mechanism of action of Que in AF, core target speculation and analysis were performed using network pharmacology and molecular docking methods.MethodsQue chemical structures were obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank , STITCH, Binding DB, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF from normal tissues by GEO database differentially expressed genes. Then, the intersecting genes were obtained by online Wayne mapping tool. The intersection genes were introduced into the top five targets selected for molecular docking via protein-protein interaction (PPI) network to verify the binding activity between Que and the target proteins. GO and KEGG enrichment analysis of the intersected genes using program R was performed to further screen for key genes and key pathways.ResultsThere were 65 effective targets for Que and AF. Through further screening, the top 5 targets were IL6, VEGFA, JUN, MMP9 and EGFR. Que treatment of AF may involve signaling pathways such as lipid and atherosclerosis pathway, AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking suggests that Que has strong binding to key targets.ConclusionThis study systematically elucidates the key targets of Que treatment for AF and the specific mechanisms through network pharmacology as well as molecular docking, providing a new direction for further basic experimental exploration and clinical treatment.

scholarly journals A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of Atherosclerosis

2021 ◽  
Author(s):  
Ki Kwang Oh ◽  
Md. Adnan ◽  
Dong Ha Cho
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Ganoderma Lucidum ◽  
Mapk Signaling ◽  
Mendelian Inheritance ◽  
Chronic Inflammatory Disease ◽  
Mapk Signaling Pathway ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Overlapping Genes

Abstract Background: Ganoderma lucidum (GL) is known as a potent alleviator against chronic inflammatory disease like atherosclerosis (AS), but its critical bioactive compounds and their mechanisms against AS have not been unveiled. This research aimed to identify the key compounds(s) and mechanism(s) of GL against AS through network pharmacology.Methods: The compounds from GL were identified by gas chromatography-mass spectrum (GC-MS), and SwissADME screened their physicochemical properties. Then, the gene(s) associated with the screened compound(s) or AS related genes were identified by public databases, and we selected the overlapping genes using a Venn diagram. The networks between overlapping genes and compounds were visualized, constructed, and analyzed by RStudio. Finally, we performed molecular docking test (MDT) to identify key gene(s), compound(s) on AutoDockVina.Results: A total of 35 compounds in GL was detected via GC-MS, and 34 compounds (accepted by the Lipinski's rule) were selected as drug-like compounds (DLCs). A total of 34 compounds were connected to the number of 785 genes and 2,606 AS-related genes were identified by DisGeNET and Online Mendelian Inheritance in Man (OMIM). The final 98 overlapping genes were extracted between the compounds-genes network and AS-related genes. On Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, the number of 27 signaling pathways were sorted out, and a hub signaling pathway (MAPK signaling pathway), a core gene (PRKCA), and a key compound (Benzamide, 4-acetyl-N-(2,6-dimethylphenyl)) were selected among the 27 signaling pathways via MDT. Conclusion: Overall, we found that the identified 3 DLCs from GL have potent anti-inflammatory efficacy, improving AS by inactivating the MAPK signaling pathway.

scholarly journals Exploring the Pharmacological Mechanism of Cassiae Semen a Cting on Cataracts Based on a Network Pharmacology Approach

2020 ◽  
Author(s):  
Ying Zhong ◽  
Youfa Fang
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Pharmacological Mechanism ◽  
Ppi Networks ◽  
Target Network ◽  
Central Network

Abstract BackgroundCassiae Semen (CS) is one of the most well-known herbs used in the treatment of cataracts in China. However, the potential mechanisms of its anti-cataracts effects have not been fully explored.MethodThe active compounds of CS were obtained from TCMSP database, and their targets were retrieved from the TCMSP, STITCH and DrugBank databases. Cataracts related target genes were identified from the GeneCard, Malacard, and OMIM databases. GO and KEGG analysis were performed using DAVID online tools, and Cytoscape were used to construct compound-targets network and protein-protein interaction (PPI) networks, cluster analysis were carried out using MCODE plugin for Cytoscape.ResultsWe obtained 13 active compounds from CS and 105 targets in total to construct a compound-target network, which indicated that emodin, stigmastero, and rhein served as the main ingredients in CS. A total of 238 cataracts related targets were identified from public databases. PPI networks of compound targets and cataract-related targets were constructed and merged to obtained the central network, enrichment analysis showed 50 key targets in the central network enriched in several important signaling pathways, such as thyroid hormone signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway. The top 4 genes with higher degree in the central network were TP53, HSP90, ESR1, EGFR, indicating their important roles in the treatment of cataracts.ConclusionsThe present study systematically revealed the multi-target mechanisms of CS on cataracts using network pharmacology approach, and provided indications for further mechanistic studies and also for the development of CS as a potential treatment for cataracts patients.

scholarly journals To Explore the Mechanism and Equivalent Molecular Group of Fuxin Mixture in Treating Heart Failure Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yi-ding Yu ◽  
Yi-ping Xiu ◽  
Yang-fan Li ◽  
Yi-tao Xue
Keyword(s):  
Heart Failure ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
New Drugs ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Nf Kappa B ◽  
Vegf Signaling ◽  
Molecular Group

Fuxin mixture (FXHJ) is a prescription for the treatment of heart failure. It has been shown to be effective in clinical trials, but its active ingredients and mechanism of action are not completely clear, which limits its clinical application and international promotion. In this study, we used network pharmacology to find, conclude, and summarize the mechanism of FXHJ in the treatment of heart failure. From FXHJ, we found 39 active ingredients and 47 action targets. Next, we constructed the action network and was conducted enrichment analysis. The results showed that FXHJ mainly treated heart failure by regulating the MAPK signaling pathway, PI3KAkt signaling pathway, cAMP signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, and the apoptotic signaling molecule BCL2. Through the research method of network pharmacology, this study summarized the preliminary experiments of the research group and revealed the probable mechanism of FXHJ in the treatment of heart failure to a certain extent, which provided some ideas for the development of new drugs.

scholarly journals Studies of the Anti-Diabetic Mechanism of Pueraria lobata Based on Metabolomics and Network Pharmacology

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1245
Author(s):  
Shu Zhang ◽  
Qi Ge ◽  
Liang Chen ◽  
Keping Chen
Keyword(s):  
Signaling Pathway ◽  
Diabetes Complications ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pueraria Lobata ◽  
Insulin Deficiency ◽  
Active Ingredients ◽  
Foxo Signaling Pathway ◽  
Anti Inflammation

Diabetes mellitus (DM), as a chronic disease caused by insulin deficiency or using obstacles, is gradually becoming a principal worldwide health problem. Pueraria lobata is one of the traditional Chinese medicinal and edible plants, playing roles in improving the cardiovascular system, lowering blood sugar, anti-inflammation, anti-oxidation, and so on. Studies on the hypoglycemic effects of Pueraria lobata were also frequently reported. To determine the active ingredients and related targets of Pueraria lobata for DM, 256 metabolites were identified by LC/MS non targeted metabonomics, and 19 active ingredients interacting with 51 DM-related targets were screened. The results showed that puerarin, quercetin, genistein, daidzein, and other active ingredients in Pueraria lobata could participate in the AGE-RAGE signaling pathway, insulin resistance, HIF-1 signaling pathway, FoxO signaling pathway, and MAPK signaling pathway by acting on VEGFA, INS, INSR, IL-6, TNF and AKT1, and may regulate type 2 diabetes, inflammation, atherosis and diabetes complications, such as diabetic retinopathy, diabetic nephropathy, and diabetic cardiomyopathy.

scholarly journals A Network Pharmacology Approach to Explore Mechanism of Action of Longzuan Tongbi Formula on Rheumatoid Arthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
An Huang ◽  
Gang Fang ◽  
Yuzhou Pang ◽  
Zongran Pang
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Active Rheumatoid Arthritis ◽  
Trp Channels ◽  
Network Pharmacology ◽  
Mtor Signaling Pathway ◽  
Active Ingredients ◽  
Major Pathway ◽  
Pharmacological Mechanism ◽  
Ppar Signaling

Longzuan Tongbi Formula (LZTB) is an effective proved prescription in Zhuang medicine for treating active rheumatoid arthritis (RA). However, its active ingredients, underlying targets, and pharmacological mechanism are still not clear in treating RA. We have applied network pharmacology to study LZTB and found that 8 herbs in LZTB and 67 compounds in the 8 herbs are involved in the regulation of RA-related genes; we have conducted pathway analysis of overlapping genes and found that 7 herbs participate in the regulations of 24 pathways associated with RA and that 5 herbs in the 7 herbs and 25 compounds in the 5 herbs participate in the regulation of hsa05323 (rheumatoid arthritis). The results indicated that all herbs in LZTB and some compounds in those herbs participate in the treatment of RA; 25 compounds are main active ingredients and hsa05323 (rheumatoid arthritis) is the major pathway in the treatment of RA. We have also found that three pathways (inflammatory mediator regulation of TRP channels, PPAR signaling pathway, and mTOR signaling pathway) might have some effect on the treatment of RA.

scholarly journals Network Pharmacology of Yougui Pill Combined with Buzhong Yiqi Decoction for the Treatment of Sexual Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yangyun Wang ◽  
Wandong Yu ◽  
Chaoliang Shi ◽  
Wei Jiao ◽  
Junhong Li ◽  
...  
Keyword(s):  
Sexual Dysfunction ◽  
Signaling Pathway ◽  
Herbal Medicines ◽  
Mapk Signaling ◽  
Glycyrrhetinic Acid ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Chemical Components ◽  
Target Proteins ◽  
Yougui Pill

Purpose. We aimed to find the possible key targets of Yougui pill and Buzhong Yiqi decoction for the treatment of sexual dysfunction. Materials and Methods. The composition of Yougui pill combined with Buzhong Yiqi decoction was obtained, and its effective components of medicine were screened using ADME; the component target proteins were predicted and screened based on the TCMSP and BATMAN databases. Target proteins were cross-validated using the CTD database. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins using the Cytoscape plugin ClueGO + CluePedia and the R package clusterProfiler, respectively. Subsequently, protein-protein interaction (PPI) analyses were conducted using the STRING database. Finally, a pharmacological network was constructed. Results. The pharmacological network contained 89 nodes and 176 relation pairs. Among these nodes, there were 12 for herbal medicines (orange peel, licorice, Eucommia, Aconite, Astragalus, Chinese wolfberry, yam, dodder seed, ginseng, Cornus officinalis, Rehmannia, and Angelica), 9 for chemical components (18-beta-glycyrrhetinic acid, carvacrol, glycyrrhetinic acid, higenamine, nobilin, quercetin, stigmasterol, synephrine, and thymol), 62 for target proteins (e.g., NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53), and 6 for pathways (MAPK signaling pathway, proteoglycans in cancer, dopaminergic synapse, thyroid hormone signaling pathway, cAMP signaling pathway, and neuroactive ligand-receptor interaction). Conclusion. NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53 may be important targets for the key active elements in the decoction combining Yougui pill and Buzhong Yiqi. Furthermore, these target proteins are relevant to the treatment of sexual dysfunction, probably via pathways associated with cancer and signal transduction.

scholarly journals Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

2020 ◽  
Vol 11 ◽  
Author(s):  
Yanni Lai ◽  
Qiong Zhang ◽  
Haishan Long ◽  
Tiantian Han ◽  
Geng Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Influenza A ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
New Drugs ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Components ◽  
Compound Screening

Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear.Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology.Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology.Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05).Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.

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