scholarly journals Exploration of the Mechanism and Active Targets of Chinese Herbal Formula, JTTZ, for the Treatment of Type 2 Diabetes with Obesity and Hyperlipidemia Based on Network Pharmacology

2021 ◽  
Author(s):  
Haiyu Zhang ◽  
Xuedong An ◽  
De Jin ◽  
Jiaxing Tian ◽  
Wenke Liu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Therapeutic Targets ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Bile Acid Metabolism ◽  
Ppi Networks ◽  
Kegg Pathway Analysis

Abstract BackgroundPrevious studies have indicated that the JTTZ formula exhibits clinical benefit in T2D with obesity and hyperlipidemia such as lowering blood glucose, blood lipids, weight, and ameliorating symptoms as well as regulating islet function. However, their mechanism of action remains unclear. T2D with obesity and hyperlipidemia is associated with a severely poor management duo to difficulty in achieving the clinical goals and lack of effective multi-targeted therapies. In this study, we explored its potential mechanisms and therapeutic targets by network pharmacology. MethodsThe active ingredients and targets of JTTZ were obtained in the TCMSP, TCMID, TCM Database@Taiwan, PubChem and Swiss Target Prediction. And the therapeutic targets were searched from TTD, DrugBank Database and DisGeNET. Then, topology analysis were used as secondary screens to identify key hubs of the network. Finally, the data was integrated by Cytoscape software to construct a common network module. PPI networks were visualized to identify the interaction of the candidate targets. GO and KEGG pathway analysis were implemented. Rerult: 110 active compounds and 166 candidate targets of JTTZ against T2D with obesity and hyperlipidemia were obtained to construct compound-targets network. And, the therapeutic targets AKT2, RELA, NFKB1 and GSK3B were identified. GO and KEGG pathway analysis indicated that the biological processes related to inflammatory response, insulin secretion, steroid and bile acid metabolism, and 13 pathways mainly including adipocytokine signaling pathway, cAMP signaling pathway and cGMP-PKG signaling pathway were enriched. ConclusionOur data established that JTTZ intervenes with adipose tissue dysfunction via regulating to the adipocytokine (leptin and adiponectin), AMPK signaling pathway, cAMP and cGMP-PKG signaling pathway, inhibits systematic inflammatory response by NF-κB and MAPK signaling pathway, and ameliorates insulin resistance through PI3K/AKT2 pathway, all of which could thus offer a promising therapeutic strategy. In addition, AKT2, RELA, NFKB1 and GSK3B were identified to be regarded as potential therapeutic targets as well.

scholarly journals Mechanisms of Berberine for the Treatment of Atherosclerosis Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xuejiao Xie ◽  
Xingyu Ma ◽  
Siyu Zeng ◽  
Wansi Tang ◽  
Liucheng Xiao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Foam Cell Formation ◽  
Ppi Network ◽  
The Core ◽  
Ppi Networks ◽  
Kegg Pathway Analysis

Atherosclerosis is a common metabolic disease characterized by lipid metabolic disorder. The processes of atherosclerosis include endothelial dysfunction, new endothelial layer formation, lipid sediment, foam cell formation, plaque formation, and plaque burst. Owing to the adverse effects of first-line medications, it is urgent to discover new medications to deal with atherosclerosis. Berberine is one of the most promising natural products derived from traditional Chinese medicine. However, the panoramic mechanism of berberine against atherosclerosis has not been discovered clearly. In this study, we used network pharmacology to investigate the interaction between berberine and atherosclerosis. We identified potential targets related to berberine and atherosclerosis from several databases. A total of 31 and 331 putative targets for berberine and atherosclerosis were identified, respectively. Then, we constructed berberine and atherosclerosis targets with PPI data. Berberine targets network with PPI data had 3204 nodes and 79437 edges. Atherosclerosis targets network with PPI data had 5451 nodes and 130891 edges. Furthermore, we merged the two PPI networks and obtained the core PPI network from the merged PPI network. The core PPI network had 132 nodes and 3339 edges. At last, we performed functional enrichment analyses including GO and KEGG pathway analysis in David database. GO analysis indicated that the biological processes were correlated with G1/S transition of mitotic cells cycle. KEGG pathway analysis found that the pathways directly associated with berberine against atherosclerosis were cell cycle, ubiquitin mediated proteolysis, MAPK signaling pathway, and PI3K-Akt signaling pathway. After combining the results in context with the available treatments for atherosclerosis, we considered that berberine inhibited inflammation and cell proliferation in the treatment of atherosclerosis. Our study provided a valid theoretical foundation for future research.

scholarly journals Network Pharmacology-Based Analysis of the Underlying Mechanism of Hyssopus cuspidatus Boriss. for Antiasthma: A Characteristic Medicinal Material in Xinjiang

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Rongchang Liu ◽  
Yan Mao ◽  
Zhengyi Gu ◽  
Jinhua He
Keyword(s):  
Signaling Pathways ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Interleukin 17 ◽  
Ppi Network ◽  
Active Compounds ◽  
Kegg Pathway Analysis

Background. Hyssopus cuspidatus Boriss. (Shen Xiang Cao (SXC)), a traditional medicine herb in Xinjiang, has a long history of being used by minorities to treat asthma. However, its active antiasthmatic compounds and underlying mechanism of action are still unknown. The aim of this study was to investigate the bioactive compounds and explore the molecular mechanism of SCX in the treatment of asthma using network pharmacology. Methods. The compounds of SCX were collected by a literature search, and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction were used to predict targets and screen active compounds. Moreover, asthma-related targets were obtained based on DisGeNET, Herb, and GeneCards databases, and a protein-protein interaction (PPI) network was built by the STRING database. Furthermore, the topological analysis of the PPI and SXC-compound-target networks were analyzed and established by Cytoscape software. Finally, the RStudio software package was used for carrying out Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. AutoDock tools and AutoDock Vina were used to molecularly dock the active compounds and key targets. Results. A total of 8 active compounds and 258 potential targets related to SXC were predicted, and PPI network screened out key targets, including IL-6, JUN, TNF, IL10, and CXCL8. GO enrichment analysis involved cell responses to reactive oxygen species, oxidative stress, chemical stress, etc. In addition, KEGG pathway analysis showed that SXC effectively treated asthma through regulation of mitogen-activated protein kinases (MAPK) signaling pathways, interleukin 17 (IL-17) signaling pathways, toll-like receptor (TLR) signaling pathways, and tumor necrosis factor (TNF) signaling pathways. Conclusion. The preliminary study that was based on multiple compounds, multiple targets, and multiple pathways provides a scientific basis for further elucidating the molecules involved and the underlying antiasthma-related mechanisms of SXC.

scholarly journals Network analyses of circular RNAs expression profiles and their hub genes in pancreatic ductal adenocarcinoma

2019 ◽  
Author(s):  
Yanyan Tang ◽  
Ping Zhang
Keyword(s):  
Gene Expression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Ductal Adenocarcinoma ◽  
Ppi Network ◽  
Hub Genes ◽  
Kegg Pathway Analysis

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumor in digestive system. CircRNAs involve in lots of biological processes through interacting with miRNAs and their targeted mRNA. We obtained the circRNA gene expression profiles from Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) between PDAC samples and paracancerous tissues. Bioinformatics analyses, including GO analysis, KEGG pathway analysis and PPI network analysis, were conducted for further investigation. We also constructed circRNA‑microRNA-mRNA co-expression network. A total 291 differentially expressed circRNAs were screened out. The GO enrichment analysis revealed that up-regulated DEGs were mainly involved metabolic process, biological regulation, and gene expression, and down-regulated DEGs were involved in cell communication, single-organism process, and signal transduction. The KEGG pathway analysis, the upregulated circRNAs were enriched cGMP-PKG signaling pathway, and HTLV-I infection, while the downregulated circRNAs were enriched in protein processing in endoplasmic reticulum, insulin signaling pathway, regulation of actin cytoskeleton, etc. Four genes were identified from PPI network as both hub genes and module genes, and their circRNA‑miRNA-mRNA regulatory network also be constructed. Our study indicated possible involvement of dysregulated circRNAs in the development of PDAC and promoted our understanding of the underlying molecular mechanisms.

scholarly journals Study on the mechanism of Jiawei Linggui Zhugan Decoction in the treatment of myelodysplastic syndrome based on network pharmacological analysis

2021 ◽  
Vol 3 (3) ◽  
pp. 50-64
Author(s):  
Binyan MO
Keyword(s):  
Myelodysplastic Syndrome ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Biological Function ◽  
Kegg Pathway ◽  
Topological Analysis ◽  
Kegg Pathway Analysis ◽  
Cellular Sensitivity ◽  
Linggui Zhugan Decoction ◽  
Function Enrichment

the research method of network pharmacology is used to explore the material basis and mechanism of modified Linggui Zhugan Decoction in the treatment of myelodysplastic syndrome. Methods: the main active components of 8 traditional Chinese medicines of Jiawei Linggui Zhugan Decoction were searched through tcmsp database, and the target was predicted. The relevant targets of myelodysplastic syndrome were searched through geo database, and the common action targets were obtained by intersection of traditional Chinese medicine targets and disease targets. The core targets were selected by topological analysis with Cytoscape software. Finally, go-bp biological function enrichment and KEGG pathway analysis were carried out based on R software. Results: according to the database analysis, there were 248 active compounds and 3695 targets in the modified Linggui Zhugan decoction, of which 34 were common targets with metabolic syndrome; Through the topological analysis of common targets, 9 core targets were selected. Go-bp biological function enrichment and KEGG pathway analysis found that it can play its therapeutic role through p53, AGE-RAGE, cellular sensitivity, NF KB and other signal pathways. Conclusion: modified Linggui Zhugan decoction may play a therapeutic role through p53 signaling pathway, AGE-RAGE signaling pathway, cellular sensitivity, NF kappa B signaling pathway and cell cycle, so as to provide a new scientific basis for its clinical and basic research.

scholarly journals Network Pharmacology Analysis of the active components and anticancer targets of Rhubarb

2021 ◽  
Author(s):  
Hu Junrui ◽  
Duan Yongqiang ◽  
Cui Gongning ◽  
Luo Qiang ◽  
Xi Shanshan ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Drug Targets ◽  
Target Genes ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Active Components ◽  
Active Compounds ◽  
Cellular Targets ◽  
Kegg Pathway Analysis

AbstractTo investigate the mechanisms and active components governing the anticancer activity of rhubarb.The TCMSP database was screened to identify the active components of rhubarb and Swiss target predictions were generated to predict their cellular targets. TTD and OMIM databases were used to predict tumor-related target genes. "Cytoscape" was used to construct drug targets. PPI network analysis, GO enrichment analysis and KEGG pathway analysis of the key targets were investigated using String and David databases. A total of 33 components and 116 corresponding targets were screened. Amongst them, the key active compounds in rhubarb included emodin, aloe emodin, β-sitosterol, emodin methyl ether and rhein, which were predicted to target TP53, AKT1, STAT3, PIK3CA, HRAS, and VEGFA. GO analysis revealed that the cellular targets clustered into 159 biological processes, including those involved in cellular composition (n=24) and molecular functions (n=42, P<0.01). KEGG pathway analysis revealed 85 (P < 0.01) pathways related to cancer. The active compounds in rhubarb target TP53, AKT1 and PIK3CA. Rhubarb therefore regulates cancer development through an array of biological pathways.

Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway

2015 ◽  
Vol 7 (1) ◽  
pp. 91-101 ◽  
Author(s):  
L. Chen ◽  
J. Yue ◽  
X. Han ◽  
J. Li ◽  
Y. Hu
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Intrauterine Growth Restriction ◽  
Kegg Pathway ◽  
Growth Restriction ◽  
Differentially Expressed ◽  
Intrauterine Growth ◽  
Kegg Pathway Analysis ◽  
Calcium Signaling Pathway

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

scholarly journals Potential Mechanism of Tibetan Medicine Dali in the Treatment of Respiratory Diseases via Network Pharmacology

2021 ◽  
Author(s):  
Yuxin Fan ◽  
Yong Yang ◽  
Yunhong Wang ◽  
Jirui Wang ◽  
Lei Hua ◽  
...  
Keyword(s):  
Cell Growth ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Respiratory Diseases ◽  
Mapk Signaling ◽  
The Body ◽  
Tibetan Medicine ◽  
Network Pharmacology ◽  
Active Components ◽  
Protein Targets

Abstract Background: As a source of Tibetan medicine “Dali”, Rhododendron anthopogonoides Maxim (RAM) has good medically helpful effect on respiratory diseases. However, due to its complex components, there is still a lack of pharmacological and pharmacodynamic research on its active components. Methods: The research method of the network pharmacology was used in this study, to obtain the mechanism of RAM in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The active components of RAM were obtained by searching the relevant database, and the protein targets of each chemical component in RAM were screened by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and PubChem. Then, the protein targets were normalized to the corresponding gene name through UniProt. Meanwhile, genes related to ALI were searched by Online Mendelian Inheritance in Man (OMIM) database, GeneCards database, DrugBank database and DisGeNET database. The “Component-Target-Protein” network was established by Cytoscape software, and the core targets were screened by combining with STRING software. Finally, GO and KEGG enrichment analysis were carried out by David database. Results: Combined with all above results, 92 active components of RAM and 176 gene targets of ALI/ARDS were screened, including 46 common targets, which were related to biological processes such as inflammation, immune and inflammatory response, cell growth and differentiation and apoptosis. Conclusions: It can be concluded through the investigation of network pharmacology that RAM regulates a variety of physiological processes such as cell growth, differentiation, apoptosis and death by activating the Toll-like receptor signaling pathway, TNF signaling pathway, cAMP signaling pathway, MAPK signaling pathway, as well as regulating the inflammatory response of cells, the immune response of the body and promoting the inflammatory cytokines NF‐κB dependent expression and other processes to treat ALI/ARDS. This study revealed the mechanism of RAM multi-component, multi-target and multi-pathway, and provided scientific basis and research ideas for its clinical application.

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 Heatstroke-induced hepatocyte exosomes promote liver injury by activating the NOD-like receptor signaling pathway in mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8216 ◽  
Author(s):  
Yue Li ◽  
Xintao Zhu ◽  
Ming Zhang ◽  
Huasheng Tong ◽  
Lei Su
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Target Cells ◽  
Receptor Signaling ◽  
Kegg Pathway Analysis ◽  
Receptor Signaling Pathway

Background Liver injury is a common and important clinical issue of severe heat stress (HS), which has toxic effects and promotes subsequent multiple organ failure. The pathogenesis of HS-induced liver injury has not been fully elucidated. Passively injured hepatocytes also drive liver injury. Exosomes, extracellular vesicles secreted by hepatocytes as “danger signals,” mediate the intercellular transportation of diverse functional protein cargoes and modulate the biological processes of target cells. However, whether hepatocyte exosomes are involved in HS-induced liver injury has not been reported. The purpose of the current study was to clarify the release of hepatocyte exosomes under HS conditions and to explore their role in mediating HS-induced liver injury. Methods HS was induced in hepatocytes or mice by hyperthermic treatment at 43.0 °C for 1 h. Exosomes from control and HS-exposed hepatocytes were isolated by standard differential ultracentrifugation. The hepatocyte exosomes were characterized, and the differentially expressed proteins of the control and HS exosomes were identified by isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry and subjected to Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Recipient hepatocytes were treated with control or HS exosomes, whereas in vivo, the exosomes were infused into mice. The internalization of HS hepatocyte exosomes by hepatocytes or the liver was tracked. The effect of HS exosomes on the activation of the NOD-like receptor signaling pathway and liver injury was demonstrated in vitro and in vivo. Results HS induced an increase in the release of exosomes from hepatocytes, which were internalized by recipient liver cells in vitro and taken up by the liver in vivo. HS significantly changed the proteomic profiles of hepatocyte exosomes based on the iTRAQ analysis. The KEGG pathway analysis revealed the enrichment of proteins associated with injury and inflammatory signaling pathways, especially the NOD-like receptor signaling pathway, the activity of which was upregulated. Subsequently, the capacity of HS hepatocyte exosomes to activate the NOD-like receptor signaling pathway was verified and found to aggrevate liver damage and inflammation in vitro and in vivo. Conclusions This study is the first preliminary study to demonstrate the induction of acute liver injury by hepatic exosomes in the setting of severe HS and reveals potentially related pathways. These results provide a basis for future research and the identification of new targets for clinical intervention.

scholarly journals Identification of Differential Intestinal Mucosa Transcriptomic Biomarkers for Ulcerative Colitis by Bioinformatics Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fang Cheng ◽  
Qiang Li ◽  
Jinglin Wang ◽  
Fang Zeng ◽  
Kaiping Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immune Response ◽  
Cell Proliferation ◽  
Plasma Membrane ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Extracellular Space ◽  
Kegg Pathway ◽  
Integral Component

Background. Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affect mucosal homeostasis and triggers inappropriate immune response. The purpose of the study was to identify significant biomarkers with potential therapeutic targets and the underlying mechanisms. Methods. The gene expression profiles of GSE48958, GSE73661, and GSE59071 are from the GEO database. Differentially expressed genes (DEGs) were screened by the GEO2R tool. Next, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then, protein-protein interaction (PPI) was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Results. There were a total of 128 common DEGs genes, including 86 upregulated genes enriched in extracellular space, regulation of inflammatory response, chemokine-mediated signaling pathway, response to lipopolysaccharide, and cell proliferation, while 42 downregulated genes enriched in the integral component of the membrane, the integral component of the plasma membrane, apical plasma membrane, symporter activity, and chloride channel activity. The KEGG pathway analysis results demonstrated that DEGs were particularly enriched in cytokine-cytokine receptor interaction, TNF signaling pathway, chemokine signaling pathway, pertussis, and rheumatoid arthritis. 18 central modules of the PPI networks were selected with Cytotype MCODE. Furthermore, 18 genes were found to significantly enrich in the extracellular space, inflammatory response, chemokine-mediated signaling pathway, TNF signaling pathway, regulation of cell proliferation, and immune response via reanalysis of DAVID. Conclusion. The study identified DEGs, key target genes, functional pathways, and pathway analysis of UC, which may provide potential molecular targets and diagnostic biomarkers for UC.

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