scholarly journals Mechanism of Radix Rhei Et Rhizome Intervention in Cerebral Infarction: A Research Based on Chemoinformatics and Systematic Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Wang Xiang ◽  
Zhiyong Long ◽  
Jinsong Zeng ◽  
Xiaofei Zhu ◽  
Mengxia Yuan ◽  
...  

Objective. To explore the therapeutic targets, network modules, and coexpressed genes of Radix Rhei Et Rhizome intervention in cerebral infarction (CI), and to predict significant biological processes and pathways through network pharmacology. To explore the differential proteins of Radix Rhei Et Rhizome intervention in CI, conduct bioinformatics verification, and initially explain the possible therapeutic mechanism of Radix Rhei Et Rhizome intervention in CI through proteomics. Methods. The TCM database was used to predict the potential compounds of Radix Rhei Et Rhizome, and the PharmMapper was used to predict its potential targets. GeneCards and OMIM were used to search for CI-related genes. Cytoscape was used to construct a protein-protein interaction (PPI) network and to screen out core genes and detection network modules. Then, DAVID and Metascape were used for enrichment analysis. After that, in-depth analysis of the proteomics data was carried out to further explore the mechanism of Radix Rhei Et Rhizome intervention in CI. Results. (1) A total of 14 Radix Rhei Et Rhizome potential components and 425 potential targets were obtained. The core components include sennoside A, palmidin A, emodin, toralactone, and so on. The potential targets were combined with 297 CI genes to construct a PPI network. The targets shared by Radix Rhei Et Rhizome and CI include ALB, AKT1, MMP9, IGF1, CASP3, etc. The biological processes that Radix Rhei Et Rhizome may treat CI include platelet degranulation, cell migration, fibrinolysis, platelet activation, hypoxia, angiogenesis, endothelial cell apoptosis, coagulation, and neuronal apoptosis. The signaling pathways include Ras, PI3K-Akt, TNF, FoxO, HIF-1, and Rap1 signaling pathways. (2) Proteomics shows that the top 20 proteins in the differential protein PPI network were Syp, Syn1, Mbp, Gap43, Aif1, Camk2a, Syt1, Calm1, Calb1, Nsf, Nefl, Hspa5, Nefh, Ncam1, Dcx, Unc13a, Mapk1, Syt2, Dnm1, and Cltc. Differential protein enrichment results show that these proteins may be related to synaptic vesicle cycle, vesicle-mediated transport in synapse, presynaptic endocytosis, synaptic vesicle endocytosis, axon guidance, calcium signaling pathway, and so on. Conclusion. This study combined network pharmacology and proteomics to explore the main material basis of Radix Rhei Et Rhizome for the treatment of CI such as sennoside A, palmidin A, emodin, and toralactone. The mechanism may be related to the regulation of biological processes (such as synaptic vesicle cycle, vesicle-mediated transport in synapse, presynaptic endocytosis, and synaptic vesicle endocytosis) and signaling pathways (such as Ras, PI3K-Akt, TNF, FoxO, HIF-1, Rap1, and axon guidance).

2020 ◽  
Author(s):  
Mengying Bao ◽  
Yan Dai ◽  
Xiaojun Chen ◽  
Shijie Liao ◽  
Wenyu Feng ◽  
...  

Abstract Background: As the main active ingredient of Semen Vaccariae, vaccarin is a flavonoid glycoside useful for the prevention and treatment of numerous diseases. Our previous study found that vaccarin can reduce osteolysis-induced titanium by inhibiting osteoclast formation. However, the issue of whether vaccarin can prevent and treat postmenopausal osteoporosis remains unclear.Method: In this study, we explored the mechanism of action of vaccarin for the prevention of postmenopausal osteoporosis via a network pharmacological approach. We identified the intersecting targets of osteoporosis-related genes retrieved from multiple disease target databases, as well as targets of potential action of vaccarin retrieved from drug-related databases. We then used the intersectional targets to establish a protein-protein interaction (PPI) network. Finally, we performed bioinformatics analysis to enrich Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.Results:A total of 28 cross targets of vaccarin and osteoporosis were identified. PPI network analysis identified six target proteins, namely, IL-6, TNF, VEGFA, HSP90AA1, CREB1, and IL-2, which may be the key targets of vaccarin against osteoporosis. The 28 intersectional targets were mainly involved in 23 biological processes, such as regulation of apoptosis, positive regulation of neovascularization, and angiogenesis, whereas KEGG enrichment analysis revealed that they were primarily related to 22 different signaling pathways, such as PI3K/Akt pathway, cancer pathway, hepatitis B pathway, and tuberculosis pathway.Conclusion: We used a network pharmacology approach to predict the key targets of vaccarin for the prevention of osteoporosis from a systems perspective. We determined that the signaling pathways were chiefly engaged in different pathological processes affecting differentiation and apoptosis of bone rebuilding cells, endocrine metabolic disorders, inflammatory responses, and other disease interactions. This study provides a theoretical basis and therapeutic ideas for the treatment of postmenopausal osteoporosis and offers promising directions for further research on the regulatory mechanism of vaccarin.


2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Shiying Zhang ◽  
Zhiying Yuan ◽  
Huaying Wu ◽  
Weiqing Li ◽  
Liang Li ◽  
...  

Objective. To explore the effects of the Hedysarum multijugum Maxim.-Radix Salviae compound (Huangqi-Danshen Compound (HDC)) on oxidative capacity and cardiomyocyte apoptosis in rats with diabetic cardiomyopathy by a network pharmacology-based strategy. Methods. Traditional Chinese Medicine (TCM)@Taiwan, TCM Systems Pharmacology Database and Analysis Platform (TCMSP), TCM Integrated Database (TCMID), and High-Performance Liquid Chromatography (HPLC) technology were used to obtain and screen HDC’s active components, and the PharmMapper database was used to predict HDC human target protein targets. The DCM genes were collected from the GeneCards and OMIM databases, and the network was constructed and analyzed by Cytoscape 3.7.1 and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, HDC was used to intervene in diabetic cardiomyopathy (DCM) model rats, and important biological processes and signaling pathways were verified using techniques such as immunohistochemistry. Results. A total of 176 of HDC’s active components and 442 potential targets were obtained. The results of network analysis show that HDC can regulate DCM-related biological processes (such as negative regulation of the apoptotic process, response to hypoxia, the steroid hormone-mediated signaling pathway, cellular iron ion homeostasis, and positive regulation of phosphatidylinositol 3-kinase signaling) and signaling pathways (such as the HIF-1 signaling pathway, the estrogen signaling pathway, insulin resistance, the PPAR signaling pathway, the VEGF signaling pathway, and the PI3K-Akt signaling pathway). Animal experiments show that HDC can reduce fasting plasma glucose (FPG), HbA1c, and malondialdehyde (MDA) and increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) ( P < 0.05 ). The results of immunohistochemistry showed that HDC can regulate the protein expression of apoptosis-related signaling pathways in DCM rats ( P < 0.05 ). Conclusion. It was initially revealed that HDC improves DCM through its antiapoptotic and anti-inflammatory effects. HDC may play a therapeutic role by improving cardiomyocyte apoptosis in DCM rats.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Zhu ◽  
Bingwu Huang ◽  
Wenbing Jiang

Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.


2021 ◽  
Author(s):  
Cailin xue ◽  
Peng gao ◽  
Xudong zhang ◽  
Xiaohan cui ◽  
Lei jin ◽  
...  

Abstract Background: Abnormal methylation of DNA sequences plays an important role in the development and progression of pancreatic cancer (PC). The purpose of this study was to identify abnormal methylation genes and related signaling pathways in PC by comprehensive bioinformatic analysis of three datasets in the Gene Expression Omnibus (GEO). Methods: Datasets of gene expression microarrays (GSE91035, GSE15471) and gene methylation microarrays (GSE37480) were downloaded from the GEO database. Aberrantly methylated-differentially expressed genes (DEGs) were analysis by GEO2R software. GO and KEGG enrichment analyses of selected genes were performed using DAVID database. A protein–protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. Core module analysis was performed by Mcode in Cytoscape. Hub genes were obtained by CytoHubba app. in Cytoscape software. Results: A total of 267 hypomethylation-high expression genes, which were enriched in biological processes of cell adhesion, biological adhesion and regulation of signaling were obtained. KEGG pathway enrichment showed ECM-receptor interaction, Focal adhesion and PI3K-Akt signaling pathway. The top 5 hub genes of PPI network were EZH2, CCNA2, CDC20, KIF11, UBE2C. As for hypermethylation-low expression genes, 202 genes were identified, which were enriched in biological processes of cellular amino acid biosynthesis process and positive regulation of PI3K activity, etc. The pathways enriched were the pancreatic secretion and biosynthesis of amino acids pathways, etc. The five significant hub genes were DLG3, GPT2, PLCB1, CXCL12 and GNG7. In addition, five genes, including CCNA2, KIF11, UBE2C, PLCB1 and GNG7, significantly associated with patient's prognosis were also identified. Conclusion: Novel genes with abnormal expression were identified, which will help us further understand the molecular mechanism and related signaling pathways of PC, and these aberrant genes could possibly serve as biomarkers for precise diagnosis and treatment of PC.


Author(s):  
Hui Li ◽  
Yongwei Li

Introduction: : Curcuma longa L. has been associated with different antioxidant, anti-inflammatory, bactericidal and anticancer effects, but the mechanisms of the effects are not yet clearly understood. This study aimed to investigate the key targets and the effect of potential molecular mechanisms of Curcuma longa L. extracts on glioma using different network pharmacology analysis approaches. Methods: The components of Curcuma longa were extracted by gas chromatography-mass spectrometry (GC-MS), and the active components related to the occurrence and development of glioma were determined by traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database, and the same targets of the active components and glioma were screened by network pharmacology approach. Then, the protein’s function and regulatory pathway of the common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The protein’s action and regulatory pathway of the common targets were analyzed with the Cytoscape package using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to construct the target interaction network through which the key targets were identified. Results : GC-MS combined with TCMSP database was used to identify the active components related to the occurrence and development of glioma in Curcuma longa. Finally, we identified the active components 1-(1,5-Dimethyl-4-hexenyl)-4-methyl benzene and Zingiberene. At the same time, 190 target genes of Curcuma longa extracts on glioma were obtained using the Venn diagram. The results of GO analysis showed that the biological processes involved included a response to stimulation, metabolic process, inflammatory process, cell differentiation, and regulation of biological processes. KEGG analysis showed that the PI3K-Akt signaling pathway, MAPK signaling pathway, Th17 cell differentiation, and proteoglycan pathway might be involved in cancer. Further analyses showed that the IL-17 signaling pathway and Interleukin-4 and interleukin-13 signaling were involved in the inflammatory pathway. The analysis of key nodes showed that GSK3B, MAPK14, HSP90AA1, MAPK3 and MAPK8 were IL-17 signaling pathways, while HIF1A and JAK3 were Interleukin-4 and interleukin-13 signaling pathways. Conclusion: Curcuma longa extracts can regulate the occurrence and development of glioma by regulating the immune-inflammatory responses.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Kun xia Hu ◽  
Xi Duan ◽  
Li zhu Han ◽  
Hong ye Ju ◽  
Bin Wang ◽  
...  

In this study, allergic rhinitis (AR) disease targets and Xiang Ju tablet-associated targets were determined through the use of databases for the identification of putative therapeutic targets and then combined. After the production of a putative therapeutic target interaction network for Xiang Ju tablets against AR, topological analysis was used to determine the core targets of Xiang Ju tablets in AR treatment. For all putative therapeutic targets, analyses of biological function and pathway enrichment were performed to optimize the biological processes and key signaling pathways of Xiang Ju tablets in AR treatment. The top 5 therapeutic targets of Xiang Ju tablets in AR treatment were identified and included CXCL8, IL1B, IL6, IL10, and TNF. The biological processes, molecular functions, and cell composition related to the use of Xiang Ju tablets in AR treatment were predominantly associated with cytokine production, regulation of protein secretion, and regulation of peptide secretion; cytokine activity, cytokine receptor binding, and receptor ligand activity; and platelet alpha granule lumen, collagen-containing extracellular matrix, and platelet alpha granule. In addition, the top 64 key signaling pathways were identified.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Wenyang Wei ◽  
Wanpeng Lu ◽  
Xiaolong Chen ◽  
Yunfeng Yang ◽  
Mengkai Zheng

Objective. To clarify the therapeutic mechanisms of compound Xuanju capsule-treated rheumatoid arthritis (RA) based on network pharmacology tactics. Method. The TCMSP, TCMID and STITCH databases were used to screen the active ingredients and targets in the compound Xuanju capsule; the OMIM, TTD, PharmGKB and GeneCards databases were applied to screen the RA-related disease targets. Then, the obtained targets were imported into Cytoscape 3.7.1 software to construct the active ingredient-target network and the RA-related disease-target network. The active ingredient-target PPI network, the RA-related disease-target PPI network and the common target PPI network were built by using the STRING platform and Cytoscape 3.7.1 software. The GO and KEGG analyses of the common targets were analyzed by using the Metascape and Bioinformatics online tools. Results. A total of 51 active ingredients and 513 corresponding ingredient targets were harvested from the compound Xuanju capsule; 641 RA-related disease targets were obtained. After two PPI networks were constructed and merged, 116 RA-related targets of compound Xuanju capsules were identified and analyzed. 116 RA-related targets of compound Xuanju capsules are mainly involved in the biological processes and molecular functions, such as the cytokine-mediated signaling pathways, the response to lipopolysaccharide and the blood vascular development, the cytokine activity, the cytokine receptor binding and the receptor regulator activity. Furthermore, 116 RA-related targets of compound Xuanju capsules are concentrated in signaling pathways such as the IL-17, TNF, Th17 cell differentiation, Toll receptor and RA signaling pathway. Conclusion. The compound Xuanju capsule had the action characteristics of multiple components, multiple targets, and multiple pathways in the treatment of RA, which might primarily reduce the release of proinflammatory factors (such as IL-6 and TNF-α) and increase the production of anti-inflammatory factors (such as IL-10) by regulating inflammation-related signaling pathways (such as IL-17), thereby alleviating the inflammatory damage and improving the bone tissue repair.


2020 ◽  
Vol 2020 ◽  
pp. 1-24
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yongmei Shi ◽  
Xiaofei Zhu ◽  
...  

Background. Hedysarum multijugum Maxim.-Chuanxiong rhizoma compound (HCC) is a common herbal formula modified from Buyang Huanwu decoction. Clinical trials have demonstrated its therapeutic potential for ischemic stroke (IS). However, the mechanism of HCC remains unclear. Methods. The HCC’s components were collected from the TCMSP database and TCM@Taiwan database. After that, the HCC’s compound targets were predicted by PharmMapper. The IS-related genes were obtained from GeneCards, and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from the String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis and the Cytoscape 3.7.2 was utilized to construct and analyze the networks. Finally, a series of animal experiments were carried out to validate the prediction results of network pharmacology. The expressions of GRP78, p-PERK, and CHOP proteins and mRNAs in different time periods after HCC intervention were detected by Western blot, immunohistochemistry, and RT-qPCR. Results. A total of 440 potential targets and 388 IS genes were obtained. The results of HCC-IS PPI network analysis showed that HCC may regulate IS-related targets (such as ALB, AKT1, MMP9, IGF1, and CASP3), biological processes (such as endoplasmic reticulum stress, inflammation modules, hypoxia modules, regulation of neuronal apoptosis and proliferation, and angiogenesis), and signaling pathways (such as PI3K-Akt, FoxO, TNF, HIF-1, and Rap1 signaling). The animal experiments showed that HCC can improve the neurobehavioral scores and protect the neurons of IS rats ( P < 0.05 ). HCC inhibited the expression of p-PERK in the PERK pathway from 12 h after surgery, significantly promoted the expression of GRP78 protein, and inhibited the expression of CHOP protein after surgery, especially at 24 h after surgery ( P < 0.05 ). The results of RT-qPCR showed that HCC can significantly reduce the expression of CHOP mRNA in the neurons in the CA1 region of the hippocampus 72 h after MCAO ( P < 0.05 ). Conclusion. HCC may achieve a role in the treatment of IS by intervening in a series of targets, signaling pathways, and biological processes such as inflammation, oxidative stress, endoplasmic reticulum stress, and angiogenesis.


2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Mengxia Yuan ◽  
Qi He ◽  
Zhiyong Long ◽  
Xiaofei Zhu ◽  
Wang Xiang ◽  
...  

Objective. To explore the pharmacological mechanism of Liuwei Dihuang decoction (LDD) for diabetic retinopathy (DR). Methods. The potential targets of LDD were predicted by PharmMapper. GeneCards and other databases were used to collect DR genes. Cytoscape was used to construct and analyze network DR and LDD’s network, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were carried out to verify the results of systematic pharmacology. Results. Five networks were constructed and analyzed: (1) diabetic retinopathy genes’ PPI network; (2) compound-compound target network of LDD; (3) LDD-DR PPI network; (4) compound-known target network of LDD; (5) LDD known target-DR PPI network. Several DR and treatment-related targets, clusters, signaling pathways, and biological processes were found. Animal experiments found that LDD can improve the histopathological changes of the retina. LDD can also increase erythrocyte filtration rate and decrease the platelet adhesion rate ( P < 0.05 ) and decrease MDA and TXB2 ( P < 0.05 ). Compared with the model group, the retinal VEGF and HIF-1α expression in the LDD group decreased significantly ( P < 0.05 ). Conclusion. The therapeutic effect of LDD on DR may be achieved by interfering with the biological processes (such as response to insulin, glucose homeostasis, and regulation of angiogenesis) and signaling pathways (such as insulin, VEGF, HIF-1, and ErbB signaling pathway) related to the development of DR that was found in this research.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Rong Tang ◽  
Xiaoqing Peng ◽  
Yan Wang ◽  
Xiaohong Zhou ◽  
Hong Liu

This study used a network pharmacology approach to investigate the potential active ingredients of Plantaginis Herba and its underlying mechanisms in hyperuricemia treatment. The potential active ingredients of Plantaginis Herba were obtained from TCMSP and ETCM databases, and the potential targets of the active ingredients were predicted using the Swiss TargetPrediction database. The potential therapeutic targets of hyperuricemia were retrieved from the GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. Then, the integrative bioinformatics analyses of candidates were performed by GO analysis, KEGG analysis, and PPI network construction. There were 15 predicted active ingredients in Plantaginis Herba and 41 common targets that may be involved in the treatment of hyperuricemia. A total of 61 GO annotations and 35 signaling pathways were identified by enrichment analysis ( P < 0.01 ). The underlying mechanisms of Plantaginis Herba may be related to insulin resistance, PI3K/AKT, TNF, VEGF, AMPK, and glucagon signaling pathways. Thus, the present study provided potential and promising strategies of Plantaginis Herba for hyperuricemia treatment.


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