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Objective:To explore the possible mechanism of Yangxue Qingnao Granule for the treatment of vascular dementia (VaD) based on network pharmacology and bioinformatics.Methods:The active components and potential targets of Yangxue Qingnao Granule in the treatment of VaD were obtained from TCMSP database, BATMAN-TCM database, GEO database and OMIM database, etc. The heatmap was visualized by using the pheatmap packages in R. Cytoscape 3.8.2 software and the CytoNCA plugin were utilized to build a network of "Chinese materia medica-active component-potential target". CytoNCA plug-in was used to analyze PPI network topology. Metascape was used for GO and KEGG pathway enrichment analyses. Finally, AutoDock Vina 1.5.6 software was applied to construct molecular docking between the active components and potential core targets. Resuls A total of 135 active components of Yangxue Qingnao Granule were screened and 186 potential targets of Yangxue Qingnao Granule against VaD were obtained. GO function enrichment analysis found protein kinase binding, transcription factor binding and other biological functions. KEGG pathway enrichment analysis identified PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, TNF signaling pathway, etc. Molecular docking showed that the main active components of Yangxue Qingnao Granule had good binding activity with the potential targets. Conclusion:Yangxue Qingnao Granule has the characteristics of multi-targets and multi- pathways in the treatment of VaD. It may play a therapeutic role in VaD by inhibiting neuronal apoptosis and reducing inflammatory response.
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Objective:To study the active components and their potential mechanism of Yanghe Decoction for the treatment of chronic osteomyelitis (CO) via the methods of network pharmacology and molecular docking.Methods:Active components and action targets of Yanghe Decoction were screened from TCMSP, BATMAN-TCM and relevant literature. GeneCards, OMIM, DisGeNET, and PharmGKB databases were used to predict the targets for the CO. Cytoscape 3.8.0 software and STRING database were used to build the networks of "Chinese materia medica-active components-potential targets" and "protein-protein interaction", and according to topological parameters in the network, the core active components as well as Hub genes were screened. MCODE plug was used to accomplish clustering analysis of protein modules in PPI network. Then, intersection targets were enriched and analyzed by GO and KEGG in KOBAS database. Finally, molecular docking was carried out with the help of Autodock tool platform to predict the binding ability between the main active components and key targets.Results:A total of 120 active components of Yanghe Decoction and 402 targets were obtained; 1 464 CO-related targets were screened, and there were 103 intersection target genes of Yanghe Decoction-CO, 110 active components related to intersection targets, which mainly contained some flavonoids and Phytosterols, such as quercetin, Kaempferol, and Beta-Sitosterol. There were 9 Hub genes, including TNF, IL6, AKT1, etc., and 4 protein modules which involved the regulation of immune inflammatory response, vascular microcirculation, bone development, and formation, material synthesis and metabolism and other physiological processes. 193 signaling pathways and 1 552 GO results were acquired in KOBAS database. Molecular docking results showed that the active compounds had good binding activity with key targets based on the minimum binding energy of less than - 5 kcal/mol.Conclusion:The mechanism in the treatment of CO with Yanghe Decoction is a complex process of multiple components, multiple targets, and multiple pathways. It mainly regulates targets such as TNF, IL-6, CXCL8, VEGFA, and AKT1 through pathways such as TNF signaling pathway, IL-17 signaling pathway, and Toll-like receptors, participating in local inflammatory reactions, microcirculation, and bone cell metabolism in chronic osteomyelitis, and interfering with the immune escape mechanism of pathogenic bacteria.
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Objective:To explore the active components, targets and mechanism of Guizhi Fuling Pills in the treatment of atherosclerosis (AS) based on network pharmacology and molecular docking technology.Methods:The active components and potential target information of Guizhi Fuling Pills in the treatment of AS was obtained using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SwissTargetPrediction database and Genecards database. The target protein interaction network was constructed by using STRING database. The DAVID database was used to perform the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment on potential targets. AutoDockVina and PyMOL software were used to verify the molecular docking of the main active components and key targets of Guizhi Fuling Pills.Results:A total of 74 active components, 239 potential targets and 4 710 AS-related disease targets were screened, and 182 intersection targets were obtained. A total of 484 biological process items, 132 molecular function items and 74 cellular component items were obtained by GO functional enrichment analysis, and 116 signal pathways were screened by KEGG enrichment analysis. The results of molecular docking suggested that the active components of Guizhi Fuling Pills have good binding activity to the key intersection targets.Conclusion:The active components of Guizhi Fuling Pills, such as sitosterol and paeoniflorin, mainly treat AS by regulating estrogen signal pathway and inflammatory signal pathway through TNF, VEGFA and other targets.
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Objective:To explore the mechanism of Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma medicinal pair in delaying heart aging based on animal experiments, network pharmacology and molecular docking. Methods:Mice were divided into control group, aging group, metformin group and TCM group according to random number table method. All the groups were injected subcutaneously by D-galactose except the control group to build the subacute aging model. Two weeks later, the metformin group was given metformin suspension (150 mg/kg), the TCM group was given Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma lyophilized powder solution (650 mg/kg), and the control group and aging group were given an equivalent volume of ultrapure water by gastric gavage, once a day, six times a week, for 10 weeks. The level of heart TERT mRNA was detected by PCR; the expression of heart p53 was observed by immunohistochemical staining; the morphology of heart tissue was observed by HE staining. TCMSP and SwissTargetPrediciton databases were used to retrieve the active components and targets of Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma medicinal pair; TTD, OMIM, Gene, HAGR, DisGeNET and other data platforms were used to screen the targets of heart aging; after the drug and disease targets were intersected, the active components of them were collected; STRING database, Cytoscape 3.8.0 software, etc. were used to make PPI of the intersection targets, and screen out the key targets; FunRich was used to perform enrichment analysis of cellular components, molecular functions, biological processes, and biological signal pathways for key targets; Schr?dinger Maestro software was used to do the molecular docking of the screened active components and key targets, and docking results were visualized via PyMOL 2.1 software. Results:Experiment results showed that Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma could significantly ameliorate the damage of aging heart tissues, elevate TERT mRNA level, while significantly reducing the positive expression of p53. A total of 32 active components from the medicinal pair were screened, corresponding to 637 target genes. There were 263 targets for heart aging, and 67 intersection targets of drug active component targets and heart aging targets. 31 key targets were obtained after screening. Enrichment analysis showed that molecular functions were related to transcription factor activity and protein-tyrosine kinase activity. Biological processes involved signal transduction and cell communication. Signaling pathways mainly involved PDGFR-beta, PI3K-Akt, S1P1, Glypican, TRAIL, and Glypican 1. The molecular docking results showed that kaempferol, suchilactone, and ginsenoside Rg5_qt in the medicinal pair had a strong binding ability to p53. Conclusion:Ginseng Radix et Rhizoma- Notoginseng Radix et Rhizoma- Chuanxiong Rhizoma may achieve the effect of delaying heart aging by inhibiting p53 expression, providing a foundation for further research on mechanism of invigorating qi and activating blood circulation drugs to delay heart aging.
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Objective:To analyze the molecular mechanism of Zhenqi Fuzheng Capsules in the adjuvant treatment of AIDS by network pharmacology method and molecular docking technology.Methods:The active components and targets of Zhenqi Fuzheng Capsules were obtained through TCMSP, and the AIDS-related targets were obtained through GeneCards, OMIM and DrugBank databases. The intersection target PPI network was constructed through STRING 11.5 database, and Cytoscape 3.9.1 software was used for network topology analysis; Metascape database was used for GO function and KEGG pathway enrichment analysis of core targets; Cytoscape 3.9.1 was used to construct Zhenqi Fuzheng Capsules component-target-pathway network; Autodock Tools software was used to carry out molecular docking of core targets and active components.Results:Totally 31 active components and 180 targets of Zhenqi Fuzheng Capsules were screened out. TNF, IL6, AKT1, IL1B, TP53, VEGFA, RELA, EGFR and CASP3 were identified as the core targets. GO functional enrichment analysis obtained 1 436 biological processes, 53 cellular components, and 117 molecular functions. KEGG pathway enrichment analysis obtained 167 pathways, which were related to pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, and IL-17 signaling pathway was closely related. Molecular docking results showed that core targets such as AKT1 and TNF had good binding activity to quercetin, kaempferol, and luteolin.Conclusion:The main active components of Zhenqi Fuzheng Capsules in the adjuvant treatment of AIDS are quercetin, kaempferol and luteolin, which may treat AIDS through the IL-17 signaling pathway.
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Objective:The mechanism of Indigo Naturalis in the treatment of ulcerative colitis (UC) was predicted by GEO chip combined with network pharmacology, and preliminarily verified by molecular docking. Methods:The main active components and targets of Indigo Naturalis were obtained by searching TCMSP, SymMap database, SwissTargetPrediction and Pharmmapper. The UC disease targets were obtained from DrugBank database, OMIM database, TTD database, Disgenet database and GEO gene chips. Venn diagram was used to show drug-disease common targets. The protein-protein interaction (PPI) network of intersection targets was analyzed by String platform, and Cytoscape 3.8.2 software was used to construct the PPI network of components and disease targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the core targets. AutoDock Vina 1.2.1 was used for molecular docking, and the results were visualized by Discovery studio Visualizer. Results:A total of 10 active components and 184 compound targets of IN-UC, of which 42 were core targets, were enriched and analyzed by GO and KEGG. The therapeutic effect of Indigo Naturalis on UC may involve activation of various process, such as reactive oxygen species metabolism, heme binding, protein phosphatase binding, secretory granule exocytosis, cytoplasmic vesicles, cell focal adhesion and cell substrate connection, and regulates PI3K/Akt signal pathway, human cytomegalovirus infection signal pathway, EB virus infection signal pathway HF1 signaling pathway and insulin resistance signaling pathway to treat UC. Conlusion:Indigo Naturalis has the characteristics of multi-component, multi target and multi pathway in the treatment of ulcerative colitis. Through PTGS2, CAT and other core targets, it can regulate PI3K/Akt signal pathway, human giant cell signal pathway, HIF-1 signal pathway to play a therapeutic role.
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Objective:To predict the mechanism of Danggui Buxue Decoction for anti-myocardial ischemia-reperfusion injury and "treating different diseases with the same method" in ischemic stroke based on network pharmacology and molecular docking.Methods:The active components and targets of Danggui Buxue Decoction were screened by retrieving the database of TCMSP and literature; the corresponding targets of myocardial ischemia-reperfusion injury and ischemic stroke were found by OMIM and GeneCards database; the intersection targets of Danggui Buxue Decoction and disease were obtained by using Venny diagram, and the common target network and protein-protein interaction network were constructed by Cytoscape 3.7.1 software and STRING database. The GO and KEGG pathways were enriched by David Database, and the Bio GPS database was used to obtain the tissue distribution information of the key targets. The molecular docking technology was used to verify the results.Results:There were 21 active components in Danggui Buxue Decoction, 181 effective targets and 93 cross targets with diseases. The key components were quercetin, Kaempferol, β-sitosterol, formononetin and isorhamnetin. The key targets were AKT1, TNF, IL6, IL-1β and VEGFA. The enrichment results showed that the main action pathways were fluid shear force and arteriosclerosis, lipid and arteriosclerosis, AGE-RAGE signal pathway in diabetic complications, and the core targets were mainly located in the medullary cells, dendritic cell, smooth muscle, prostate, thyroid and other tissues. The results of molecular docking showed that quercetin had the best binding effect to IL-1β, while isorhamnetin had the best binding effect to IL-1β.Conclusion:Danggui Buxue Decoction is against myocardial ischemia-reperfusion injury and ischemic stroke through hemodynamics, lipid metabolism, inflammatory reaction, oxidative stress, immune reaction and cell apoptosis, plays the role of "treating different diseases with the same method".
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Objective:To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods:The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened. The GeneCards, OMIM, TTD, DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. The Cytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-disease network diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-in was used to screen core active components and targets. The bioenrichment analysis of GO and KEGG was carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram was drawn, and the core active components and core targets were docked in PyMOL and AutoDockTools 1.5.7.Results:A total of 102 potentially active components and 62 intersection targets were obtained, and 8 active components and 7 core targets were screened. Enrichment analysis showed that the key targets were mainly enriched through the signaling pathways of fluid shear stress and atherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biological processes such as the response to nutritional levels and the regulation of small molecule metabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion:The main active components of Linggui Zhugan Decoction are quercetin, kaempferol and naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid and atherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.
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Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.
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Objective:To screen the main active components of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression; To predict the key targets and signaling pathways; To establish a multi-level network structure and comprehensively reveal the synergistic mechanism of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression.Methods:Main components of Danggui Buxue Decoction were searched in TCMSP detabase, combined with literature reports to supplement and improve information. The protein targets of compounds were standardized in the UniProt protein database. Myelosuppression targets were obtained by querying TTD database, GeneCards database, DrugBank detabase and OMIM database. The effective components and common targets of Danggui Buxue Decoction were screened, and the protein-protein interaction (PPI) network of intersection targets was analyzed by String platform to construct the PPI network of effective components and disease targets. Gene ontology (GO) analysis and enrichment pathway analysis of Kyoto gene and genome encyclopedia (KEGG) of key target proteins were conducted through Metascape data platform. Both the results of GO and KEGG analysis were presented. AutoDock software was used for molecular docking to explore the interaction between core targets and active components, and the results were imported into PyMOL software for visual analysis.Results:Danggui Buxue Decoction has a total of 22 active components of Chinese materia medica for improving chemotherapy-induced myelosuppression, 294 potential targets, 3 301 disease targets, and 210 common targets of Chinese materia medica and diseases. Core targets were obtained through network topology analysis and molecular docking. The first five were ESR1, MAPK1, RELA, AKT1, PIK3R1; GO enrichment results obtained 2 430 biological processes, 125 cellular components and 217 molecular functions, including responses to inorganic substances, membrane rafts, micro-organisms membrane region, transcription factor binding, etc.; KEGG enriched 385 pathways, of which cancer pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, etc. were the main signaling pathways; molecular docking results showed that β-sitosterol has the best binding performance with HSP90AA1, formononetin and RELA in astragalus when it was in Angelicae Sinensis Radix.Conclusion:Danggui Buxue Decoction regulates ESR1, MAPK1, RELA, AKT1 and other core targets through various active components such as quercetin, formononetin, and β-sitosterol. PI3K-AKT and other related signaling pathways can improve chemotherapy-induced myelosuppression and provide a basis for its clinical application.
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Objective:To analyze the mechanism of Kaixin San in treating Alzheimer disease (AD) based on the TCM integrated pharmacology platform combined with GEO chip differential gene analysis method.Methods:By searching TCMIP and Drugbank database, the active components and related molecular targets of Kaixin San were obtained. GSE4757 chip data was obtained through GEO database, and its differential genes were obtained using R language to draw heat map and volcano map. Molecular target map of differentially expressed genes between Kaixin San and AD was constructed through Cytoscape 3.7.2. Bisogenet and CytoNCA were used to draw the target topological network, and GO enrichment analysis and KEGG enrichment analysis of Kaixin San and AD gene were carried out.Results:86 active components of Kaixin San were obtained to treat AD, and 29 differential genes shared with GEO were obtained. PPI topological network was constructed. 6 core candidate genes were screened, and were merged with KEGG pathway enriched genes to obtain important genes for disease treatment, such as CHRM1, CHRM2, ACHE, CHRM3, CASP8, PTGS2, DRD1, CACN1S, ADRB1. 375 GO entries were obtained, mainly involving biological processes such as vasoconstriction, postsynaptic membrane plasticity, neurotransmitter transmission, etc. KEGG enrichment analysis mainly involved cholinergic synaptic signal pathway, cAMP signal pathway, calcium signal pathway, nerve ligand receptor interaction signal pathway, etc.Conclusions:Kaixin San shows the features of multi-component, multi-target and multi-channel in treating AD. It can play a role in the treatment of AD by inhibiting inflammatory reaction, reducing the activity of acetylcholinesterase and regulating the concentration of calciumion.
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Objective:To explore the mechanism of Shuerjing Capsule in treating primary dysmenorrhea based on molecular docking of network pharmacology and in vivo experiment.Methods:By using TCMSP to screen the active components and targets of Shuerjing Capsule; by using GeneCards and DrungBank databases to retrieve targeted proteins of primary dysmenorrhea, and the intersection targets of drugs and diseases were obtained through Weishengxin online platform; by using Cytoscape 3.9.1 software to produce component-target network of Shuerjing Capsule for the treatment of primary dysmenorrhea; by STRING databases to construct drug-disease target PPI network; by DAVID database to perform GO and KEGG pathway enrichment analysis.The key active components of the drug and the core targets of the disease were obtained with molecular docking. The rats were randomly divided into control group, model group, the low-dose group, medium-dose group and high-dose group of Shujing Capsule (0.15, 0.21, 0.42 g/kg), and ibuprofen group (20 mg/kg), with 10 rats in each group. The animal model of primary dysmenorrhea was established by subcutaneous injection of estradiol benzoate and intervented by drugs. The number of writhing reaction, uterine contractile inhibition rate and uterine index of rats were observed. The expressions of TNF-α, IL-6 and IL-1 in serum and the levels of PTGS2 and VEGFA in uterine tissue were detected by ELISA.Results:A total of 188 active ingredients of Shuerjing Capsule were screened, and 51 targets of Shuerjing Capsule and primary dysmenorrhea were identified. TNF, IL-6, AKT1 and TP53 may be the key targets of Shuerjing Capsule in the treatment of primary dysmenorrhea. A total of 519 GO biological processes and 119 related signaling pathways were obtained, among which estrogen, IL-17, HIF-1 and other signaling pathways were closely related to the treatment of primary dysmenorrhea. The results of molecular docking were good, among which stigmasterol had the strongest binding ability to TP53. The experimental results showed that compared with the model group, the uterine index and the number of torsion were decreased in the low -, medium - and high-dose Shuojing Capsule groups ( P<0.05), the uterine contraction inhibition rate increased ( P<0.05); Serum levels of TNF-α, IL-6 and IL-1 of medium and high dose group decreased ( P<0.05), the levels of PTGS2 and VEGFA in uterine tissues decreased ( P<0.05). Conclusion:Shuerjing Capsule has the effect of anti-inflammatation and improveing hypoxia, which may be related to the inhibition of TNF-α, IL-6 and IL-1 inflammatory factors in serum and the expression of PTGS2 and VEGFA proteins in uterine tissues.
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Objective:To explore the mechanism of Fuyuan Xingnao Decoction in treatment of cerebral infarction based on network pharmacology and molecular docking.Methods:The active components and action targets of Fuyuan Xingnao Decoction were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),Traditional Chinese Medicine Integrated Database (TCMID),Bioactivity data of small organic molecules (PubChem),Universal Protein (Uniprot) and Swiss Target Prediction database platform. The databases of GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and Drug Bank and Pharmacogenomics Knowledgebase (PharmGKB) were used to screen targets of cerebral infarction. The drug target genes in Fuyuan Xingnao Decoction were intersected with those of cerebral infarction, the intersecting targets were introduced into Cytoscape 3.8.2 software to construct the component target network, and the PPI protein interaction network was constructed by using STRING analysis platform and Cytoscape 3.8.2 software to screen the core targets. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) function enrichment analysis were carried out on the common target genes of Fuyuan Xingnao Decoction and cerebral infarction disease to obtain the relevant signal pathways. Finally, AutoDock and Pymol software were used for molecular docking between the predicted target and its corresponding components.Results:After screening, 80 effective components of Fuyuan Xingnao Decoction for treatment of cerebral infarction and 214 common targets of Fuyuan Xingnao Decoction and cerebral infarction were obtained. The core targets such as MAPK1, RELA, TP53, JUN, AKT1 and HSP90AA1 were related to the key targets of cerebral infarction, and they participated in the biological process of regulating the response to drugs, lipopolysaccharide and oxygen level, etc. The cell composition involved membrane raft, membrane micro region and nerve cell body, etc. Molecular functions mainly focused on nuclear receptor activity, ligand activated transcription factor activity, DNA binding transcription factor binding, etc.; it also involved in signal pathway of lipid and atherosclerosis, chemical carcinogen and receptor activation, fluid shear stress and atherosclerosis, etc. Molecular docking showed that good binding activities were seen between Quercetin and HSP90AA1 (-9.4 kJ/mol), between Kaempferol and HSP90AA1 (-9.4 kJ/mol), between Isorhamnetin and HSP90AA1 (-9.1 kJ/mol), and between Quercetin and JUN (-8.6 kJ/mol).Conclusion:Fuyuan Xingnao Decoction can prevent and treat cerebral infarction by regulating vascular endothelial function, promoting blood circulation, repairing and improving neural function, protecting blood-brain barrier, reducing cell apoptosis, and regulating immune and inflammatory response.
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Objective:To explore the molecular mechanism of Danggui Niantong Decoction in the treatment of gouty arthritis (GA) based on network pharmacology and molecular docking.Methods:By selecting for the active components and targets of Danggui Niantong Decoction with TCMSP, and retrieving the GeneCards, OMIM, PharmGKB and DrugBank databases to obtain GA related targets. The potential targets of Danggui Niantong Decoction in the treatment of GA were obtained by the intersection of mappings. The regulation network of Chinese medicine compound and protein-protein interaction network of Danggui Niantong Decoction were constructed by Cytoscape software, and the targets of Danggui Niantong Decoction in the treatment of GA were analyzed by GO and KEGG enrichment by David Database. Finally, molecular docking was performed by using Autodock software.Results:There are 198 active components that could treat GA in Danggui Niantong Decoction. The key active components are Quercetin and Kaempferol. There are 46 key targets, the core targets are NFE2L2, HMOX1, PPARA, PTGS2, IL1β, CXCL8. GO enrichment suggests that the key genes are primarily involved in many biological processes such as Inflammatory response regulation, response to oxidative stress, Fatty acid metabolism process, steroid metabolism, lipopolysaccharide response and reactive oxygen species metabolism. KEGG pathway indicates that Danggui Niantong Decoction mainly acted on IL-17 signal pathway, HIF-1 signal pathway, TNF signal pathway and AGE-RAGE signal pathway. Molecular docking shows that the active components of Danggui Niantong Decoction and action target of GA can combine toghether with high efficiency, and the structure is stable.Conclusion:Danggui Niantong Decoction has multi-component, multi pathway and multi-protein characteristics. Danggui Niantong Decoction can treat GA by regulating immune inflammatory reaction and oxidative stress reaction.
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The last essential enzyme in the biosynthetic pathway of trilobatin, phloretin-4'-O glycosyltransferase (P4'-OGT), catalyzes the conversion of trilobatin to phloretin in vitro. However, only a few P4'-OGTs have been found in plants. This study used Malus domestica phloretin-4'-O glycosyltransferase (MdPh-4'-OGT) as a query to identify and clone two UDP-glucuronosyltransferase (UGT) genes, designated UGT74L2 and UGT74L3, from the transcriptome of Andrographis paniculata. According to a phylogenetic tree analysis, UGT74L2 and UGT74L3 belonged to the UGT74 family, which has been linked to several activities in other species. The in vitro enzymatic reaction demonstrated that UGT74L2 could particularly catalyze the formation of trilobatin from phloretin, but UGT74L3 had no effects. By using Ni-NTA affinity chromatography to extract the soluble UGT74L2 recombinant protein, the enzymatic kinetics of the activity was investigated using phloretin as the substrate. The results showed that the optimal temperature and pH for UGT74L2 enzymatic reaction were 40 ℃ and 8.0 (Tris-HCl system), respectively. Three metal ions (Ca2+, Mn2+ and Co2+) showed inhibitory effect on the activity of UGT74L2, while Mg2+ could improve the activity of UGT74L2. Other tested metal ions have no significant effect on UGT74L2. The results of enzymatic kinetic parameters that the Km value was 29.84 μmol·L-1, the kcat was 0.02 s-1, and the kcat·Km-1 was 572.6 mol-1·s-1. By homology modeling, molecular docking and mutation experiments, we found that multiple amino acids residues around the substrate binding pocket play quite an important role during catalytic process, In summary, we identified a novel P4'-OGT gene from medicinal plant Andrographis paniculata and provided a new efficient catalyst to synthesize trilobatin. Meanwhile, this study provides a reference for mining new efficient glycosylation modules from plants.
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Objective:To explore the key targets of ginkgo leaves extract against diabetic retinopathy (DR), and the underlying pharmacological mechanism by network pharmacology.Methods:Potential targets of active components in ginkgo folium were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Swiss Target Prediction database.Therapeutic targets highly related to DR were retrieved from the GeneCards and DisGENET databases.The intersection targets were subjected to Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to construct the active components-targets network.Based on the degree of network nodes, key active components and key targets were obtained for molecular docking verification.Results:A total of 27 active components and 34 potential therapeutic targets of ginkgo leaves extract in the treatment of DR were screened out.GO enrichment analysis indicated that these therapeutic targets were mainly enriched in the processes of inflammation, oxidative stress, angiogenesis and hypoxic damage.KEGG pathway enrichment analysis revealed that the advanced glycation end product-receptor for advanced glycation end product, mitogen active protein kinase, phosphatidylinositol-3-kinase-protein kinase B, hypoxia inducible factor-1, tumor necrosis factor (TNF) and interleukin (IL)-17 signaling pathways were mainly enriched.According to degree value calculated from the active components-targets network, the top 4 key active components with higher degrees were quercetin, kaempferol, luteolin and isorhamnetin, and the top 8 key targets were serine/threonine protein kinase 1, vascular endothelial growth factor A, IL-6, TNF, nitric oxide synthase 3, peroxisome proliferator activated receptor-γ, IL-10 and matrix metalloproteinase-9.The binding activity between key active components and key targets was good.Conclusions:A variety of active compounds contained in ginkgo leaves extract can target various therapeutic targets related to DR, and regulate multiple signal pathways, thereby exerting a therapeutic effect on DR.
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Objective:Based on network pharmacology and molecular docking to explore the targets and mechanism of Xiaoyong Sanjie Formula treating Non-Puerperal Mastitis (NPM).Methods:By retrieving the active components and the corresponding target information of each component in Xiaoyong Sanjie Formula with Pharmacology Database and Analysis Platform of Chinese Medicine System (TCMSP), and NPM-related genes in database like GeneCard, OMIM, PharmGkb, TTD, and DrugBank, the data of the core targets of Xiaoyong Sanjie Formula and disease-related genes was compared to obtain intersecting genes, and the STRING database was used to analyze the protein interaction network and find the core genes. With the help of Cytoscape 3.8.0, the active ingredient-target-pathway regulation network diagram of Xiaoyong Sanjie Formula for the treatment of NPM was established. The R language pack was used to enrich the targets with GO function and KEGG pathway enrichment, and the potential targets and mechanism of Xiaoyong Sanjie Formula in the treatment of NPM were explored. Finally, molecular docking verification was carried out to analyze the effecacy of key components and potential core targets of Xiaoyong Sanjie Formula.Results:Network pharmacological analysis showed that there were 47 active component and 1 692 NPM-related potential targets in Xiaoyong Sanjie Formula, and 235 core targets of NPM in the treatment of Xiaoyong Sanjie Formula. The key components of Xiaoyong Sanjie Formula in the treatment of NPM include Quercetin, Naringenin, Kaempferol, Diosgenin, Luteolin, etc., with the core targets of intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGFA), tumor necrosis factor (TNF), interleukin-6 (IL-6), Epidermal growth factor receptor (EGFR), interleukin-1β (IL-1B), chemokine-8 (CXCL8), chemokine-2 (CCL2), etc. GO enrichment obtained 1 492 biological process entries. The KEGG pathway is enriched to obtain 105 pathways, including the TNF signaling pathway, the PI3K-Akt signaling pathway, the NF-kappa B signaling pathway, and the JAK-STAT signaling pathway, IL-17 signaling pathway, C-type lectin receptor signaling pathway, etc. The final molecular docking verified that the key active ingredients of Xiaoyong Sanjie Formula could bind with the potential core targets closely.Conclusion:Xiaoyong Sanjie Formula can treat NPM with multi-component, multi-target characteristics,which plays a role of treating NPM through signaling pathways such as immuno-inflammatory response, the metabolism of the medicine, cellular adaptive stress response, and vascular function regulation.
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Objective:To explore the mechanism of the active compounds in Banxia Houpo Decoction treating tension type headache through network pharmacology and molecular docking.Methods:The potentially effective components and targets of Banxia Houpo Decoction were screened by TCMSP, and the action targets of tension type headache were obtained by GeneCards, PharmGKB, TTD, Drugbank and OMIM. The intersection target of "Banxia Houpo Decoction - tension type headache" was obtained by Perl software. The protein interaction network was uploaded to STRING database and topological analysis was carried out. With the help of Cytoscape 3.8.0 software, the visualization network of "Banxia Houpo Decoction - medicine ingredient-Target-tension type headache" was constructed, and the GO enrichment analysis and KEGG pathway enrichment analysis of the intersection targets were carried out by using R 4.1.0 language and related programs. The AutoDockTools-1.5.6 software was used to complete the molecular docking analysis.Results:There were 33 intersection targets in Banxia Houpo Decoction and tension type headache. Topological attribute analysis suggested that MAPK1, TP53, ESR1, PTGS2, MYC, CYP1A2, CYP3A4 and GSTP1 might be important potential targets of Banxia Houpo Decoction in the prevention and treatment of tension type headache. GO enrichment analysis showed 516 cell biological processes (BP), 62 cell components (CC) and 149 molecular functions (MF). KEGG pathway enrichment analysis showed that there were 94 related signal pathways, such as cGMP-PKG signaling pathway, Cholinergicsynapse, Serotonergic synapse and TNF signaling pathway.Conclusions:Banxia Houpo Decoction has multi-component, multi-target and multi-pathway characteristics in the prevention and treatment of tension-type headache. It mainly acts on 5-HT synaptic pathway, TNF signal pathway, cholinergic synaptic pathway, G protein coupled receptor pathway and other pathways through ESR1, TP53, PGTS2 and other multi target.
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Objective:To explore the ingredients, targets, and mechanisms of Hanchuan Zupa Granules in the treatiment of Influenza A virus.Methods:By using Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP), GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGkb), Therapeutic target database (TTD) and DrugBank database to obtain relevant components and targets of Hanchuan Zupa Granules in the treatment of Influenza A virus; R software was used for the obtain of Hanchuan Zupa Granules -Influenza A virus intersection targets; Cytoscape software was applied for the construction of "Hanchuan Zupa Granules-component-target" network; Protein-protein interaction network (PPI) and topological analysis were constructed by STRING database and Cytoscape software. Intersection targets for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by R software; Auto Dock Tools were used for molecular docking.Results:All together 111 potential active ingredients, with corresponding 131 targetswere identified from Hanchuan Zupa Granules in the treatment of Influenza A virus. Quercetin, apigenin, luteolin, kaempferol, wogonin, etc. are included as core ingredients. STAT3, MAPK1, MAPK3, AKT1, JUN, etc. are included as core targets. Intersection targets were mainly enriched in 178 signal pathways such as IL-17 signal pathway, influenza A signal pathway, TNF signal pathway, etc; Molecular docking showed that core component had a good affinity with the target.Conclusion:Hanchuan Zupa Granules could play the role of anti-Influenza A virus with multi-component-multi-target-multi-pathway,characteristics, and this syudy provide a basis for future experimental research on its mechanism.
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Objective:To discuss the mechanism of Yueju Pill in the treatment of functional dyspepsia (FD) based on network pharmacology and molecular docking.Methods:The chemical components and action targets of Yueju Pill were screened out by TCMSP platform and HERB, BATMAN-TCM database combined with literature were used to supplement effective components of Vietnam bow. The targets of FD were screened out by GeneCards database and OMIM database, and the intersection of the two targets was used to analyze the protein interactions using the STRING platform to construct the PPI network. Metascape platform was used for GO and KEGG pathway enrichment analysis, and Cytoscape 3.7.2 software was used to construct a network of "Yueju Pill components-functional dyspepsia targets-pathways". Online mapping tools were used to obtain the Venn plot of the intersection targets of Yueju Pill, FD and its related pathogenesis. Finally, AutoDock software was used for molecular docking.Results:The main active components of Yueju Pill in the treatment of FD are quercetin, wogonin, luteolin, kaempferol, etc. The main targets are AKT1, MAPK1, JUN, RELA, IL6, BCL2, BAX, MAPK8, EGFR, ESR1, etc. Molecular docking shows that the targets and the active components of the Yueju Pill have better binding abilit. The GO enrichment analysis result shows that there are 2 273 biological processes, 152 molecular functions and 91 cell components. KEGG enrichment analysis shows that there are 344 pathways associated with FD. According to literature review, the pathways related to FD include PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway, etc.Conclusion:Yueju Pill might act on AKT1, MAPK1, JUN, RELA, IL6, BCL2, BAX, MAPK8, EGFR, ESR1 and other targets to regulate PI3K-Akt signaling pathway, AGE-RAGE signaling pathways and IL-17 signaling pathway and it could treat FD.