Molecular targets and mechanisms of Jiawei Jiaotai Pill on diabetic cardiomyopathy based on network pharmacology

BACKGROUND Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis,increase insulin secretion,and improve blood glucose tolerance.However,its mechanism of action in the treatment of diabetic cardiomyopathy(DCM)remains unclear,hindering research efforts aimed at developing drugs specifically for the treatment of DCM.AIM To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment.METHODS We explored various databases and software,including the Traditional Chinese Medicine Systems Pharmacology Database,Uniport,PubChem,GenCards,String,and Cytoscape,to identify the active components and targets of Jiawei Jiaotai Pill,and the disease targets in DCM.Protein-protein interaction network,gene ontology,and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM.Molecular docking of key active components and core targets was verified using AutoDock software.RESULTS Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified.There were 100 common targets between the DCM and Jiawei Jiaotai Pills.Through this screening process,TNF,IL6,TP53,EGFR,INS,and other important targets were identified.These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase(MAPK)MAPK cascade,response to xenobiotic stimuli,response to hypoxia,positive regulation of gene expression,positive regulation of cell proliferation,negative regulation of the apoptotic process,and other biological processes.It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications,DCM,PI3K-Akt,interleukin-17,and MAPK signaling pathways.Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target.CONCLUSION The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress,cardiomyocyte apoptosis and fibrosis,and maintaining metabolic homeostasis.

Exploring the mechanism of action of Wuzhuyu Decoction for vascular headache based on network pharmacology and molecular docking

Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.

Exploring the targets and molecular mechanism of glycyrrhetinic acid against diabetic nephropathy based on network pharmacology and molecular docking

BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health burden.AIM To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid(GA)treats DN,subsequently validating these predictions through experimental means.METHODS The study initially identified GA targets using Pharm Mapper and the TCMSP database.Targets relevant to DN were obtained from the Genecards,OMIM,and TTD databases.The Venny database facilitated the acquisition of intersecting targets between GA and DN.The String database was used to construct a protein interaction network,while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)analysis.Molecular docking experiments were performed using Autodock software with selected proteins.Experimental validation was conducted using renal proximal tubular cells(HK-2)as the study subjects.A hyperglycemic environment was simulated using glucose solution,and the effect of GA on cell viability was assessed through the cell counting kit-8 method.Flow cytometry was employed to detect cell cycle and apoptosis,and protein immunoblot(western blot)was used to measure the expression of proteins of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and insulin resistance pathway,including insulin receptor(INSR),PI3K,p-PI3K,AKT,p-AKT,and glycogen synthase kinase-3(GSK3).RESULTS A total of 186 intersecting targets between GA and DN were identified,which were associated with 144 KEGGrelated enrichment pathways,375 GO biological process entries,45 GO cellular component entries,and 112 GO cellular function entries.Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase(MAPK)-1,SRC,PIK3R1,HSP90AA1,CASPASE9,HARS,KRAS,and MAPK14.In vitro experiments revealed that GA inhibited HK-2 cell viability,induced cell cycle arrest at the G2/M phase,and reduced apoptosis with increasing drug concentration.Western blot analysis showed that GA differentially up-regulated GSK3 protein expression,up-regulated AKT/p-AKT expression,down-regulated INSR,AKT,p-AKT,PI3K,and p-PI3K protein expression,and reduced p-PI3K/PI3K levels under high glucose conditions.CONCLUSION GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway,thereby inhibiting HK-2 cell viability,reducing HK-2 cell apoptosis,and inducing cell cycle arrest at the G0/G1 phase.

Based on network pharmacology and molecular docking technology to explore the mechanism of Panax notoginseng in the treatment of membranous nephropathy

Objective:Based on network pharmacology and molecular docking technology to explore the mechanism of Professor Cao Enze's application of Panax notoginseng in the treatment of membranous nephropathy.Methods:TCMSP database was used to obtain the effective components and corresponding target information of Panax notoginseng,and Gene Cards database was used to obtain the disease target genes of membranous nephropathy.The intersection targets of the two were taken and the Venn diagram was drawn.The STRING database was used to obtain the protein interaction relationship,and the PPI network diagram was constructed by Cytoscape 3.9.1 software to screen out the core targets of Panax notoginseng in the treatment of membranous nephropathy.GO function and KEGG pathway enrichment analysis were performed using the David database to obtain the potential pathway of Panax notoginseng in the treatment of membranous nephropathy.Finally,Autodock software was used to verify the molecular docking of the main active components of the drug with the core targets.Results:A total of 7 effective components such as quercetin,ginsenoside rh2,Mandenol and Stigmasterol were retrieved,and 127 potential targets of Panax notoginseng in the treatment of membranous nephropathy were screened out.By PPI network topology analysis,23 core targets such as JUN,TP53,RELA,AKT1 and MAPK1 were screened out.GO functional enrichment analysis contained 703 biological processes,55 cell components and 121 molecular functions,and KEGG signal pathway enrichment analysis enriched 171 signal pathways.The results of molecular docking showed that there was a strong binding ability between the main core targets and the main components of Panax notoginseng.Conclusion:Through network pharmacology,it is concluded that Panax notoginseng treats membranous nephropathy through multiple targets and multiple pathways,which provides a theoretical basis for subsequent basic research.

Research Progress on the Antineoplastic Pharmacological Effects and Mechanisms of Litchi Seeds

Researchers have proven the Litchi seeds of possessing salutary pharmacodynamic effects, such as dispelling cold, relieving pain, promoting the circulation of qi, and removing stasis. This has resulted in its categorization as an affinal drug and diet in the traditional Chinese medicine. Important research progress has been obtained on the chemical components, traditional pharmacological effects, antivirus and antitumor effects, their molecular mechanisms and immune effects of litchi seeds in recent years. In this review, we have focused on the antitumorrelated effects and mechanisms for the purpose of better utilization and comprehensive understanding of litchi seeds.

Study on the mechanism of Wuzi Yanzong pill in treating osteoporosis based on network pharmacology and molecular docking

Background:Based on network pharmacology and molecular docking,our study discussed the mechanism of Wuzi Yanzong pill in treating Osteoporosis(OP),which lays the foundation for drug development of OP.Methods:The chemical compounds and potential targets of Wuzi Yanzong pill were explored through TCMSP,PubChem,Swiss ADME and other databases.GeneCards,OMIM and Drugbank databases were used to obtain OP related targets.The intersection between the targets of Wuzi Yanzong pill and the related targets of OP was found by drawing a Venn diagram.PPI network was constructed with the STRING database and core targets were screened.The TCM-compound-action target-disease network was drawn using the Cytoscape software.The Metascape platform was used to find the pathways and functions for core target enrichment.Molecular docking validation of action compounds and core targets is completed by software such as Auto Dock Vina.Results:59 compounds and 707 action targets of Wuzi Yanzong pill were found.603 disease targets were selected,106 intersection targets were found using a Venn diagram,and 37 core targets were screened.By enrichment analysis,143 KEGG pathways,1026 GO biological processes,23 GO cell compositions and 60 GO molecular functions were obtained.The results of molecular docking showed that the effective compounds of Wuzi Yanzong pill,such as stigmasterol,quercetin,kaempferol andβ-sitosterol,had high binding activity with STAT3,TNF and IL6 core target proteins.Conclusion:Wuzi Yanzong Pill may play a role in treating OP by regulating STAT3,TNF,IL-6,TP53,VEGFA,JUN,AKT1,IL-1B,SRC,MMP9 and other pathways,as well as cancer-correlation,rheumatoid arthritis-correlation,MAPK,Th17 cell differentiation,IL-17,TNF signaling pathway and so on,to interpret Wuzi Yanzong pill’s clinic.

Exploring Action Mechanism of Sanzi Yangqin Decoction in Treating Bronchial Asthma Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the molecular mechanism of Sanzi Yangqin Decoction in the treatment of bronchial asthma based on network pharmacology and molecular docking.[Methods]The components of Fructus Perillae,Semen Raphani and Semen Sinapis three traditional Chinese medicine-related components and targets of Feiduqing Sanzi Yangqin Decoction were obtained using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the targets of bronchial asthma were obtained using Genecards and OMIM databases.Sanzi Yangqin Decoction"drug-active ingredient-target-disease"network was established with the aid of Cytoscape 3.7.2 software and network topology analysis was carried out.The gene ontology(GO)function enrichment analysis and the KEGG pathway enrichment analysis were performed by DAVID.The top 3 components and targets in the network topology analysis were respectively molecularly docked.[Results]Through network analysis,4 key active components were obtained,mainly luteolin,arachidonic acid,β-carotene,etc.;5 key targets,mainly NCOA2,PGR,PTGS2,etc.Through GO analysis,523 items(P<0.05)were obtained,including 396 items in biological process(BP),53 items in cell composition(CC),and 74 items in molecular function(MF).KEGG analysis generated 144 signal pathways(P<0.05),involving PI3K-Akt signal pathway,human cytomegalovirus infection,Kaposi's sarcoma-associated herpes virus infection,proteoglycans in cancer,prostate cancer,etc.The results of molecular docking showed that core active compounds such as luteolin andβ-carotene in Sanzi Yangqin Decoction had good affinity with NCOA2,PGR,PTGS2 and other target genes,which were similar to clinically recommended chemical drugs.[Conclusions]The active compounds luteolin and carotene in Sanzi Yangqin Decoction may mainly bind to targets such as NCOA2,PGR,PTGS2,and regulate multiple signaling pathways such as PI3K-Akt to play a role in treating bronchial asthma.It is intended to provide new ideas for the clinical application and research of Sanzi Yangqin Decoction.

Mechanism of Zuojin Pill in the treatment of anxiety disorder and Major depressive disorder based on network pharmacology and molecular docking validation

Background:Zuojin Pill(ZJP)is a classic Chinese herbal prescription with good efficacy in the treatment of Anxiety disorder(AD)and Major depressive disorder(MDD).Nevertheless,the potential mechanisms of ZJP remain unclear.Based on network pharmacology and molecular docking methods,this study aims to elucidate the possible mechanism of ZJP in the treatment of AD and MDD.Methods:The components and targets of Rhizoma Coptidis and Fructus Evodiae were collected from TCMSP,ETCM,HERB,SWISSADME and STITCH databases.The disease targets related to MDD and AD were collected from DISGENET,GENECARDS and OMIM databases.Protein-protein interaction network was constructed by STRING database,GO and KEGG enrichment analysis was performed by METASCAPE database,and“drugs-components-targets network”was constructed by Cytoscape software.Molecular docking verification was performed by Sailvina2.0 software.Results:ZJP may act on AKT1,IL6,TNF and other targets through caffeine,isorhamnetin,berberine and other components,regulating the Inflammatory mediator regulation of TRP channels,Serotonergic synapse,Dopaminergic synapse,PI3K/AKT signaling pathway,and other pathways.The results of molecular docking showed that berberine had the best binding activity with the core target.Conclusion:ZJP can exert anti-anxiety and anti-depression effects through multiple components,multiple targets and multiple pathways.

Molecular mechanisms of Baihedihuang decoction as a treatment for breast cancer related anxiety:A network pharmacology and molecular docking study

BACKGROUND The therapeutic effects of a combination of Chinese medicines called Baihedihuang decoction(BD)have been clinically verified,although its molecular targets in breast cancer related anxiety remain unknown.AIM To explore the molecular mechanisms of BD for breast cancer related anxiety treatment.METHODS We used the Traditional Chinese Medicine Systems Pharmacology database to screen the active ingredients and potential targets of BD,and constructed the"drug-ingredient-target"network map with the help of Cytoscape 3.8 software.Also,we used the Online Mendelian Inheritance in Man,DrugBank,and Gencards databases to collect the disease targets of breast cancer related anxiety,and used the STRING platform to perform protein interaction analysis and construct the protein-protein interaction network.Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key targets.Molecular docking technology was used to verify the drug component/target disease network.RESULTS We screened 16 active ingredients of BD for breast cancer related anxiety,with 113 target proteins.There are 931 disease targets of breast cancer related anxiety,and finally,43 key targets and 305 Kyoto Encyclopedia of Genes and Genomes pathways were generated.The main active ingredients of BD for breast cancer related anxiety are verbascoside,β-sitosterol,stigmasterol,catalpol,etc.CDK2,TP53,HTR2A,ESR1,etc.are its key targets,and the main involved signaling pathways may include neuroactive ligand-receptor interaction pathway,5-hydroxytryptaminergic synapse,P53 signaling pathway,cGMP-PKG signaling pathway,the cAMP signaling pathway,etc.Finally,molecular docking was performed with Vina software to validate the key active ingredients in BD with the selected key action targets.The molecular docking results showed that verbascoside,β-sitosterol,stigmasterol and CDK2 could stably bind and interact through amino acid residues SER249,ARG260,PRO228,ALA282,SER276,LYS273,ASN272,etc.CONCLUSION The therapeutic effect of BD for breast cancer related anxiety is multi-level,multi-target,and multi-pathway.The findings of this study provide ideas and basis for further research.

Exploring the mechanism of action of San Huang lotion for the topical treatment of eczema based on network pharmacology and molecular docking techniques

Objective:To predict the mechanism of action of San Huang lotion for topical treatment of eczema at the level of network pharmacology and molecular docking technology.Methods:The active ingredients and corresponding targets of San Huang lotion were collected using the TCMSP data platform and UniProt;the relevant gene targets of San Huang lotion were collected using the GeneCards database,OMIM database,TTD database,and DrugBank database;the intersection targets of San Huang lotion and eczema were obtained by creating avenn diagram;the key active ingredients and targets were screened by constructing a disease-active ingredient-target map,and the key active ingredients and core targets were screened out by constructing disease-active ingredient-target diagrams and PPInetwork diagrams;GOand KEGGenrichment analyses were conducted using the metascapewebsite and the higher significant entries were selected to produce bar charts and bubble plots.Finally,molecular docking of key active ingredients and core targets was performed.Results:A total of 134 active ingredients and 3,320 eczema-related target genes were screened for San Huang lotion,and 126 intersecting targets were obtained for San Huang lotion and eczema.The five key active ingredients of San Huang lotion for topical treatment of eczema and six core targets ofAKT1,TNF,IL6,IL1B,TP53andVEGFA were obtained by drug-active ingredient-target map and PPInetwork map.The GOand KEGGenrichment analysis showed that the topical treatment of eczema withSanHuanglotion might be mediated throughIL-17signaling pathway,TNFsignaling pathway and Th17cell differentiation pathway.The molecular docking results showed that the docking binding energy of key active ingredients and core targets was mostly less than-5 kcal/mol,and the docking was good.Conclusion:The quercetin,luteolin,wogonin,formononetin,beta-sitosterol and other active ingredients in San Huang lotion may act on eczema through AKT1,TNF,IL6,IL1B,TP53,VEGFA and other targets,and through IL-17signaling pathway,TNFsignaling pathway,Th17cell differentiation and other pathways.

Study on the mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacology and molecular docking

Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresponding target proteins of Shengjiang Xiexin Decoction were screened by TCMSP,and the target of chemotherapy-induced diarrhea were screened by the GeneCards.R software was used to obtain the common targets of drugs and diseases,and the“component-target-disease”network diagram was constructed by Cytoscape3.8.0 software.The string datebase was used to draw the protein interaction(PPI)network,and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets.Result:The result showed that 216 components were screened and 276 effective targets were screened.There were 1764 chemotherapy-induced diarrhea targets.The 173 common targets were obtained through venn diagram.The GO function analysis found 2427 items of biological process,168 items of molecular function and 79 items of cellular component.The KEGG pathway analysis found 169 items.Conclusion:The PPI network found that STAT3、AKT1、MAPK3、JUN、MAPK1、RELA、IL6、etc.may be the key targets for Shengjiang Xiexin Decoction in treatment of chemotherapy-induced diarrhea.GO biological processes include DNA-binding transcription factor activity,cytokine receptor binding,cytokine activity,response to lipopolysaccharide,cellular response to chemical stress and so on.The KEGG pathways involved mainly include Toll-like receptor signaling pathway,TNF signaling pathway,inlfuenza A signaling pathway、hepatitise B signaling pathway and other pathways,that Play the role of anti-inflammatory and repair barrier.

Discussion on the mechanism of Erxian Decoction in the treatment of premature ovarian failure based on network pharmacology and molecular docking

Objective:To explore the mechanism of Erxian Decoction in the treatment of premature ovarian failure.Methods:Based on the method of network pharmacology and molecular docking,the active ingredients of each drug in Erxian Decoction were obtained by searching the TCMSP database;the premature ovarian failure disease targets were collected from the GeneCards,OMIM,PharmGkb and Drugbank databases,and the active ingredients and the disease gene targets were collected Click the intersection to get the predictive target of Erxian Decoction for the treatment of premature ovarian failure.Use Cytoscape 3.8.0 to construct a"drug-component-target-disease"network;construct a protein interaction network(PPI)and streamline the core network through STRING database and Cytoscape;use R Studio software to enrich the Erxiantang treatment POF with GO And KEGG pathway enrichment analysis.Use molecular docking technology to verify the results of the"drug-component-target-disease"network.Results:68 main active ingredients were screened,involving 182 gene targets,among which the main active ingredients include Quercetin,Luteolin,Kaempferol,etc.;The core target genes include RB1,TP53,FOS,CDKN1A,ESR1,AKT1,MAPK1,TNF,etc.;GO enrichment items were obtained,including the 2545 Biological Process(BP),89 Cellular Component(CC),212 Molecular Function(MF);KEGG pathways,including PI3K-Akt signaling pathway,MAPK signaling pathway,and AGE-RAGE signaling pathway in diabetic complications.The verification of the molecular docking results indicated that the main active ingredient has a good binding activity with the core target.Conclusion:This study preliminarily revealed that Erxian Decoction may play a role in the treatment of POF through multi-component,multi-target,and multi-channel synergy,which provides a reference for the next in-depth research.

The Mechanism of Reduning Injection in the Treatment of COVID-19 associated Myocardial Injury Based on Network Pharmacology and Molecular Docking

Objective:To explore the potential active components and mechanism of Reduning injection in the treatment of coronavirus disease 2019(COVID-19)associated myocardial injury by using molecular docking and network pharmacology.Methods:The main chemical constituents and molecular target of Reduning injection were collected from TCMID.Genes related to 2019 ncov were screened by genecards.Cytoscape software was used to construct and analyze the network.The active components of Reduning injection were molecularly docked with a new coronavirus hydrolase and its binding proteins,angiotensin converting enzyme II(ACE2)and transmembrane serine proteases(TMPRSSs).Results:There were 25 active ingredients and 198 drug targets in Reduning injection,43 targets proteins of coronavirus were excavated.Its main components have good binding ability with viral hydrolase and related binding proteins.Conclusion:Reduning injection may intervene the inflammatory response by multi-target and multi-component,inhibit the activity of coronavirus and its binding proteins ACE2 and TMPRSSs,and play a role in the treatment of new coronavirus pneumonia and myocardial injury.

Mechanism of dihydrotanshinone I in the treatment of helicobacter pylori infection based on network pharmacology and molecular docking technology

Objective:Based on the network pharmacology approach and molecular docking technology,the core targets of dihydrotanshinone I(DHT)for the treatment of helicobacter pylori(Hp)infection were searched and the potential mechanisms of drug therapy were explored.Methods:The TCMSPdatabase and Swiss Target Prediction database were employed to identify drug targets.To mine disease targets based on GeneCards,OMIM,DrugBank,DisGeNET,and TTDdatabases.Then the two were intersected to obtain common targets.The proteinproteininteraction(PPI)networkmap of common targets was constructed on the basis of the String network platform and Cytoscape software,and the targets with degree values over 1/2 maximum degree value were selected as core targets.Molecular docking verification of DHTand core targets were performed using AutoDock and PyMOL software.Finally,gene ontology(GO)functional enrichment analysis andKyoto Encyclopediaof Genes and Genomes(KEGG)pathway enrichment analysis of the common targets were carried out using the Metascape database and R-4.0.2-win software.Results:A total of 13 targets of DHTwas extracted for the treatment of Hp,and five core targets,includingSignal transducerand activator of transcription 1(STAT1),Signal transducerand activator of transcription 3(STAT3),Prostaglandin G synthase 2(PTGS2),Signal transducerand activator of transcription 4(STAT4)and Indoleamine 2,3-dioxygenase 1(IDO1),were screened according to their degree values.Molecular docking indicated that DHThad an excellent binding to the core target.29 pathways were yielded by KEGG enrichment analysis,and a total of 48 biological processes,7 cellular components and 13 molecular functions were derived from GO enrichment analysis.Conclusion:DHTmay decrease pro-inflammatory factor expression and immune cell infiltration to treat Hpinfection via the janus kinase(JAK)-signal transducer and activator of transcription(STAT)signaling pathway regulated by STAT1,STAT3,STAT4,etc.

Mechanism of Danggui Sini Decoction(当归四逆汤)for Atherosclerosis Obliterans Based on Network Pharmacology and Molecular Docking

Objective:Based on network pharmacology and molecular docking,we want to explore the pharmacological effects and mechanism of Danggui Sini Decoction in the treatment of lower extremity arteriosclerosis obliterans.Methods:Using TCMSP database to search the main active components of Danggui Sini Decoction(当归四逆汤,DSD)and their related targets,Cytoscape3.8.1 software was used to construct a"component-disease-target"interaction network.Meanwhile,DAVID database was used to enrich the key target genes with GO and KEGG functions.And we used Auto Dock Tools 1.5.6 for molecular docking.Results:A total of 45 candidate active molecules and 250 potential target proteins related to ASO were screened.Key genes such as TNF,IL6,VEGFA,MMP9,IL1B,CCL2,CXCL8,ICAM1,VCAM1,and IL10 are mainly through TNF signaling pathway,HIF-1 signaling pathway,cytokine-cytokine receptor interaction,Toll-like receptor signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway and other biological pathways exert their effects.The results of molecular docking showed that 5UUI-sesamin,5UUI-paeoniflorin,4XCT-sesamin,and 4XCT-sesamin have extremely strong binding ability.Conclusion:Danggui Sini Decoction(当归四逆汤,DSD)can synergistically exert pharmacological effects through multiple components,multiple targets,and multiple pathways.On the basis of regulating immunity and inhibiting smooth muscle proliferation,it can prevent the occurrence and development of ASO.

Analysis of Pharmacodynamic Substance Basis of Fufang Changtai in Treating Colorectal Cancer by UPLC-Q-TOF-MS Combined with Network Pharmacology

[Objectives] To systematically study the main active components of Fufang Changtai(FFCT) in the treatment of colorectal cancer(CRC), and to explore its mechanism of action. [Methods] The main chemical components of FFCT were analyzed by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) combined with automatic analysis platform, and the main pharmacodynamic substances of FFCT were studied by network pharmacology method and its mechanism of action was explored. The binding degree between the active components and the core targets were verified by molecular docking technology. [Results] A total of 86 compounds were identified from FFCT, among which 26 compounds were Ginsenoside Rg3, Ginsenoside Rb1, Astragaloside III, etc. The key target pathway enrichment analysis showed that FFCT played its role in the treatment of CRC mainly through the PI3K-Akt signaling pathway and MAPK signaling pathway. [Conclusions] This study comprehensively identified the FFCT components. Supplemented by network pharmacology and molecular docking technology, it is expected to provide a scientific theoretical basis and an important reference for FFCT therapeutic components identification, key target verification and mechanism of action in the treatment of CRC.

基于网络药理学和生物信息学探讨满药复方木鸡颗粒治疗肝癌的分子机制

利用网络药理学和生物信息学方法揭示复方木鸡颗粒治疗肝癌的作用机制。通过TCMSP、Swiss Target Prediction数据库分别获取复方木鸡颗粒的活性成分以及相关靶点;在GEO数据库筛选肝癌的相关靶点;利用Venny 2.1在线平台获取药物与疾病的共同靶点;由Cytoscape 3.8.2绘制药物–成分–靶点–疾病网络;用STRING数据库构建PPI网络;通过DAVID数据库进行GO功能富集和KEGG通路富集分析;利用Kaplan Meier-Plotter数据库对关键基因的表达量及预后关联性进行分析;运用AutoDock软件对关键成分和靶点进行分子对接验证。复方木鸡颗粒中共获得37个活性成分,筛选出57个共有靶点,涉及生物过程98条、细胞成分17条、分子功能37条,介导15条信号通路。生存期分析结果显示,ESR1、CYP3A4、G6PD基因的表达量与肝癌患者的生存期具有相关性。分子对接表明筛选的6个活性成分与6个关键靶点蛋白之间具有较好的结合能力。复方木鸡颗粒中的大豆皂苷C、柚皮素、β-谷固醇、汉黄芩素等活性成分可以作用于ESR1、CYP3A4、G6PD等靶点,可能通过P53、戊糖磷酸途径、MAPK等信号通路发挥治疗肝癌的作用。

基于网络药理学和分子对接技术探讨沙棘多酚治疗阿尔茨海默病的作用机制

目的基于网络药理学—分子对接技术的方法初步探讨沙棘多酚治疗阿尔兹海默症(Alzheimer’s disease,AD)的作用机制。方法检索中国知网、万方数据库查找目前报道的沙棘多酚化学成分,获得沙棘多酚有效活性成分及预测靶基因。通过Cytoscape 3.8.2软件构建中药—化合物—靶点(基因)网络;采用Gencards、OMIM、DisGeNET等数据库获取AD主要作用靶点,并与化合物基因靶点作韦恩图、明确交集靶点,运用String平台构建蛋白相互作用(PPI)网络模型并挖掘网络中潜在的蛋白质功能模块;通过Metascape平台进行基因本体(GO)功能富集分析及基于京都基因与基因组百科全书(KEGG)通路富集分析,预测其生物过程及作用通路。应用Cytoscape3.8.2软件构建“药物成分-作用靶点-作用通路”网络,运用AutoDock vina软件对核心成分及关键靶点进行分子对接。结果共获得12个沙棘多酚候选化合物、142个成分靶点以及95个沙棘多酚与AD的共同靶点。网络分析结果显示,沙棘多酚调治AD的核心活性成分为阿魏酸、藜芦酸、咖啡酸等,核心靶点包括ALB、EGFR、PTGS2、STAT3、CTNNB1、MMP9、ESR1、TLR4、ICAM1和PPARA。GO和KEGG分析显示,沙棘多酚治疗AD的通路主要富集在化学致癌-受体活化、癌症的通路和糖尿病并发症中的AGE-RAGE信号通路等。其功能主要为氧化还原酶活性、丝氨酸水解酶活性和金属蛋白酶活性等。分子对接研究显示,沙棘多酚的5个关键治疗AD的化合物可与5个核心基因的对接口袋相匹配。结论沙棘多酚可通过多个化合物作用于多个分子靶点和通路发挥对AD的治疗作用。

基于网络药理学和分子对接技术探究脑络欣通治疗缺血性脑卒中的机制

目的采用网络药理学方法探究益气活血方脑络欣通治疗缺血性脑卒中(ischemic stroke,IS)的作用机制,并通过分子对接技术进行初步验证。方法通过TCMSP、ETCM、化学专业数据库及文献筛选脑络欣通活性成分及作用靶点,通过OMIM、DisGeNET、GeneCards以及Drugbank数据库挖掘IS相关靶点;将交集靶点导入STRING平台和Cytoscape 3.8.2软件构建PPI网络并通过拓扑分析获得核心靶点,同时构建“中药—活性成分—核心靶点—疾病”可视化网络图;运用R软件进行GO功能及KEGG通路富集分析。最后借助Auto Dock Tools软件以及PyMOL软件进行分子对接和可视化。结果脑络欣通的潜在活性成分78个,治疗IS的潜在作用靶点200个,核心靶点包括STAT3、JUN、MAPK1、TP53等;作用较突出的活性成分包括槲皮素、β-谷甾醇、山柰酚、木犀草素等。进一步的生物功能分析获得150条信号通路,包括PI3K-AKT信号通路、HIF-1信号通路、FoxO信号通路等关键通路。分子对接结果表明关键活性成分与核心靶点之间存在分子结合位点,并有较强的结合活性。结论益气活血方脑络欣通可能是通过多成分、多靶点协同作用于氧化应激、炎症反应、细胞凋亡、自噬等生理病理环节,从而发挥治疗IS的作用。

网络药理学联合分子对接探究大丁草治疗类风湿关节炎的作用机制

目的:通过网络药理学联合分子对接技术探究大丁草治疗类风湿关节炎的潜在作用机制。方法:选用化学专业数据库、HERB本草组鉴查找大丁草化学成分,经Swiss ADME数据库筛选出有效成分,应用Swiss Target Prediction预测有效成分的潜在靶点,从Gene Cards、OMIM等数据库查筛类风湿关节炎的靶点,应用Venny 2.1.0数据库获得大丁草与类风湿关节炎交集靶点和韦恩图,采用Cytoscape 3.8.2构建大丁草-有效成分-靶点-类风湿关节炎网络并筛选核心成分,利用Cytoscape插件Biso Genet构建交集靶点蛋白质-蛋白质相互作用网络,经2次筛选获得核心靶点,应用Metascape平台对核心靶点进行富集分析,运用Auto Dock vina将5种核心成分与10个核心靶点进行对接。结果:大丁草治疗类风湿关节炎活性成分有大丁草酚、大丁苷等13种,靶点448个,类风湿关节炎靶点618个,交集靶点101个,核心靶点有雌激素受体1(Estrogen Receptor 1,ESR1)、生长因子受体结合蛋白2(Growth Factor Receptor-Bound Protein 2,Grb2)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)等;通过基因本体论(GO)分析获得调节先天免疫反应等条目,通过京都基因与基因组百科全书(KEGG)分析获得磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)、破骨细胞分化、白细胞介素-17(Interleukin 17,IL-17)等92条通路;核心成分与核心靶点有较好的结合活性。结论:大丁草中大丁草酚、大丁苷等核心成分可能通过ESR1、Grb2、EGFR等靶点,调控PI3K-Akt、MAPK等信号通路来治疗类风湿关节炎。