Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by v...Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.展开更多
Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW ...Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW regulates osteogenesis is still unclear.The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis.Methods A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells(BMSCs).Results In total,487 no-repeat targets corresponding to the bioactive components of ZGW were screened,and 175 target genes in the intersection of ZGW and osteogenesis were obtained.And 28 core target genes were then obtained from a PPI network analysis.A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress,metal ions,and lipopolysaccharide.Additionally,KEGG pathway enrichment analysis revealed that multiple signaling pathways,including the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway,were associated with ZGW-promoted osteogensis.Further experimental validation showed that ZGW could increase alkaline phosphatase(ALP)activity as well as the mRNA and protein levels of ALP,osteocalcin(OCN),and runt related transcription factor 2(Runx 2).What’s more,Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT,and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002.Finally,the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002.Conclusion ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.展开更多
Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology me...Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.展开更多
In order to clarify the targets of Xiaoyao Wan in the treatment of depression and anxiety,the pharmacological database of traditional Chinese medicine system and the analysis platform(TCMSP)were used to search the che...In order to clarify the targets of Xiaoyao Wan in the treatment of depression and anxiety,the pharmacological database of traditional Chinese medicine system and the analysis platform(TCMSP)were used to search the chemical components and potential targets of Xiaoyao Wan.The databases of Malacards and Genecards were used to mine the targets related to depression and anxiety.With the help of Cytoscape3.2.1 software,the“Xiaoyao Wan-targets-diseases”network is constructed.The PPI network is constructed through String database.Common targets are enriched by cluster Profiler software package in R language.161 active components of Xiaoyao Wan were screened,and 247 targets related to Xiaoyao Wan were predicted(excluding repetitive targets).The related targets of depression and anxiety were 379,337 respectively.Through the intersection of Venny diagram,24 targets of Xiaoyao Wan,depression and anxiety were obtained.24 key targets were screened out by constructing the interaction network of Xiaoyao Wan,depression and anxiety.Pathway enrichment analysis showed that Xiaoyao Wan mainly acts on key targets involves D(2)dopamine receptor(DRD2),Interleukin-6(IL6),5-hydroxytryptamine receptor 2A(HTR2A),Interleukin-1 beta(IL1B),5-hydroxytryptamine receptor 3A(HTR3A),Sodium-dependent dopamine transporter(SLC6A3),D(1A)dopamine receptor(DRD1),Interleukin-10(IL10),Sodium-dependent noradrenaline transporterin(SLC6A2)and other key targets in the treatment of depression and anxiety,and participates in important pathway processes such as Serotonergic synapse,Dopaminergic synapse,Neuroactive ligand-receptor interaction and regulation of neurotransmitter levels.It is speculated that Xiaoyao Wan plays a role in the treatment of depression and anxiety by affecting neurotransmitters 5-HT and DA,participating in hypothalamic-pituitary-adrenal(HPA)and interfering in the process of inflammation.展开更多
Chronic myeloid leukemia(CML)is a hematopoietic myeloproliferative disorder.The Chinese prescription Danggui Longhui Wan(DGLHW)has been utilized in CML treatment,but its underlying mechanisms remain unclear.In this st...Chronic myeloid leukemia(CML)is a hematopoietic myeloproliferative disorder.The Chinese prescription Danggui Longhui Wan(DGLHW)has been utilized in CML treatment,but its underlying mechanisms remain unclear.In this study,we gathered 794 constituents,1249 drug targets,1654 disease genes and 129 intersection genes.GO and KEGG were used to analyze the function of these genes.Compatibility of prescription study showed that monarch drug,minister drug,assistant and guide drug played a synergistic role in the treatment of CML.In addition,we obtained 20 hub genes and 12 key components.Molecular docking indicated that the main compounds and core proteins had good binding ability.The results of this study also showed that DGLHW might play a role in the treatment of CML by affecting MAPK,PI3K/AKT,FoxO and p53 signaling pathways.展开更多
目的:通过网络药理学的方法探讨桂枝茯苓丸治疗糖尿病肾病(Diabetic Nephropathy,DN)的信号通路及其可能的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analys...目的:通过网络药理学的方法探讨桂枝茯苓丸治疗糖尿病肾病(Diabetic Nephropathy,DN)的信号通路及其可能的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索桂枝茯苓丸中桂枝、茯苓、牡丹、赤芍、桃仁5味中药的有效活性成分,并用Perl软件得出药物作用靶基因,应用Uniprot数据库将药物靶点规范为相应的基因名称;在Genecards数据库、人类孟德尔遗传数据库中输入“diabetic nephropathy”,获取DN的疾病靶点基因。通过R软件获取药物-疾病的交集作用靶点,采用Cytoscape 3.2.1软件绘制成分-靶点-疾病可视化网络图,利用STRING数据库及Cytoscape 3.2.1软件得到靶点蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络图,并进一步对关键靶点进行基因本体论(Gene Ontology,GO)功能富集分析、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果:桂枝茯苓丸药物组成中活性成分有85个,药物靶点有100个,DN疾病靶点有3496个,通过R软件得到交集靶点68个,PPI网络图核心靶点为白细胞介素-6(Interleukin-6,IL-6)、血管内皮生长因子(Vascular Endothelial Growth Factor A,VEGF)A、丝裂原激活蛋白激酶8(Mitogen-Activated Protein Kinase 8,MAPK8)等。GO功能富集分析主要涉及DNA结合转录因子、RNA聚合酶Ⅱ、血红素结合、泛素样蛋白连接酶结合、转录因子结合、核受体活性等。KEGG通路富集分析显示主要涉及流体剪应力与动脉粥样硬化、晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Receptor For Advanced Glycation End Products,RAGE)、细胞凋亡、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1信号通路等。结论:桂枝茯苓丸可能通过多成分、多靶点、多通路实现治疗DN的作用。展开更多
基金supported by Weifang Health Commission Traditional Chinese Medicine Research Project Plan(WFZYY2023-1-004).
文摘Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.
文摘Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW regulates osteogenesis is still unclear.The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis.Methods A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells(BMSCs).Results In total,487 no-repeat targets corresponding to the bioactive components of ZGW were screened,and 175 target genes in the intersection of ZGW and osteogenesis were obtained.And 28 core target genes were then obtained from a PPI network analysis.A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress,metal ions,and lipopolysaccharide.Additionally,KEGG pathway enrichment analysis revealed that multiple signaling pathways,including the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway,were associated with ZGW-promoted osteogensis.Further experimental validation showed that ZGW could increase alkaline phosphatase(ALP)activity as well as the mRNA and protein levels of ALP,osteocalcin(OCN),and runt related transcription factor 2(Runx 2).What’s more,Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT,and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002.Finally,the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002.Conclusion ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.
基金supported by the National Natural Science Foundation of China(81903871)Natural Science Foundation of Jiangsu Province(BK20190565)+1 种基金Fundamental Research Funds for the Central Universities(2632021ZD16)Zhenjiang City 2022 Science and Technology Innovation Fund(SH2022084).
文摘Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.
基金Key discipline project of traditional Chinese medicine pharmaceutical engineering of Shanxi provincial administration of traditional Chinese medicine(2017)Discipline innovation team project of Shanxi university of Chinese medicine(No.2019-YL11)。
文摘In order to clarify the targets of Xiaoyao Wan in the treatment of depression and anxiety,the pharmacological database of traditional Chinese medicine system and the analysis platform(TCMSP)were used to search the chemical components and potential targets of Xiaoyao Wan.The databases of Malacards and Genecards were used to mine the targets related to depression and anxiety.With the help of Cytoscape3.2.1 software,the“Xiaoyao Wan-targets-diseases”network is constructed.The PPI network is constructed through String database.Common targets are enriched by cluster Profiler software package in R language.161 active components of Xiaoyao Wan were screened,and 247 targets related to Xiaoyao Wan were predicted(excluding repetitive targets).The related targets of depression and anxiety were 379,337 respectively.Through the intersection of Venny diagram,24 targets of Xiaoyao Wan,depression and anxiety were obtained.24 key targets were screened out by constructing the interaction network of Xiaoyao Wan,depression and anxiety.Pathway enrichment analysis showed that Xiaoyao Wan mainly acts on key targets involves D(2)dopamine receptor(DRD2),Interleukin-6(IL6),5-hydroxytryptamine receptor 2A(HTR2A),Interleukin-1 beta(IL1B),5-hydroxytryptamine receptor 3A(HTR3A),Sodium-dependent dopamine transporter(SLC6A3),D(1A)dopamine receptor(DRD1),Interleukin-10(IL10),Sodium-dependent noradrenaline transporterin(SLC6A2)and other key targets in the treatment of depression and anxiety,and participates in important pathway processes such as Serotonergic synapse,Dopaminergic synapse,Neuroactive ligand-receptor interaction and regulation of neurotransmitter levels.It is speculated that Xiaoyao Wan plays a role in the treatment of depression and anxiety by affecting neurotransmitters 5-HT and DA,participating in hypothalamic-pituitary-adrenal(HPA)and interfering in the process of inflammation.
文摘Chronic myeloid leukemia(CML)is a hematopoietic myeloproliferative disorder.The Chinese prescription Danggui Longhui Wan(DGLHW)has been utilized in CML treatment,but its underlying mechanisms remain unclear.In this study,we gathered 794 constituents,1249 drug targets,1654 disease genes and 129 intersection genes.GO and KEGG were used to analyze the function of these genes.Compatibility of prescription study showed that monarch drug,minister drug,assistant and guide drug played a synergistic role in the treatment of CML.In addition,we obtained 20 hub genes and 12 key components.Molecular docking indicated that the main compounds and core proteins had good binding ability.The results of this study also showed that DGLHW might play a role in the treatment of CML by affecting MAPK,PI3K/AKT,FoxO and p53 signaling pathways.
文摘目的:通过网络药理学的方法探讨桂枝茯苓丸治疗糖尿病肾病(Diabetic Nephropathy,DN)的信号通路及其可能的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索桂枝茯苓丸中桂枝、茯苓、牡丹、赤芍、桃仁5味中药的有效活性成分,并用Perl软件得出药物作用靶基因,应用Uniprot数据库将药物靶点规范为相应的基因名称;在Genecards数据库、人类孟德尔遗传数据库中输入“diabetic nephropathy”,获取DN的疾病靶点基因。通过R软件获取药物-疾病的交集作用靶点,采用Cytoscape 3.2.1软件绘制成分-靶点-疾病可视化网络图,利用STRING数据库及Cytoscape 3.2.1软件得到靶点蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络图,并进一步对关键靶点进行基因本体论(Gene Ontology,GO)功能富集分析、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果:桂枝茯苓丸药物组成中活性成分有85个,药物靶点有100个,DN疾病靶点有3496个,通过R软件得到交集靶点68个,PPI网络图核心靶点为白细胞介素-6(Interleukin-6,IL-6)、血管内皮生长因子(Vascular Endothelial Growth Factor A,VEGF)A、丝裂原激活蛋白激酶8(Mitogen-Activated Protein Kinase 8,MAPK8)等。GO功能富集分析主要涉及DNA结合转录因子、RNA聚合酶Ⅱ、血红素结合、泛素样蛋白连接酶结合、转录因子结合、核受体活性等。KEGG通路富集分析显示主要涉及流体剪应力与动脉粥样硬化、晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Receptor For Advanced Glycation End Products,RAGE)、细胞凋亡、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1信号通路等。结论:桂枝茯苓丸可能通过多成分、多靶点、多通路实现治疗DN的作用。