Objective Pharmacological methods were used to screen targets and signaling pathways of Ma Xing Shi Gan Decoction(MXSGD)during influenza treatments,and mechanisms underlying antiinfluenza effects were elucidated.Metho...Objective Pharmacological methods were used to screen targets and signaling pathways of Ma Xing Shi Gan Decoction(MXSGD)during influenza treatments,and mechanisms underlying antiinfluenza effects were elucidated.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and relevant literature were searched under predefined conditions to identify the main compounds and their targets.Interactions between the target proteins were predicted using the STRING database.Gene Ontology(GO)functional enrichment analyses and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed on the core targets involved in the influenza protein-protein interaction(PPI)network,using WebGestalt and the reactome database.iGEMDOCK was used for molecular docking of receptors and ligands to produce docking scores,and the results were visualized using Autodock and PyMOL.Results In total,126 major compounds and their respective targets were screened.355 influenza target proteins and 1221 influenza protein interactions were predicted using the STRING database.Influenza-related signaling pathways were strongly enriched in pharmacodynamic targets of MXSGD such as cytokine signaling in immune system and signaling by interleukin.The main biological process was response to the stimulates.Molecular docking results showed that RELALicochalcone A docking elicited by MXSGD,was superior to that of other target proteins and active compounds,suggesting that the docking site is also the main effector site of MXSGD during influenza treatments.Conclusions The results showed that MXSGD exerts antiinfluenza effects by interfering with virus adsorption,inhibiting virus proliferation,influencing immune functions and protecting host cells,which may prevent inflammation-induced tissue damage.展开更多
Objective:To explore and verify the mechanism of Gan Dou Ling in improving liver fibrosis in Wilson disease(WD)by network pharmacology and copper loaded mice experiments.Methods:The main chemical components and corres...Objective:To explore and verify the mechanism of Gan Dou Ling in improving liver fibrosis in Wilson disease(WD)by network pharmacology and copper loaded mice experiments.Methods:The main chemical components and corresponding gene targets of each drug in Gan Dou Ling were obtained by using TCMSP database.The database of gene mutation and disease related gene was searched through the GeneCards database,DrugBank database,PharmGKB database and the DisGeNET database.After the intersection of drug and disease target genes.The STRING website was used to analyze the protein-protein interaction degree of target genes,and import the data to Cytoscape software 38.2 to analyze protein interaction network.The GO databases and KEGG databases were obtained in R language for enrichment analysis.On this basis,Masson staining were used to observe the degree of liver fibrosis in copper loaded mouse model,and the results of network pharmacological analysis were verified by Western Blot(WB).Results:A total of 108 drug disease intersection genes were analyzed by network pharmacology.Through PPI network analysis,JUN was found to be the key genes.The enrichment analysis of KEGG pathway showed that MAPK signal pathway was the important potential target pathways.Animal experiments showed that Gan Dou Ling could reduce liver fibrosis and inhibit the phosphorylation of P38,JNK and C-JUN in copper loaded mice.Conclusion:Gan Dou Ling may achieve the effect of treating WD liver fibrosis by inhibiting P38/JNK signaling pathway.展开更多
Objective To use systematic pharmacological strategies to explore the regulatory mechanisms of Ma Xing Shi Gan Decoction(MXSGD)against the coronavirus disease 2019(COVID-19).Methods Data on the compounds and targets o...Objective To use systematic pharmacological strategies to explore the regulatory mechanisms of Ma Xing Shi Gan Decoction(MXSGD)against the coronavirus disease 2019(COVID-19).Methods Data on the compounds and targets of MXSGD were collected from the Traditional Chinese Medicene Systems Parmacology Database and Analysis Platform(TCMSP)and TCM Databases@Taiwan.Data on ACE2-related targets and the protein-protein interaction(PPI)were collected from the String database.The Cytoscape 3.7.2 was used to construct and analyze the networks.The DAVID platform was used for Gene Ontology(GO)and pathway enrichment analyses.Results Data on 272 MXSGD targets and 21 SARS-CoV-2 potential targets were collected.Four networks were constructed and analyzed based on the data:(1)compound-target network of MXSGD;(2)MXSGD-SARS-CoV-2-PPI network;(3)cluster of MXSGD-SARS-CoV-2-PPI network;(4)Herb-Pathway-Target network.The core targets included AKT1,MAPK3,IL-6,TP53,VEGFA,TNF,CASP3,EGFR,EGF and MAPK1.The antiviral biological processes were inflammatory responses(inflammatory cells,inflammatory cytokines and their signaling pathways),immune responses(T cells,monocytes,B cells and other immune cells),immune factors(IFN-γ,TNF-αand so on),virus defense,humoral immunity and mucosal innate immune response.The antivirus-related signaling pathways included TNF,NOD-like receptor,FoxO,PI3K-AKT and Toll-like receptor signaling pathways.Conclusions MXSGD can control disease progression by regulating multiple compounds and targets;it can reduce inflammation and balance immunity by regulating several proteins that interact with ACE2 and signaling pathways closely related to disease development.展开更多
目的通过网络药理学和分子对接,预测柴胡疏肝散(Chai Hu Shu Gan San,CHSGS)治疗肝细胞癌(Hepatocellular carcinoma,HCC)的分子靶点,构建预后模型和列线图。方法从TCGA和GEO数据库筛选出差异表达基因、加权共表达基因和聚类模块与正常...目的通过网络药理学和分子对接,预测柴胡疏肝散(Chai Hu Shu Gan San,CHSGS)治疗肝细胞癌(Hepatocellular carcinoma,HCC)的分子靶点,构建预后模型和列线图。方法从TCGA和GEO数据库筛选出差异表达基因、加权共表达基因和聚类模块与正常组的差异基因;将四者取交集,得到HCC发生发展密切相关的基因;从TCMSP和SymMap数据库下载CHSGS的化合物和靶点,进一步将CHSGS的靶点与HCC相关基因进行取交集得到治疗HCC相关靶点,将其治疗HCC相关靶点进行GO和KEGG功能富集分析;使用SymMap数据库,构建CHSGS治疗HCC“病-证-方/药”网络。将PPI和构建的药物靶点网络取交集,得到核心的靶点,进一步使用cox LASSO回归分析构建相关的预后模型;结合临床性状使用单因素和多因素cox分析构建列线图;使用分子对接评估分子靶点的结合情况。使用人类蛋白质图谱(HPA)数据库进行核心靶点的免疫组织化学染色验证。结果得到了HCC发生发展密切相关基因890个。CHSGS治疗HCC靶点38个。GO和KEGG分析显示,CHSGS治疗HCC可能与对无机物的反应、类固醇代谢过程和对细胞外刺激的反应有关;CHSGS治疗HCC可能与FOXM1信号通路有关。cox LASSO回归构建了预后模型,其模型公式为:(0.1165)*CCNB1+(-0.0396)*PON1+(0.0888)*CHEK1+(0.0521)*SPP1+(0.0093)*NQO1+(0.0102)*SERPINE1+(0.0012)*IGFBP3。单因素cox联合多因素cox分析显示,ESR1、T分期是独立的预后危险因素。列线图结果显示,其c-index为0.622,P<0.001。分子对接结果显示,异鼠李素与ESR1的结合良好。免疫组织化学染色结果在蛋白质水平验证了结果的准确性。结论异鼠李素可能是CHSGS治疗HCC的主要成分之一,CHSGS治疗HCC的靶点用以构建的预后模型可以用于患者预后的评估,根据ESR1的表达水平、T分期构建的列线图可用于患者总体生存率的估算。展开更多
利用网络药理学方法预测加味甘草附子汤(modified Gan Cao Fu Zi Decoction, GCFZ)治疗类风湿关节炎(rheumatoid arthritis, RA)的作用机制,通过动物实验验证分析结果并探讨GCFZ的药效学效果。首先利用TCMID、SymMap、HERB、STITCH和GE...利用网络药理学方法预测加味甘草附子汤(modified Gan Cao Fu Zi Decoction, GCFZ)治疗类风湿关节炎(rheumatoid arthritis, RA)的作用机制,通过动物实验验证分析结果并探讨GCFZ的药效学效果。首先利用TCMID、SymMap、HERB、STITCH和GEO数据库获取GCFZ治疗RA的靶基因,共筛选得到RA差异表达基因1 250个, GCFZ靶点基因534个,交集基因83个。随后通过GO和KEGG数据库对交集基因进行功能富集分析,发现GCFZ及其活性成分主要通过细胞因子通路发挥作用,其中趋化因子信号通路、肿瘤坏死因子(tumor necrosis factor, TNF)信号通路富集基因数较多。接着使用Cytoscape3.8.0软件构建药物-靶点-疾病网络并筛选到TNF、趋化因子8 (C-X-C chemokine ligand 8, CXCL8)、趋化因子10 (C-X-C chemokine ligand 10, CXCL10)、趋化因子配体5(C-Cchemokineligand5,CCL5)、趋化因子2(C-X-Cchemokineligand2,CXCL2)、趋化因子受体4(C-X-C chemokine receptor type 4, CXCR4)等6个核心蛋白,并通过分子对接技术验证GCFZ主要活性成分与核心蛋白结合能力。通过构建胶原诱导性关节炎(collagen-induced arthritis, CIA)大鼠模型探讨GCFZ低、中、高(4、8、16 g·kg^(-1))剂量组的治疗效果, X射线影像学方法、HE染色、番红O-固绿染色结果显示, GCFZ干预能显著改善CIA大鼠骨质破坏、滑膜增生和软骨损伤,免疫荧光结果显示GCFZ治疗能够调节TNF、CXCL8、CCL5的表达。综上,本研究结果表明GCFZ含有多种小分子药效物质,能够通过多靶点、多通路发挥治疗作用,明显减轻CIA大鼠的关节炎症状。本研究动物实验获得蚌埠医学院实验动物管理和伦理委员会批准。展开更多
基金We thank for the funding support from the National Natural Science Foundation of China(No.81973670)the Natural Science Foundation of Hunan Province(No.2018JJ2297)+1 种基金the Key Program of Scientific Research Fund of Hunan Provincial Education Department(No.19A370)the Project of Research Learning and Innovative Experiment for College Students in Hunan(No.2016284,No.2016281,No.2017281and No.2018420).
文摘Objective Pharmacological methods were used to screen targets and signaling pathways of Ma Xing Shi Gan Decoction(MXSGD)during influenza treatments,and mechanisms underlying antiinfluenza effects were elucidated.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and relevant literature were searched under predefined conditions to identify the main compounds and their targets.Interactions between the target proteins were predicted using the STRING database.Gene Ontology(GO)functional enrichment analyses and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed on the core targets involved in the influenza protein-protein interaction(PPI)network,using WebGestalt and the reactome database.iGEMDOCK was used for molecular docking of receptors and ligands to produce docking scores,and the results were visualized using Autodock and PyMOL.Results In total,126 major compounds and their respective targets were screened.355 influenza target proteins and 1221 influenza protein interactions were predicted using the STRING database.Influenza-related signaling pathways were strongly enriched in pharmacodynamic targets of MXSGD such as cytokine signaling in immune system and signaling by interleukin.The main biological process was response to the stimulates.Molecular docking results showed that RELALicochalcone A docking elicited by MXSGD,was superior to that of other target proteins and active compounds,suggesting that the docking site is also the main effector site of MXSGD during influenza treatments.Conclusions The results showed that MXSGD exerts antiinfluenza effects by interfering with virus adsorption,inhibiting virus proliferation,influencing immune functions and protecting host cells,which may prevent inflammation-induced tissue damage.
基金supported by the National Natural Science Foundation of China(No.81973825)the Natural Science Research Foundation of Anhui Province Universities(No.KJ2020A0436)。
文摘Objective:To explore and verify the mechanism of Gan Dou Ling in improving liver fibrosis in Wilson disease(WD)by network pharmacology and copper loaded mice experiments.Methods:The main chemical components and corresponding gene targets of each drug in Gan Dou Ling were obtained by using TCMSP database.The database of gene mutation and disease related gene was searched through the GeneCards database,DrugBank database,PharmGKB database and the DisGeNET database.After the intersection of drug and disease target genes.The STRING website was used to analyze the protein-protein interaction degree of target genes,and import the data to Cytoscape software 38.2 to analyze protein interaction network.The GO databases and KEGG databases were obtained in R language for enrichment analysis.On this basis,Masson staining were used to observe the degree of liver fibrosis in copper loaded mouse model,and the results of network pharmacological analysis were verified by Western Blot(WB).Results:A total of 108 drug disease intersection genes were analyzed by network pharmacology.Through PPI network analysis,JUN was found to be the key genes.The enrichment analysis of KEGG pathway showed that MAPK signal pathway was the important potential target pathways.Animal experiments showed that Gan Dou Ling could reduce liver fibrosis and inhibit the phosphorylation of P38,JNK and C-JUN in copper loaded mice.Conclusion:Gan Dou Ling may achieve the effect of treating WD liver fibrosis by inhibiting P38/JNK signaling pathway.
基金the funding support from the National Natural Science Foundation of China(No.81774126,No.81973670)the Natural Science Foundation of Hunan Province(No.2016JJ2095,No.2017JJ3232)+2 种基金Scientific Research Project of Traditional Chinese Medicine for the Prevention and Treatment of New Pneumonia in Hunan Province(No.GYGG007)the Construction Project of Specialty of Traditional Chinese Medicine in Guangdong Provincethe Construction Project of Specialty of Traditional Chinese Medicine in Shenzhen。
文摘Objective To use systematic pharmacological strategies to explore the regulatory mechanisms of Ma Xing Shi Gan Decoction(MXSGD)against the coronavirus disease 2019(COVID-19).Methods Data on the compounds and targets of MXSGD were collected from the Traditional Chinese Medicene Systems Parmacology Database and Analysis Platform(TCMSP)and TCM Databases@Taiwan.Data on ACE2-related targets and the protein-protein interaction(PPI)were collected from the String database.The Cytoscape 3.7.2 was used to construct and analyze the networks.The DAVID platform was used for Gene Ontology(GO)and pathway enrichment analyses.Results Data on 272 MXSGD targets and 21 SARS-CoV-2 potential targets were collected.Four networks were constructed and analyzed based on the data:(1)compound-target network of MXSGD;(2)MXSGD-SARS-CoV-2-PPI network;(3)cluster of MXSGD-SARS-CoV-2-PPI network;(4)Herb-Pathway-Target network.The core targets included AKT1,MAPK3,IL-6,TP53,VEGFA,TNF,CASP3,EGFR,EGF and MAPK1.The antiviral biological processes were inflammatory responses(inflammatory cells,inflammatory cytokines and their signaling pathways),immune responses(T cells,monocytes,B cells and other immune cells),immune factors(IFN-γ,TNF-αand so on),virus defense,humoral immunity and mucosal innate immune response.The antivirus-related signaling pathways included TNF,NOD-like receptor,FoxO,PI3K-AKT and Toll-like receptor signaling pathways.Conclusions MXSGD can control disease progression by regulating multiple compounds and targets;it can reduce inflammation and balance immunity by regulating several proteins that interact with ACE2 and signaling pathways closely related to disease development.
文摘目的通过网络药理学和分子对接,预测柴胡疏肝散(Chai Hu Shu Gan San,CHSGS)治疗肝细胞癌(Hepatocellular carcinoma,HCC)的分子靶点,构建预后模型和列线图。方法从TCGA和GEO数据库筛选出差异表达基因、加权共表达基因和聚类模块与正常组的差异基因;将四者取交集,得到HCC发生发展密切相关的基因;从TCMSP和SymMap数据库下载CHSGS的化合物和靶点,进一步将CHSGS的靶点与HCC相关基因进行取交集得到治疗HCC相关靶点,将其治疗HCC相关靶点进行GO和KEGG功能富集分析;使用SymMap数据库,构建CHSGS治疗HCC“病-证-方/药”网络。将PPI和构建的药物靶点网络取交集,得到核心的靶点,进一步使用cox LASSO回归分析构建相关的预后模型;结合临床性状使用单因素和多因素cox分析构建列线图;使用分子对接评估分子靶点的结合情况。使用人类蛋白质图谱(HPA)数据库进行核心靶点的免疫组织化学染色验证。结果得到了HCC发生发展密切相关基因890个。CHSGS治疗HCC靶点38个。GO和KEGG分析显示,CHSGS治疗HCC可能与对无机物的反应、类固醇代谢过程和对细胞外刺激的反应有关;CHSGS治疗HCC可能与FOXM1信号通路有关。cox LASSO回归构建了预后模型,其模型公式为:(0.1165)*CCNB1+(-0.0396)*PON1+(0.0888)*CHEK1+(0.0521)*SPP1+(0.0093)*NQO1+(0.0102)*SERPINE1+(0.0012)*IGFBP3。单因素cox联合多因素cox分析显示,ESR1、T分期是独立的预后危险因素。列线图结果显示,其c-index为0.622,P<0.001。分子对接结果显示,异鼠李素与ESR1的结合良好。免疫组织化学染色结果在蛋白质水平验证了结果的准确性。结论异鼠李素可能是CHSGS治疗HCC的主要成分之一,CHSGS治疗HCC的靶点用以构建的预后模型可以用于患者预后的评估,根据ESR1的表达水平、T分期构建的列线图可用于患者总体生存率的估算。
