基于网络药理学和分子对接探索桑白皮治疗糖尿病周围神经病变的潜在机制

本研究运用网络药理学和分子对接方法对中药桑白皮治疗糖尿病周围神经病变(DPN)的活性成分、潜在作用靶点和信号通路进行研究,探索桑白皮治疗DPN的可能作用机制。首先从中药系统药理学数据库(TCMSP)筛选出桑白皮的活性成分及靶点基因。通过GeneCards数据库及OMIM数据库筛选出DPN的疾病靶点基因,并用Cytoscape软件构建"药物-有效成分-靶基因-疾病"中药调控网络图。将有效成分靶标与疾病靶标上传到STRING数据库,构建蛋白互作网络图(PPI),并使用R语言对得到的PPI进行核心基因的筛选。运用R语言对关键靶点进行GO富集分析和KEGG通路富集分析。其次从活性成分及靶点基因中根据degree值筛选出前3个关键成分,并将该网络中的基因靶点以degree值高低进行排序,选择前3个核心靶点,然后从RCSB数据库下载相关蛋白的结构,使用Pymol软件去除溶剂分子与配体,使用AutoDock软件进行分子对接。最后通过酶联免疫吸附实验和荧光光谱实验验证网络药理学富集分析的结果。最终预测到31个桑白皮活性成分,312个活性成分相关靶点,120个桑白皮-糖尿病周围神经病变共同有效靶点。活性...     

基于网络药理学和分子对接探讨银杏叶治疗高血压病潜在作用机制

通过网络药理学和分子对接技术探讨银杏叶治疗高血压的潜在作用机制.首先,通过TCMSP、Swiss Target Prediction、Uniprot等数据库获取银杏叶的化学成分与对应靶点;运用OMIM、DrugBank及Gencards疾病数据库搜索高血压相关靶点.然后,取银杏叶对应靶点与高血压相关靶点的交集即可得到银...     

基于网络药理学和分子对接技术探讨冬虫夏草治疗肾纤维化的潜在作用机制

为了探究冬虫夏草治疗肾纤维化的分子机制,本研究运用网络药理学方法筛选出冬虫夏草抗肾纤维化的活性成分、潜在作用靶点及相关信号通路,并对关键的化合物和靶点进行分子对接。结果表明,冬虫夏草共有22个化合物和364个潜在靶点参与治疗肾纤维化,蛋白互作（PPI）分析出IL-6、TNF-α、MAPK3、EGFR、SRC、CASP3和MAPK1等关键潜在靶点,KEGG通路富集筛选得到163条信号通路。分子对接结果显示,冬虫夏草治疗肾纤维化过程中,其核心化合物金色酰胺醇酯、啤酒甾醇、酒渣碱、花生四烯酸、11,14-二十碳二烯酸分别与PIK3CA、PIK3CB、PIK3CD、MAPK1、MAPK3、RELA等具有良好的结合性能。分析结果显示,冬虫夏草具有通过多成分、多靶点、多通路减缓肾纤维化的潜力,为其抗肾纤维化临床使用提供了一定的依据。     

基于网络药理学的谷糠结合态多酚抗乳腺癌机制研究

本研究旨在探讨谷糠结合态多酚(bound phenol of inner shell,BPIS)发挥抗乳腺癌细胞活性的作用机制。首先采用细胞计数法检测BPIS对乳腺癌细胞以及正常乳腺细胞活性的影响;然后综合运用SEA、SIB以及GeneCards等数据库获得BPIS和乳腺癌的相关靶点,并分析活性成分与作用靶点的互作网络以及通路。本研究筛选得到BPIS抗乳腺癌相关靶点39个,主要涉及糖脂代谢和细胞自噬等生物过程以及MAPK、PI3K/AKT、FoxO等多条信号通,表明BPIS抗乳腺癌是多成分、多靶点、多通路协同作用的过程,而与细胞死亡相关的细胞自噬很可能在BPIS抑制乳腺癌过程中发挥主要作用。     

基于网络药理学、分子对接和实验验证探讨朱茯苓用于失眠的作用机制

为探讨朱茯苓治疗失眠的可能作用机制,通过TCMSP、BAT-MAN、TCMID和STITCH数据库以及文献挖掘筛选朱茯苓的活性成分及潜在靶点,利用TTD、OMIM、GeneCards和CTD数据库获取失眠类疾病的相关靶点,采用Cyto-scape软件和String数据库构建活性成分-靶点网络和靶点蛋白相互作用网络,通过...     

基于网络药理学的柿果药理功能定位及作用机制

基于网络药理学,通过国内外文献检索获取柿果中的化合物,采用Swiss target prediction数据库对化合物进行潜在靶点垂钓以探讨柿果的药理功能定位及作用机制。以Cytoscape软件构建化合物-靶点网络,靶点-疾病名称-疾病分类网络,同时对靶点进行蛋白相互作用(PPI)网络构建,采用DAVID数据库对靶点进行通路富集分析。本研究共收集到柿果中16个化合物,可作用于68个靶点,这些靶点主要作用于心血管疾病、神经精神性疾病等。PPI网络图包含84个节点,226条边,其中degree值排前10的关键蛋白分别为ERS1、PGS2、MMP2、TIMP1、MMP9、MMP1、AR、SLC6A3、PRKCB、CYP19A1。上述靶点可调节氮素代谢、血清素能突触以及TRP通道炎症介质的调节等信号通路。本研究为阐明柿果的药理功能定位及其作用机制研究提供了可靠的依据。     

基于网络药理学和分子对接技术探究清震汤治疗偏头痛的作用机制

基于网络药理学及分子对接技术探究清震汤治疗偏头痛的作用机制。利用中药系统药理学平台,结合文献报道,获取清震汤中3味中药的活性成分和作用靶点,借助UniProt数据库对靶点蛋白名称进行规范。通过DrugBank、GeneCards等数据库获取偏头痛相关靶点。运用在线Venny作图平台,得到清震汤治疗偏头痛的潜在作用靶点。通过STRING平台构建潜在靶点PPI网络,将所得蛋白互作信息导入Cytoscape 3.7.1进行图像优化及提取核心基因,运用DAVID数据库对潜在作用靶点进行富集分析,采用Cytoscape 3.7.1构建“中药-化合物-靶点-通路”调控网络并进行拓扑分析,使用Autodock软件进行分子对接验证。网络药理学分析结果显示,清震汤中治疗偏头痛可能与槲皮素、山奈酚、豆甾醇等40个化学成分有关,IL6、CXCL8、TNF、PTGS2等为关键靶点。富集分析得到GO条目436条,KEGG通路92条,主要涉及TNF信号通路,神经信号传递通路等。分子对接结果显示,上述活性成分与相关靶点具有较好的结合活性。该研究初步表明,清震汤中多种活性成分通过作用于IL6、CXCL8、TNF、PT...     

Exploring the mechanism of ellagic acid against gastric cancer based on bioinformatics analysis and network pharmacology

Ellagic acid (EA) is a natural polyphenolic compound. Recent studies have shown that EA has potential anticancer properties against gastric cancer (GC). This study aims to reveal the potential targets and mechanisms of EA against GC. This study adopted methods of bioinformatics analysis and network pharmacology, including the weighted gene co-expression network analysis (WGCNA), construction of protein–protein interaction (PPI) network, receiver operating characteristic (ROC) and Kaplan–Meier (KM) survival curve analysis, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics simulations (MDS). A total of 540 EA targets were obtained. Through WGCNA, we obtained a total of 2914 GC clinical module genes, combined with the disease database for screening, a total of 606 GC-related targets and 79 intersection targets of EA and GC were obtained by constructing Venn diagram. PPI network was constructed to identify 14 core candidate targets; TP53, JUN, CASP3, HSP90AA1, VEGFA, HRAS, CDH1, MAPK3, CDKN1A, SRC, CYCS, BCL2L1 and CDK4 were identified as the key targets of EA regulation of GC by ROC and KM curve analysis. The enrichment analysis of GO and KEGG pathways of key targets was performed, and they were mainly enriched in p53 signalling pathway, PI3K-Akt signalling pathway. The results of molecular docking and MDS showed that EA could effectively bind to 13 key targets to form stable protein–ligand complexes. This study revealed the key targets and molecular mechanisms of EA against GC and provided a theoretical basis for further study of the pharmacological mechanism of EA against GC.     

基于网络药理学的四君子汤治疗阿尔茨海默病作用机制研究

基于网络药理学探讨四君子汤治疗阿尔茨海默病(AD)的作用机制.借助TCMSP数据库及Uniprot数据库筛选出四君子汤有效成分及靶点基因.通过Drugbank、Dis Ge NET和TTD数据库筛选出阿尔茨海默病的靶点基因;成分靶点与疾病靶点映射后使用Cytoscape 3.7.1软件构建药物有效成分-靶点蛋白相互作用...     

基于网络药理学分析瑞香素抗多种肿瘤的作用机制及体外实验验证

基于网络药理学预测瑞香素抗恶性胶质瘤、肝癌和三阴性乳腺癌的共同靶点及可能机制,并对其进行体外实验验证。利用Swiss Target Prediction和GeneCards等数据库检索瑞香素与恶性胶质瘤、肝癌和三阴性乳腺癌的共同靶点。使用Cytoscape构建瑞香素-三种肿瘤蛋白质相互作用网络图(PPI)并筛选出核心靶点,并对核心靶点进行GO及KEGG富集分析;通过AutoDock Tools对瑞香素与核心靶点进行分子对接。体外实验验证:采用CCK-8和Western blot法行体外实验验证不同浓度瑞香素对U-251 MG、HepG-2和MDA-MB231细胞系细胞抑制率和P53、RRM2蛋白的表达水平的影响。共筛选出瑞香素抗三种肿瘤核心靶点56个,富集分析显示靶点富集在P53通路和癌症通路,参与细胞周期调节、细胞凋亡、DNA生物合成和修复等生物过程;分子对接结果显示瑞香素与P53、RRM2有较好的结合作用。体外验证实验显示,与对照组比较,瑞香素能显著抑制U-251 MG、HepG-2、MDA-MB231的增殖(P<0.01),并显著上调其P53蛋白及下调RRM2蛋白的表达,且...     

基于网络药理学探讨“黄芪-白术-熟地黄”组方防治肾病综合征的作用机制

本研究旨在通过网络药理学方法和分子对接技术探讨黄芪-白术-熟地黄组方(HBS)治疗肾病综合征的作用机制.通过多个数据库获取肾病综合征基因并进行功能模块分解,找出肾病综合征基因参与的主要生物学过程.通过文献以及数据库查找HBS活性成分和基因靶点,筛选出HBS治疗肾病综合征的有效靶点.通过有效靶点的KEGG和GO富集分析,...     

基于网络药理学探讨丹参-丹皮配伍抗脑缺血损伤的作用机制

本文旨在通过网络药理学和分子对接方法探讨丹参-丹皮活性成分治疗脑卒中的潜在分子机制.首先基于中药系统药理学分析平台筛选丹参、丹皮的活性成分及其作用靶点,利用CTD、TTD和GeneCards数据库收集脑卒中相关靶点.然后将药物和疾病靶点取交集,借助STRING数据库获取靶点间相互作用关系,利用R语言的Cluster-P...     

Revealing mechanism of Caulis Sargentodoxae for the treatment of ulcerative colitis based on network pharmacology approach

Objective: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches.Materials and methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets.Results: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways.Conclusion: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway.     

基于网络药理学的大黄治疗阿尔茨海默病作用机制研究

基于网络药理学探讨大黄治疗阿尔茨海默病(AD)的作用机制.借助TCMSP数据库及Uniprot数据库筛选出大黄有效成分及靶点基因.通过Drugbank、Dis Ge NET和TTD数据库筛选出阿尔茨海默病的靶点基因;成分靶点与疾病靶点映射后使用Cytoscape 3.7.1软件构建药物有效成分-靶点蛋白相互作用网络,使...     

基于网络药理学及分子对接的浙贝母花-枇杷花药对止咳化痰作用机制研究

采用网络药理学及分子对接阐明浙贝母花—枇杷花药对的止咳化痰作用机制.以口服生物利用度≥30％和类药性≥0.18筛选成分,Swiss Target Prediction数据库进行靶点预测,GenCLiP 3和Drugbank数据库进行疾病靶点分析.以STRING和Cytoscape软件构建成分—靶点互作图,并进行GO、K...     

基于网络药理学的杜仲-山茱萸配伍治疗糖尿病的作用机制

为探讨杜仲-山茱萸治疗糖尿病的作用机制。研究利用网络药理学的方法,首先通过中药系统药理学数据库筛选出杜仲和山茱萸的活性成分和相关靶点,再利用DisGeNET、DrugBank等数据库筛选出糖尿病的潜在靶点。以STRING数据库对活性靶点构建蛋白互作网络(PPI)分析,采用Cytoscape3.7.0软件绘制其“成分-靶点-通路”的相互作用网络,通过CludterProfiler对靶蛋白进行生物过程、细胞组分及分子功能分析;京都基因与基因组(KEGG)的代谢通路分析。实验结果筛选得到杜仲-山茱萸有效成分30个,其中槲皮素、山奈酚、β-谷甾醇等成分对PTGS2、DPP4、ADRB2、PPARG等相关靶点通过IL-17信号通路、钙信号通路、脂肪细胞脂解的调控等参与氮化合物代谢过程、血液循环、脂肪细胞分化和血压调节等过程。综上,杜仲-山茱萸配伍治疗糖尿病存在多成分和多重药理作用机制,为进一步研究其治疗糖尿病药理实验提供了参考,也为其他中药的相关研究提供借鉴和参考。     

基于HPLC-Q-TOF-MS/MS技术的蒲公英化学成分分析及其抗癌机制的网络药理学研究

为了探究蒲公英主要成分,分析其抗癌的可能机制及作用靶点,借助HPLC-Q-TOF-MS/MS技术对蒲公英提取物进行分析,利用SwissADME、Swiss Target Prediction和GeneCards数据库获取蒲公英主要活性成分和抗癌的作用靶点,通过String在线数据库构建靶蛋白相互作用网络,并利用DVIAD在线数据库对关键靶点进行GO和KEGG富集分析。最终从蒲公英提取物中共鉴定出29个化合物,主要包括有机酸类、黄酮类等化学成分,筛选到10个活性成分,成分-疾病的共同靶点84个。网络分析显示,主要活性成分为槲皮素、木犀草素、芹菜素等,关键靶点为AKT1、EGFR、SRC、ESR1、PTGS2、MMP9、KDR、MMP2、PIK3R1,并且涉及氧化-还原、负调控凋亡、蛋白质自磷酸化、ATP结合、蛋白激酶活性、蛋白丝氨酸/苏氨酸激酶活性、酶结合等过程,和癌症通路、癌症蛋白聚糖、PI3K-Akt信号通路等通路。综上,蒲公英是通过多成分、多靶点、多途径来发挥抗癌作用的。     

甘草抗动脉粥样硬化机制的网络药理学研究

利用网络药理学方法探讨甘草在抗动脉粥样硬化中的分子机制。本研究利用中医药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)分析甘草中的有效活性成分,并获得有效成分的作用靶点。通过Cytoscape软件构建可视化靶点互相作用网络,对网络中的关键靶点进行基因本体(GO)富集分析和KEGG通路富集分析。结果显示甘草中40种有效活性成分的预测靶点共97个,47个靶点与动脉粥样硬化(AS)相关,其中18个是血管保护药物和脂质修饰药物的作用靶点,表明甘草可作为调控AS发展的药物。基于97个预测靶点的GO富集分析,发现甘草可参与多种生物学过程,尤其是应对外源性刺激,以及参与细胞凋亡等过程。通过构建甘草靶点与AS疾病靶点相互作用网络(PPI),确定了AKT1、MAPK3、MAPK1、JUN和CASP3等关键靶点,并对关键靶点进行KEGG富集分析,结果表明甘草主要影响调控细胞增殖、生存以及凋亡的细胞信号转导相关通路,并激活先天免疫相关信号通路,调节炎性细胞因子释放,从而发挥抗动脉粥样硬化作用。甘草具有多成分、多靶点、多途径的作用特点,主要通过PI3K-AKT信号途径、MAPK信号途径、NOD样受体信号通路调控细胞增殖和凋亡,同时发挥免疫调控作用,从而影响动脉粥样硬化的发展,由此可见,甘草可作为动脉粥样硬化疾病治疗的候选中草药。     

Bioactive constituents and the molecular mechanism of Curcumae Rhizoma in the treatment of primary dysmenorrhea based on network pharmacology and molecular docking

BackgroundCurcumae Rhizoma (CR) has a clinical efficacy in activating blood circulation to dissipate blood stasis and has been used for the clinical treatment of qi stagnation and blood stasis (QSBS) primary dysmenorrhea for many years. However, its molecular mechanism is unknown.ObjectiveThe present study aimed to demonstrate the multicomponent, multitarget and multipathway regulatory molecular mechanisms of CR in the treatment of QSBS primary dysmenorrhea.MethodsObservations of pathological changes in uterine tissues and biochemical assays were used to confirm that a rat model was successfully established and that CR was effective in the treatment of QSBS primary dysmenorrhea. The main active components of CR in rat plasma were identified and screened by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The component-target-disease network and protein-protein interaction (PPI) network of CR were constructed by a network pharmacology approach. Then, we performed Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was adopted to verify the interactions between the core components and targets of CR to confirm the accuracy of the network pharmacology prediction results. Furthermore, we evaluated the bioactive constituents of CR and molecular mechanism of by which CR promote blood circulation and remove blood stasis via platelet tests in vivo and in vitro and Western blot analysis.ResultsThe results of HE staining and biochemical assays of PGF2α, TXB2 and Ca²⁺ showed that CR was effective in the treatment of QSBS primary dysmenorrhea. A total of 36 active components were identified in CR, and 329 common targets were obtained and used to construct the networks. Of these, 14 core components and 10 core targets of CR in the treatment of primary dysmenorrhea were identified. The GO and KEGG enrichment analyses revealed that the common targets were involved in multiple signaling pathways, including the calcium, cAMP, MAPK, and PI3K-Akt signaling pathways, as well as platelet activation, which is closely related to platelet aggregation. The molecular docking results showed that the 14 core components and 10 core targets could bind spontaneously. Two core targets (MAPK1 and CCR5) and 7 core components (Isoprocurcumenol, Curcumadione, Epiprocurcumenol, (+)-Curdione, Neocurdione, Procurcumenol, and 13-Hydroxygermacrone) were closely related to CR in the treatment of primary dysmenorrhea. Furthermore, the in vivo platelet test showed that CR clearly inhibited platelet aggregation. Five core components ((+)-Curdione, Neocurdione, Isoprocurcumenol, Curcumadione and Procurcumenol) obviously inhibited platelet aggregation in vitro. In addition, based on the relationships among the signaling pathways, we confirmed that CR can effectively inhibit the expression of MAPK and PI3K-Akt signaling pathway-related proteins and decrease the protein expression levels of ERK, JNK, MAPK, PI3K, AKT and CCR5, thereby inhibiting platelet aggregation.ConclusionThis study demonstrated the bioactive constituents and mechanisms of CR in promoting blood circulation and removing blood stasis and its multicomponent, multitarget and multipathway treatment characteristics in primary dysmenorrhea. The results provide theoretical evidence for the development and utilization of CR.