Network pharmacology-based approach to investigate the mechanisms of Yiyi Fuzi Baijiang Powder in the treatment of malignant tumors

目的:运用网络药理学的方法筛选中国东汉医学大家张仲景的薏苡附子败酱散的主要有效成分,预测其有效成分的作用靶点及靶点相关疾病;探讨其通过“多成分-多靶点-多通路”效应模型治疗相关疾病的作用机制。方法:通过中药化学成分数据库及文献,检索薏苡附子败酱散的化学成分,并依据TCMSP数据库的口服生物利用度和类药性指数筛选出主要有效成分。其后基于Drugbank和TCMSP数据库筛选出所有有效成分的作用靶点,利用TCMSP和TCMID数据库预测靶点相关的疾病种类,并依据国际疾病分类编码ICD-10分类。利用Cytoscape软件构建薏苡附子败酱散的主要有效成分-靶点-疾病网络图,分析其网络拓扑结构,并通过DAVID数据库对该方所涵盖的所有靶点进行生物学功能和KEGG通路进行分析。结果:本研究共筛选出薏苡附子败酱散有效成分24种,相关靶点133个,相关疾病305种,炎症、疼痛和肿瘤是其治疗的主要疾病,并可调节神经活性的配体-受体相互作用、TNF信号通路、PI3K-Akt信号通路等发挥治疗肠痈和肿瘤的作用。结论:本研究初步证实了炎症、疼痛和肿瘤是薏苡附子败酱散治疗的主要疾病,该结果不仅证实了张仲景使用薏苡附子败酱散治疗肠痈的初衷,更为该古方可能用于治疗恶性肿瘤提供科学依据。

Study on the multi-targets mechanism of YiQiFuMai powder injection on cardio-cerebral ischemic diseases based on network pharmacology

Aim YiQiFuMai Powder Injection is a well-known traditional Chinese medicine formula that has been used extensively in clinical treatment of cardio-cerebral ischemic diseases in China. However, the mechanisms under-lying its clinical efficacy remain unknown. In this study, a network pharmacology approach was employed to identify the YiQiFuMai Powder Injection＇s potential pathways and targets against cardio-cerebral ischemia. The target-path- way interaction network clustered the signaling pathways based on high degree nodes of the drug-target network. The potential protein targets presented in the highly scored clustered pathways were the key network hubs and concentrated on one or limited functional signaling pathways amenable to experimental verification. Twelve main functional annota- tion clusters and main signaling pathways for YiQiFuMai Powder Injection were established by Biocarta analysis, in- eluding the NF-KB signaling pathway, the MAPKinase signaling pathway and the mTOR-signaling pathway and so on. YiQiFuMai Powder Injection is hypothesized to target multiple proteins with a high degree and betweenness of net- work. In addition, the most related pathways were also confirmed in tumor necrosis factor-alpha （TNF-oL） induced human vascular endothelial cell line EA. hy926 by Western blot. This study elucidates the systematic network and pathway analysis of multi-targets in YiQiFuMai Powder Injection. The results provide the possible mechanisms for its mode of action against cardio-cerebral ischemic diseases and may also reveal new clues for its potential application in the inflammatory diseases or tumors.

Potential mechanism of Simiao powder in treatment of synovitis based on network pharmacology

Objective:Based on the technology and method of network pharmacology,to explore the active components and specific mechanism of Simiao powder in the treatment of synovitis.Methods:by using tcmsp database,the potential active components and related target proteins of Simiao powder were screened.Genecards and digenet database were used to predict the target of synovitis.UniProt database was used to query the corresponding gene names.The compound synovitis target network and protein of Simiao powder were constructed by using Cytoscape and string software In R language,bio conductor data package was used to analyze the enrichment of go biological function and KEGG pathway,and the effective components and targets of Simiao powder in the treatment of synovitis were obtained.Results:64 key active components of Simiao powder were screened out from tcmsp database,71 of them were involved in the interaction of main chemical components of Simiao powder-chemical components and synovitis treatment target-synovitis.95 PPI core genes were obtained,and 90 go biological enrichment processes were obtained by go enrichment analysis.The results of network pharmacology indicate that Simiaosan can regulate 32 signaling pathways in the treatment of synovitis,including IL-17 signaling pathway,TNF signaling pathway,T cell receptor signaling pathway and toll like receptor signaling pathway.Conclusion:the treatment of synovitis with Simiao powder is a complex process of multi-component,multi-target and multi-channel,which is related to the coordinated regulation of multiple targets and signal pathways.

Study on the mechanism of Shenling Baizhu Powder in the treatment of diarrhea-type irritable bowel syndrome based on network pharmacology and molecular docking

Objective:Explore the possible intervention mechanism of Shenling Baizhu Powder on IBS-D from network data through network pharmacology and molecular docking simulation technology.Methods:Establish a complete regulatory network of Shenling Baizhu powder on IBS-D after obtaining the active components and drug targets of Shenling Baizhu Powder on the TCMSP platform and obtaining the disease targets of IBS-D from GeneCards and OMIM databases.Then screen out the potential best target of Shenling Baizhu Powder in IBS-D intervention network combining with the PPI network constructed in the STRING database,and screen the potential core of compounds through the molecular docking simulation and comparison with pivecurium bromide.After that,the related gene ontology functions and pathways of Shenling Baizhu Powder in treating IBS-D will be obtained though gene ontology(GO)enrichment analysis through DAVID database and Kyoto encyclo-pedia of genes and genomes(KEGG)pathways enrichment analysis through Bioconductor database.Results:The number of IBS-D disease-related targets was 2,724.And there were 184 active compounds in Shenling Baizhusan,among which 175 could act on IBS-D.After screening,four potential best targets of PTGS2,ESR1,AR and MAPK14 were obtained,and four core compounds of quercetin,luteolin,kaempferol and isorhamnetin were obtained by molecular docking simulation.GO enrichment analysis results showed that there were 92 biological processes,18 cellular components and 21 molecular functions associated with shenling Baizhu Powder intervention IBS-D process.The results of KEGG pathway enrichment analysis showed that shenling Baizhu Powder had 172 pathways involved in the intervention of IBS-D.Conclusion:The intervention effect of Shenling Baizhu powder on IBS-D was better than pivecurium bromide in terms of the number of targets and the ease of binding to the targets.Its intervention process of IBS-D may be closely related to inflammation,cancer,endocrine disorders and other related reactions and pathways,among which quercetin,luteolin,kaempferol and isorrine are the most potential core compounds in the intervention network,and the four target proteins of PTGS2,ESR1,AR and MAPK14 are the potential best target options in the intervention network.

Study on the mechanism of Yupingfeng Powder in the treatment of non-small cell lung cancer based on network pharmacology and molecular docking method

Objective:The mechanism of Yupingfeng Powder in the treatment of non-small cell lung cancer was analyzed by network pharmacology and molecular docking method.Methods:Search the related literature and TCMSP database,query the chemical composition and action target of Yupingfeng powder,query the disease database of Genecards,OMIM,DisGeNET,Drugbank,etc.,use"non-small cell lung cancer"as the keyword to search the disease-related target,select the intersection target with Yupingfeng powder as the research target,and use Cytoscape 3.7.2 software to construct the active component-target network map.The protein-protein interaction network map was constructed by using STRING database,and the treatment core targets were further screened by topological parameters,and GO analysis and KEGG signal pathway enrichment analysis were carried out.Finally,molecular docking was verified.Results:37 active components of Yupingfeng Powder were screened,including 146 common targets and 44 core targets.GO analysis and KEGG analysis show that the core target participates in many biological processes such as angiogenesis and cell proliferation,and acts on a variety of signal pathways such as AGE-RAGE,IL-17,TNF,MAPK and so on.Molecular docking shows that the core compound has good docking activity with the target.Conclusion:Network pharmacological analysis shows that Yupingfeng powder in the treatment of non-small cell lung cancer involves multi-target and multi-pathway mechanism,and the drug and target have good docking activity,which can provide theoretical basis for follow-up experimental research.

A network pharmacology analysis on Jiawei Buhuanjin Zhengqi powder against COVID-19 in children

Background:To clarify the effectiveness and potential mechanism of Jiawei Buhuanjin Zhengqi powder(JBZP)for the prevention and treatment of coronavirus disease 2019(COVID-19)in children based on network pharmacology.Methods:The active ingredients and action targets of Jiawei Buhuanjin Zhengqi powder formulas were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Genes related to COVID-19 were found on the GeneCards database.The active ingredients-target network map was constructed by Cytoscape.The action mechanisms of these genes were predicted using a Gene Ontology-based functional enrichment and annotation tool and the Kyoto Encyclopedia of Genes and Genomes.Results:Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,187 eligible compounds and 12,921 targets of Jiawei Buhuanjin Zhengqi powder were identified.A total of 257 genes related to Jiawei Buhuanjin Zhengqi powder and 401 genes related to COVID-19 in children were screened and 59 common target genes were obtained.The network analysis showed that the predicted seven main active components were Quercetin,Luteolin,Wogonin,Kaempferol,Irisolidone,Nobiletin and Licochalcone a.Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that key targets were associated with regulating immunological function or glycosylation through the biological processes.Conclusion:The potential mechanisms of Jiawei Buhuanjin Zhengqi powder on COVID-19 in children might be related to anti-inflammatory,virus infection,and immunomodulatory signaling pathway.

Discussion on the mechanism of Xiaoyao Powder in the treatment of irritable bowel syndrome based on network pharmacology

Objective:To predict the key components and potential targets of Xiaoyao Powder in the treatment of irritable bowel syndrome(IBS)and explore its mechanism of action in the treatment of IBS.Methods:The active components and related targets of all compounds of Xiaoyao Powder were obtained by systematic Pharmacological Analysis platform of traditional Chinese Medicine(TCMSP).The related genes of IBS were collected by Genecards and TTD.The network model of"Xiaoyao powder-compound-target-IBS"was established by Cytoscape software.STRING and Metascape platforms were used to analyze drug-disease target protein interactions and conduct network construction and module analysis.Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the targets.Results:In the end,149 active ingredients,267 potential targets were obtained in Xiaoyao Powder and 1751 IBS-related targets were obtained from the platforms.One hundred and sixty-five related targets were involved in the treatment of IBS by Xiaoyao Powder,among which the key targets were MMP9,VEGFA,EGF,and IL-1B,TNF,IL-6.In the GO function enrichment analysis,1976 entries were obtained for biological processes,210 entries for molecular functions,and 122 entries for cellular components;KEGG pathway enrichment analysis was performed to obtain PI3K-Akt pathway,AGE-RAGE signaling pathway,Calcium signaling pathway.Conclusion:Xiaoyao Powder may treat IBS by strengthening intestinal barrier function,reducing visceral sensitivity,inhibiting oxidative stress and inflammation.

Mechanism of Yiyi Fuzi Baijiang powder in treatment of ulcerative colitis on network pharmacology and m olecular docking

Objective:To explore the mechanism of Yiyi Fuzi Baijiang p owder in treatment of ulcerative colitis in Coix Lacryma-jobi based on network pharmacology and molecular docking technology.Methods:Search for Yiyi Fuzi Baijiang powder’s active ingredient by traditional Chinese medicine database and analysis platform system pharmacology,Genecards,Uniprot database and Cytoscape software were used to construct the active component-ulcerative colitis disease target network,and gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed,Autodock Vina was used for molecular docking verification.Results:Quercetin,luteolin,kaempferol,chrysin,macroanol B,β-sitosterol,stigmasterol,deltoan and rhizoctonine may play a role in the treatment of ulcerative colitis.KEGG pathway enrichment analysis showed that Yiyi Fuzi Baijiang p owder mainly involved i nterleukin-17 signaling pathway and cancer pathway,among which the key targets were PTGS2,HSP90AA1 and CASP3 and had a good binding activity with 10 main active components.Conclusion:The treatment of ulcerative colitis by Yiyi Fuzi Baijiang p owder may be mainly through quercetin,luteolin,macroanol B,β-sitosterol and other chemical components involved in cancer pathway,i nterleukin-17 signaling pathway acting on PTGS2,HSP90AA1,CASP3 and other disease targets in response to inorganic substances,response to cytokines and other biological processes f actor receptor binding and other molecular functions to achieve the purpose of treating u lcerative colitis.

Research Progress on Material Basis,Pharmacological Effect and Clinical Application of Danggui Shaoyao Powder

The research of modern pharmacology displays that main material basis of Danggui Shaoyao Powder exerting efficacy includes ligustilide,paeoniflorin,poria acid,ferulic acid,ligustrazine and so on,and its efficacy is mainly realized by regulating neural receptor-ligand interaction,cytokine release,and TNF-αinflammatory pathway.Systematic study of metabonomics,serum pharmacochemistry and network pharmacology of Danggui Shaoyao Powder sufficiently clarifies its potential pharmacodynamic mechanism,and it could provide scientific theoretical basis for its clinical application.In this paper,by systemically analyzing material basis of Danggui Shaoyao Powder,and exploring its complex pharmacological mechanism and clinical application in vivo,it could comprehensively understand the clinical value of Danggui Shaoyao Powder,so as to provide beneficial reference for further development of the material basis,quality control and classical prescription of Danggui Shaoyao Powder.

Observation on Therapeutic Effects of Shengmai Powder (生脉散)in Treating Acute Viral Myocarditis

Objective: To evaluate the clinical efficacy of Shengmai Powder (SMP, 生脉散) in treating a-cute viral myocarditis objectively. Methods: One hundred and twenty-four patients with acute viral myocarditis were randomized into the treated group (SMG, n = 64) and the control group(CG, n = 60 ). Such myo-cardial nutrient medicine as ATP, CoA , Vit-C, were given to both groups. And to the treated group, 40 ml of Shengmai Injection per day was given intravenously for 2 weeks, which was followed by oral intake of Shengmai granule, one package three times daily for another 2 weeks in total. The same anti-arrhythmia agents were applied to both groups, and no fructose-1, 6-diphosphate (FDP) for either. Semi-quantitative scoring method was adopted to observe such symptoms as chest stuffiness, palpitation and chest pain before treatment and four weeks after treatment. Meanwhile, EGG, dynamic ECG by Holter monitor, left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), serum neutralizing antibody of virus Coxsackie B, cardiac troponin I (cTnl) and cardiac troponin T (cTnT) were examined. Results: (1) Compared with the control group, more significant improvement was got in SMG in respects of chest stuffiness, palpitation, chest pain and arrhythmia (P<0.05 or P<0.01). (2) Negative converting rates of cTnl ,cTnT in the two groups were 59.46% vs35.48%, 68.75% vs42.31% respectively ( P<0. 05). (3) LVEDD before and after treatment in SMG was 52. 44 ± 3. 40 mm and 48. 81 ± 2. 23mm respectively, while that in the control group was 52. 31 ± 3. 74 mm and 49. 92 ± 2. 67mm respectively; LVEF before and after treatment in SMG was 60.67 ± 4. 62 % and 65. 02 ± 4. 16 % respectively, while that in the control group was 60.91 ± 4. 26 % and 63. 67 ± 3.17 % . There was obvious improvement in the two parameters in both groups, but the improvement in SMG was superior to that in the control group ( P<0. 05). Conclusion: SMP shows a good effect in improving clinical symptoms and signs, heart function, abnormal ECG and inflammatory injury indexes in patients with acute viral myocarditis.

Network pharmacological analysis on the active ingredients of Yigan Powder in treating Alzheimer's disease with depressive disorder

Objective:To study the potential therapeutic effect of Yigan Powder on Alzheimer’s disease(AD)comorbid Depressive Disorder with Network Pharmacology.Methods:The active ingredients of Yigan Powder were screened from Traditional Chinese Medicine Systems Pharmacology database and analysis platform(TCMSP)by ADME parameters,targets are predicted by Swiss Target Prediction database,disease targets are downloaded from GeneCards,OMIM and PharGKB database.Using R to run GO terms enrichment and KEGG pathway enrichment analysis.Protein interaction data is downloaded from the String database.Cytoscape software is used to build network.AutoDock Vina and PyMOL software are used for molecular docking.Results:There are 125 active ingredients in Yigan Powder with 953 predicted targets,85 of predicted targets are related to Alzheimer's Disease comorbid Depressive Disorder,shows highly enriched signaling pathways and biological processes.PPI network shows APP,MAPK1 and STAT3 may be important potential treatment of Alzheimer's Disease comorbid Depressive Disorder.The results of AutoDock Vina docking showed that the active ingredients of Yigan Powder had good binding activity with important receptors.Conclusion:Yigan Powder shows effect on neurotransmitter metabolism,synaptic transmission,neuroinflammation and other aspects in the treatment of Alzheimer's Disease comorbid Depressive Disorder.

Study on Anti-tumor Mechanism of Poria cocos Based on Network Pharmacology

Background:This paper investigates the anti-tumor mechanism of action of Poria cocos on the basis of network pharmacology.Method:In this paper,we screen the potential active ingredients of Poria cocos by TCMSP and obtain their corresponding targets with SwissTargetPrediction.The GeneCards and OMIM databases are used to screen the relevant pathogenic candidate targets in various tumor disease processes.Furthermore,we obtain Poria cocos-tumor common targets by taking the intersection of Poria cocos potential targets and candidate target groups.Subsequently,the protein-protein interaction network(PPI)of common target genes is mapped based on the STRING database,and the"drug-active component-target gene-disease"network is constructed with the help of Cytoscape3.7.2.Therefore,the core target genes are obtained.Finally,GO and pathway enrichment analysis of the core target genes are performed by Metascape and DAVID.Results:38 common targets and 7 core genes(ESR1,MAPK3,MAPK8,MTOR,PIK3CA,JAK2,and IL6)in Poria cocos-tumors are found.They play an anti-tumor role by regulating various classical pathways such as PI3K-Akt signaling pathway,mTOR signaling pathway,Prolactin signaling pathway,ErbB signaling pathway,Choline metabolism in cancer.Conclusion:The research reveals the effective anti-tumor function of Poria as a multi-component,multi-target and multi-pathway herbal medicine.

基于豚鼠模型结合网络药理学探究七白粉的皮肤美白作用机制

目的:研究七白粉的皮肤美白作用,并结合网络药理学和分子对接技术预测其达到美白效果的作用机制。方法:采用紫外线B波段(UVB)照射诱导豚鼠皮肤色素沉着,建立动物模型。观察七白粉对模型豚鼠的美白效果,同时检测黑色素细胞数和超氧化物歧化酶(SOD)、丙二醛(MDA)、酪氨酸酶(TYR)及脂褐质(LF)等与皮肤色素沉积相关的生化指标。利用网络药理学预测七白粉美白的作用机制,并通过分子对接和表面等离子体共振(SPR)进行验证。结果:在动物实验中,与模型组比较,七白粉可显著改善皮肤亮度,且黑色素细胞数和TYR、LF、MDA水平均显著降低,而SOD水平显著升高。网络药理学研究发现七白粉通过儿茶素没食子酸酯、茯苓酸C、别欧前胡素等关键成分,作用于蛋白激酶Bα(AKT1)、肿瘤坏死因子(TNF)、表皮生长因子(EGFR)等关键靶标,调控磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-AKT)和TNF等信号通路改善黑色素沉积而发挥美白作用。分子对接和SPR结果显示关键成分与关键靶标有较好的亲和力。结论:七白粉可通过抗氧化和抑制TYR的活性达到美白皮肤的效果。此外,七白粉通过多成分作用于多靶点,调控多通路改善黑色素沉积而发挥美白作用,体现了中药复方君臣佐使相互协同,多成分,多靶点,多通路的特点。

柴胡疏肝散治疗非酒精性脂肪肝的网络药理学机制

目的基于网络药理学探究柴胡疏肝散治疗非酒精性脂肪肝(NAFLD)的作用机制。方法检索TCMSP数据库获取柴胡疏肝散活性成分及靶标,通过Gene Cards获取NAFLD相关靶标,随后利用Omicshare数据库获取药物及疾病的交集靶标并进行富集分析。借用STRING数据库对交集靶标构建PPI。利用cytoscape软件分析所得网络图,得到柴胡疏肝散治疗NAFLD的关键化合物及关键靶标。结果筛得柴胡疏肝散治疗NAFLD关键化合物4个,关键靶标包括蛋白激酶(AKT1)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)和血管内皮生长因子A(VEGFA),涉及AGE-RAGE、NAFLD、核因子-κB(NF-κB)等信号通路。结论柴胡疏肝散通过多成分激活AGE-RAGE和NAFLD等信号通路治疗NAFLD,为临床应用提供理论新依据。

基于网络药理学和生物信息学探讨生脉饮(党参方)治疗慢性心力衰竭的作用机制

目的:运用网络药理学和生物信息学方法,探究生脉饮(党参方)治疗慢性心力衰竭(CHF)的活性成分、作用靶点和分子通路,阐明生脉饮(党参方)治疗CHF的分子机制。方法:借助中药系统药理学数据库与分析平台(TCMSP)以及BATMAN-TCM平台获取生脉饮(党参方)有效活性成分及化合物潜在靶点,检索GeneCards、治疗靶点数据库(TTD)、DrugBank、DisGeNET数据库,筛选CHF相关靶点;将化合物与疾病交集靶点通过STRING数据库构建蛋白相互作用(PPI)网络图,采用Cytoscape软件获得生脉饮(党参方)作用于CHF的关键化合物和核心靶点,使用R语言软件包进行基因本体(GO)生物学过程分析和京都基因与基因组百科全书(KEGG)通路分析并可视化,在基因表达综合数据库(GEO)下载CHF基因表达芯片,经过R语言软件包处理后验证核心靶点基因差异表达情况,最后,使用Autodock软件将有效成分和核心靶点进行分子对接再次验证,并将结果可视化展示。结果:共筛选得到35个有效化学成分、120个潜在靶点,获得菠菜甾醇、11-羟基兰金断肠草碱、α菠菜甾醇、邻苯二甲酸二异辛酯、黄豆黄素、去氧哈林通碱等有效成分,丝氨酸/苏氨酸激酶(AKT1)、非受体酪氨酸激酶(SRC)、表皮生长因子受体(EGFR)等核心靶点,关键通路包括氧化应激、酪氨酸磷酸化修饰、磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/AKT)等。GEO芯片验证结果显示核心靶点在健康组与疾病组之间差异表达明显。分子对接结果显示生脉饮(党参方)关键有效成分与核心靶点整体结合较好。结论:生脉饮(党参方)可能通过AKT1、SRC、EGFR、热休克蛋白(HSP90AA1)、前列腺素内过氧化物合酶2(PTGS2)、基质金属蛋白酶9(MMP-9)等多靶点和PI3K/AKT信号通路改善心肌重塑、抑制细胞凋亡、调节雌激素、抗脂质及动脉粥样硬化等作用改善CHF。

基于网络药理学探讨加味当归芍药散对子宫内膜异位症痛经的作用机制及实验验证

目的:基于网络药理学探讨加味当归芍药散治疗子宫内膜异位症(EMs)痛经的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)、人类孟德尔遗传在线数据库(OMIM)、人类基因数据库(GeneCards)、人类疾病相关基因与突变位点信息数据库(DisGeNET)、疗效靶点数据库(TTD)等数据库分析组方活性成分及潜在作用靶点,构建加味当归芍药散活性成分-EMs痛经靶点网络,并对核心靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)通路富集分析,应用分子对接vina(Autodock vina)软件对组方潜在活性成分及核心靶点进行分子对接,并采用实时荧光定量逆转录聚合酶链反应(RT-qPCR)及蛋白免疫印记法初步验证组方对EMs小鼠模型子宫内膜预测靶点mRNA及相关蛋白表达的影响。结果:组方筛选出活性成分86个,其治疗EMs痛经对应的交集靶点共64个,其中度值较高的靶点包括表皮生长因子受体(EGFR)、肿瘤抑制基因p53(TP53)、前列腺素内过氧化物合酶2(PTGS2)、血管内皮生长因子A(VEGFA)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、白细胞介素6(IL-6)、基序趋化因子配体8(CXCL8)、基质金属蛋白酶9(MMP9)等。GO功能富集分析共得到1990个条目,KEGG通路分析涉及雌激素、黏着斑等127条通络。分子对接结果显示,组方核心成分槲皮素与VEGFA、AKT1、低氧诱导因子1A(HIF1A)等关键靶点具有良好的结合力。验证实验显示,加味当归芍药散可显著下调EMs小鼠模型VEGFA、CXCL8、TP53等mRNA及MMP9、环氧合酶-2(COX-2)蛋白表达水平。结论:加味当归芍药散的核心成分可调控EMs痛经的多个靶点,其作用机制可能和调控细胞侵袭、雌激素、免疫、炎症反应等信号通路相关。

基于网络药理学探讨栀黄止痛散治疗类风湿性关节炎作用机制及实验验证

目的结合网络药理学及体外细胞实验探索栀黄止痛散(Zhi-Huang-Zhi-Tong powder,ZHZTP)治疗类风湿性关节炎(rheumatoid arthritis,RA)的有效物质基础及相关作用机制。方法使用数据库检索并筛选得到ZHZTP活性成分靶点和疾病靶点;交集得到共同靶点;构建“药物-成分-靶点”关系网络图对交集基因进行GO和KEGG富集分析;并将核心成分与核心靶点进行分子对接。最后基于HUVEC细胞体外炎症模型,采用MTT法、平板划痕实验及蛋白质印迹等方法验证ZHZTP的药效及机制。结果ZHZTP中筛选出核心成分熊果酸和大黄素;治疗RA的重要靶点AKT1、IL-6和TNF;富集分析中,GO结果表明,ZHZTP对细胞分子功能、生物学功能及细胞组成均有影响,KEGG结果表明,ZHZTP的功能主要富集在PI3K-AKT、TNF和IL-17信号通路;分子对接结果显示,核心成分与核心靶点具有较好结合作用。体外结果表明,不同浓度的ZHZTP均可抑制HUVECs的炎性增殖和迁移,并且能够抑制PI3K,AKT及m-TOR蛋白表达水平。结论ZHZTP可能通过PI3K/AKT/m-TOR信号通路调控RA疾病发展进程,从而发挥抗RA作用,其主要有效物质基础为熊果酸和大黄素。

生脉散合杏苏二陈方辅助西医基础治疗气阴两虚兼痰浊证急性加重期慢性阻塞性肺疾病患者的临床观察

目的 探讨生脉散合杏苏二陈方辅助西医基础治疗气阴两虚兼痰浊证急性加重期慢性阻塞性肺疾病(Acute exacerbation of chronic obstructive pulmonary disease,AECOPD)患者的临床疗效。方法 选取2020年3月—2022年3月期间六安市中医院收治的气阴两虚兼痰浊AECOPD患者80例,按照随机数字表法分为对照组和研究组,每组各40例。对照组采用常规西医基础疗法,研究组在对照组基础上联合生脉散合杏苏二陈汤。治疗1个月后,观察比较两组患者临床疗效,治疗前后中医证候评分、动脉血气指标[血氧饱和度(Oxygen saturation,SaO_(2))、动脉血氧分压(Partial pressure of oxygen,PaO_(2))、动脉血二氧化碳分压(Arterial carbon dioxide partial pressure,PaO_(2))]、炎症相关指标[白细胞介素-6(Interleukin-6,IL-6)、C反应蛋白(C-reactive protein,CRP)、降钙素原(Procalcitonin,PCT)]及肺通气功能相关指标[第1秒用力呼气容积(Forced expiratory volume in one second,FEV_(1))、用力肺活量(Forced Vital Capacity,FVC)、一秒率(Forced expiratory volume in one second/Forced Vital Capacity,FEV_(1)/FVC)]表达水平。结果 治疗后两组患者咳嗽、咳痰、喘息、发热、食欲下降、大便干结评分均较治疗前降低,差异有统计学意义(P<0.05);且研究组咳嗽、咳痰、喘息、发热、食欲下降、大便干结评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者SaO_(2)、PaO_(2)指标均较治疗前升高,PaCO_(2)指标均较治疗前降低,差异有统计学意义(P<0.05);且研究组SaO_(2)、PaO_(2)指标均较对照组明显升高,PaCO_(2)指标较对照组明显降低,差异有统计学意义(P<0.05)。治疗后两组患者炎症指标IL-6、CRP、PCT表达水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组炎症指标IL-6、CRP、PCT表达水平均较对照组明显降低,差异有统计学意义(P<0.05)。治疗后两组患者FEV_(1)、FVC、FEV_(1)/FVC值均较治疗前明显升高,差异有统计学意义(P<0.05);且研究组FEV_(1)、FVC、FEV_(1)/FVC值均明显高于对照组,差异有统计学意义(P<0.05)。治疗后研究组临床总有效率92.50%(37/40)明显高于对照组75.00%(30/40),差异有统计学意义(P<0.05)。结论 生脉散合杏苏二陈汤通过改善气阴两虚兼痰浊证AECOPD患者的肺通气功能,同时还可调节机体免疫炎症反应,从而提高整体治疗效果。

基于网络药理学研究丹栀逍遥散治疗便秘的作用机制

目的基于网络药理学研究丹栀逍遥散治疗便秘的作用机制。方法利用TCMSP、BATMAN-TCM、Uniprot、GeneCards等数据库检索筛选丹栀逍遥散关键成分及相关靶点、疾病靶点和相关通路。通过STRING数据库和Cytoscape软件绘制PPI网络图,寻找核心基因。利用Metascape和BioGPS数据库通过微生信平台进行基因富集分析。利用SwissDock平台进行分子对接分析。结果丹栀逍遥散药物靶点746个,便秘靶点1620个。关键靶点为VEGFA、CASP3、TNF、JUN,关键成分为槲皮素、β-谷甾醇、山奈酚、豆甾醇。关键靶点主要作用于淋巴细胞、平滑肌、结肠、结直肠腺癌、小肠,主要富集于炎性肠病、NF-κB信号通路等。分子对接结果显示活性成分与靶点蛋白结合稳定。结论丹栀逍遥散治疗便秘的作用机制,可能是通过其4个关键成分作用于4个关键靶点,调节多通路,起到抑制炎症、保护肠黏膜屏障、调节肠道菌群等作用。

基于Meta和网络药理学分析参苓白术散治疗糖尿病肥胖的作用机制

目的:采用文献荟萃分析法(Meta)评估参苓白术散对糖尿病型肥胖的治疗作用,再结合网络药理学和动物实验方法分析参苓白术散治疗糖尿病肥胖的作用机制。方法:纳入国内外相关文献,以身体质量指数(BMI)、糖化血红蛋白(HbA1c)、餐后2 h血糖(2 h PG)、空腹血糖(FBG)、胰岛素抵抗指数(Homa-IR)、腰臀比作为结局指标,评估参苓白术散对糖尿病型肥胖的治疗作用。从GEO数据库中下载糖尿病肥胖的相关基因,在中药系统药理学数据库与分析平台(TCMSP)、中医药综合数据库(TCMID)和中药分子机制生物信息学分析工具(BATMAN-TCM)中下载参苓白术散的作用靶点,对两者的交集靶点进行蛋白质-蛋白质相互作用分析,再根据拓扑分析筛选出核心靶点蛋白质;制备糖尿病肥胖小鼠的模型,分组后进行参苓白术散的灌胃治疗,2周后测量各组小鼠体质量、血糖、Lee's指数,采用苏木精-伊红(HE)染色法分析各组小鼠的脂肪细胞体积变化,测量小鼠血清中的胆固醇、三酰甘油及核心靶点蛋白质的浓度。结果:共纳入9篇文献,数据完整,未发现发表偏倚,评估为low risk。患者服用参苓白术散后,BMI、HbA1c、2 h PG、Homa-IR和腰臀比均得到明显改善;参苓白术散-糖尿病肥胖的交集靶点共59个,核心靶点为载脂蛋白E(APO-E)、胰岛素生长因子-1(IGF-1)、纤溶酶原激活物抑制物-1(PAI-1),参苓白术散主要通过影响细胞对油酸的反应(GO:0071400)、转化生长因子β1生产的正调控(GO:0032914)和纤溶酶原激活的负调控(GO:0010757)等生物学功能,影响不饱和脂肪酸的生物合成(hsa01040)、脂肪酸代谢(hsa01212)等信号通路来治疗糖尿病肥胖;动物实验结果表明,经过参苓白术散灌胃治疗后的小鼠血糖变化不显著,体质量和Lee's指数呈现明显下降趋势,脂肪细胞直径明显缩小,胆固醇、三酰甘油浓度及APO-E、IGF-1、PAI-1水平均呈现下调趋势。结论:结合Meta分析和动物实验的结果,参苓白术散对糖尿病肥胖具有明显的治疗作用,其作用机制可能与影响不饱和脂肪酸、脂肪酸的合成,减少糖和脂肪的转化,纠正机体能量代谢失衡,调控自噬促进脂肪组织的分解有关。