Efficacy of Xuebijing injection for the treatment of coronavirus disease 2019 via network pharmacology

Background:To evaluate the mechanism of Chinese patent drug Xuebijing(XBJ)injection in the treatment of a new coronavirus disease 2019(COVID-19)based on network pharmacology and molecular docking technology.Methods:The TCMSP database was employed to collect and screen the active ingredients of the Chinese herb contained in the XBJ injection.The GeneCards database and STRING database were applied to collect and expand the targets of COVID-19 and compare and screen the related targets of COVID-19 by XBJ injection.Cytoscape was employed to build a network connecting Chinese medicine,compounds,targets,disease,and topology analysis was performed via the Network Analyzer to screen the key ingredients and targets.The software of Schrödinger molecular docking was used to verify the binding activity of the key ingredients of XBJ injection and the key targets of COVID-19.Metascape platform and DAVID database were utilized to conduct Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the key targets of COVID-19 treated by XBJ injection.Results:Eight key compounds and 15 key targets were screened and verified by molecular docking;these key compounds included luteolin,quercetin,baicalein,and kaempferol.The key targets included DPP4,AR,ESR1,CALM1,and protein kinase 1.Gene Ontology analysis involved an apoptosis and hypoxia reaction and the changes in blood vessel morphology.Kyoto Encyclopedia of Genes and Genomes analysis involved signaling pathways of hypoxia inducible factor-1,VEGF,and PI3K/AKT/NF-κB.Conclusion:The mechanism of XBJ injection when used to treat COVID-19 should be further investigated as the key compounds in XBJ regulated the expression of key targets such as protein kinase 1,VEGF-A,B-cell lymphoma-2,and TNF,which affected the COVID-19 receptors such as angiotensin-converting enzyme 2 and signaling pathways like hypoxia inducible factor-1,PI3K-Akt,and NF-κB,which alleviated the inflammation,respiratory distress,and hypoxia caused by COVID-19 infection.

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.

Mechanism of Aidi injection on hepatocellular carcinoma based on network pharmacology

Objective:To explore the active ingredients and potential mechanism of Aidi injection in the treatment of hepatocellular carcinoma by network pharmacology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID)were used to screen the active ingredients of four traditional Chinese medicines of Renshen,Huangqi,Ciwujia,and Banmao and corresponding potential targets.Screening of hepatocellular carcinoma-related targets through the Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database platforms.The drug and disease targets are merged to obtain the intersection,and the information is imported into Cytoscape 3.7.2 to construct a network diagram of the active ingredients of Aidi injection and related targets of hepatocellular carcinoma,and the topology analysis is performed.A protein-protein interaction(PPI)network was constructed and analyzed using the STRING online analysis platform.Uses the Database for Annotation,Visualization and Integrated Discovery(DAVID)to perform GO function enrichment analysis of targets and enrichment of KEGG pathways analysis.Results:A total of 33 potential active ingredients were screened from Aidi injection for treating hepatocellular carcinoma,including quercetin,kaempferol,beta-sitosterol,isorhamnetin and other important active ingredients.There are 106 potential targets for active ingredient action,6,677 disease-related targets,and 89 drug-disease common targets.Through the network diagram,it was found that the highest degree of target is PTGS1.In the PPI graph,a total of 87 nodes.Among them,the higher degree values include IL6,CASP3,VEGFA,MAPK8,JUN,EGFR,MYC,PTGS2 and FOS.A total of 60 related signal pathways were obtained by GO enrichment analysis.It mainly involves biological processes such as inhibiting abnormal proliferation and differentiation of hepatocellular carcinoma cells,inhibiting angiogenesis of hepatocellular carcinoma,regulating cell cycle and promoting apoptosis.KEGG pathway enrichment analysis screened a total of eight significantly different signal pathways.Among them,P53,VEGF,MAPK,Toll-like receptor,ErbB signaling pathways play an important role in treatment.Conclusion:This study initially revealed the potential mechanism of multi-component,multi-target and multi-pathway treatment of Aidi injection for hepatocellular carcinoma,and provided ideas for the subsequent verification of the molecular mechanism of Aidi injection for hepatocellular carcinoma.

Mechanism of Xuebijing injection on hepatic ischemia-reperfusion injury based on network pharmacology

Objective:Using network pharmacology to predict the main active ingredients,targets and signaling pathways of Xuebijing injection in the treatment of hepatic ischemia-reperfusion injury and explore its potential mechanism of action.Methods:Screen the active ingredients and their targets of Danshen,Honghua,Chishao,Chuanxiong,and Danggui in Xuebijing injection through Traditional Chinese Medicine Systems Pharmacology(TCMSP)database and the Hepatic ischemia-reperfusion injury related targets through Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database.And acquire drug-disease intersection targets at the same time.The STRING database was used to construct a protein-protein interaction(PPI)network and topologically screen the central targets.Use the R language online search Bioconductor platform to perform GO function enrichment on the target;Database for Annotation,Visualization and Integrated Discovery(DAVID)database was used to perform KEGG channel enrichment analysis on the target.Use Cytoscape 3.7.2 to construct a"ingredient-target-pathway"network diagram and perform a topology analysis.Results:A total of 115 active ingredients were selected from Xuebijing injection,including Quercetin,Luteolin,Kaempferol,Beta-carotene,and Tanshinone IIa,etc.It corresponds to 217 targets.There are 1057 disease-related targets,and 114 drug-disease common targets.PPI topologically screened out 17 target proteins.Topological analysis of the network graph obtained 15 target genes.Thire intersection contains key targets such as JUN,PPARG,PTGS2,AKT1 and MAPK1.A total of 137 related signaling pathways were obtained by GO enrichment analysis.A total of 8 signaling pathways were obtained through KEGG enrichment(P<0.05,FDR<0.05),among which signaling pathways such as Toll-like receptors,T cell receptors,NOD-like receptors,VEGF,and ErbB played an important role in immune regulation,anti-apoptosis,anti-inflammatory,anti-oxidation,and promoting angiogenesis in the treatment.Conclusion:Xuebijing injection can treat hepatic ischemia-reperfusion injury through multiple components,multiple targets and multiple pathways.

Network pharmacology-based elucidation of molecular biological mechanisms of Kanglaite injection for treatment of non-small cell lung cancer

Objective: To investigate the effective compounds, potential targets and molecular mechanism of Kanglaite injection (KLTi) in the treatment of Non-Small Cell Lung Cancer (NSCLC) based on network pharmacology. Methods: The active compounds and targets of KLTi which extracted and isolated from Coix Seed were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The related genes of NSCLC were obtained by searching the Human Gene Database (GeneCards) and Online Mendelian Inheritance in Man (OMIM). The candidate targets of KLTi in the treatment of NSCLC were obtained after extracting the intersection network. The "drug-component-target-disease" network was constructed with the help of Cytoscape 3.7.2. The Protein- Protein Interaction networks were constructed on the STRING platform and core network modules were screened. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of candidate genes were performed using Metascape platform, and a "pathway-target- compounds" network was constructed to further screen key genes and active compounds. Results: A total of 11 compounds, 22 candidate targets, 206 GO functions and 12 KEGG pathways were obtained. Conclusion: The active compounds of KLTi in the treatment of NSCLC are stigmasterol, stigmasterol α1 and ergosterol. The key targets are PGR, NCOA2, PTGS2, NR3C2, and PTGS1. The core GO functions included receptor activity and binding, neuronal signal transmission and hormone stimulation;KEGG mainly involves cancer pathways, neuroactive ligand-receptor interactions and calcium signaling pathways. This study reveals the molecular biological mechanism of KLTi in the treatment of NSCLC, which is speculated to be related to neuroendocrine, providing a new basis and therapeutic direction for subsequent clinical application and experimental research.

A review on the Pharmacology and Adverse Drug Reaction of Chaihu Herbal Injection

The Chaihu herbal injection was the first herbal injection to be developed and used in China,which has been used in clinic for more than 70 years.This injection is widely used to treat fever caused by influenza or common cold and malaria.However,there is an ongoing debate about the safety of the clinical use of Chaihu herbal injection in view of the large number of adverse drug reaction reports and literature in China.On May 29,2018,the China Food and Drug Administration issued a notice requiring to revise the instruction manual of Chaihu herbal injection,list"prohibit for children"under the taboo item,and add the warning"adverse reactions of this product include anaphylactic shock".The purpose of this review is to provide updated,comprehensive information on the pharmacology and adverse drug reaction of Chaihu herbal injection based on scientific literatures in the past few decades.

Network pharmacology studies on Reduning injection in treatment of COVID-19

Background:Network pharmacology was used to explore the mechanism of the Chinese patent medicine Reduning injection in the treatment of corona virus disease 2019.Methods:The chemical constituents and targets of Qinghao(Artemisiae annuae herba),Jinyinhua(Lonicerae japonicae flos),Zhizi(Gardeniae fructus)in the Chinese patent medicine Reduning injection were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the target related to corona virus disease 2019 was searched in GeneCards database,then perform Venn analysis on the targets of corona virus disease 2019 and the Chinese patent medicine Reduning injection,to screen the compounds and targets of the Chinese patent medicine Reduning injection in the treatment of corona virus disease 2019.The String platform was used to construct the protein-protein interaction network,and key targets were screened.Cytoscape 3.5.1 was used to construct the active traditional Chinese medicine-chemical composition-target-disease network to screen the key active components,and the gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the common target through DAVID(6.8)online analysis data tool to predict the mechanism of action.Results:Fifty-two active ingredients and 232 targets were selected from the Chinese patent medicine Reduning injection,including 44 targets related to corona virus disease 2019.A total of 310 gene ontology biological processes and 94 Kyoto Encyclopedia of Genes and Genomes signaling pathways were obtained,which were mainly involved in inflammation,viral infection,bacterial infection,immune response and substance metabolism,et al.Conclusion:The mechanism of the Chinese patent medicine Reduning injection in the treatment of corona virus disease 2019 may be related to antivirus,bacteriostasis,anti-inflammatory and antifebrile,immune regulation and metabolism regulation,et al.

Network pharmacology to predicting therapy targets of traditional Chinese medicine Kang’ai injection on breast cancer

Background:To predict the effective targets of Kang’ai injection and analyze the pharmacological mechanism for the treatment of breast cancer based on the method of network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology database was used to predict the effective components of the Chinese patent medicine Kang’ai injection,and GeneCards database,Online Mendelian Inheritance in Man database and the Therapeutic Target Database were used to predict the therapeutic targets of breast cancer.Cytoscape 3.7.2 was used to construct active ingredient-disease-target network.String database and Cytoscape 3.7.2 software were used to draw the protein-protein interaction network and obtain the core target.Bioconductor and R language were used to analyze the effective action target for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results:There were 42 effective active ingredients in the Chinese patent medicine Kang’ai injection,which acted on 105 targets,and it had 32 components that acted on 96 targets associated with breast cancer.The target regulates various biological processes such as inflammation,angiogenesis,apoptosis and cell proliferation,and regulates pathways such as PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway in diabetic complications and thyroid hormone signaling pathway through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Conclusion:The treatment of breast cancer with the Chinese patent medicine Kang’ai injection is a complex mechanism process with multiple targets,multiple pathways,and multiple choices,which provides a theoretical basis for the further extraction of effective components in the treatment of breast cancer.

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.

Optimal scheme of Shengmai Injection in the treatment of angina pectoris of coronary heart disease based on Louvain algorithm: A real world study

Objective:To explore the optimal scheme of Shengmai Injection combined with other drugs for clinical doctors.Methods:Based on the large-scale data warehouse established by the institute of Clinical Basic Medicine,Chinese Academy of Traditional Chinese Medicine,the hospital information system of 22 large-scale tertiary hospitals in China was collected and 1751 patients with angina pectoris who were treated with Shengmai Injection were selected.Louvain algorithm and complex network analysis are used to build the model to summarize the rule of Shengmai Injection in the treatment of angina pectoris of coronary heart disease.Results:On the basis of Shengmai Injection,according to the symptom treatment of angina pectoris of coronary heart disease,nitrates or Suxiao Jiuxin Pill was used to dilate coronary artery;for the treatment of risk factors of angina pectoris,a combination of"insulin+acarbose+bisoprolol+nifedipine+captopril+estazolam"was used to control blood glucose and blood pressure;"Ganmao Qingre Granule+levofloxacin"to treat upper respiratory tract infection and other medication regimens were used as well.For the complications of angina pectoris of coronary heart disease,"furosemide+spironolactone+potassium chloride+magnesium sulfate"was used to reduce edema and“isosorbide nitrate+metoprolol+Shenmai injection+Wenxin Granule"was used to improve symptom of heart failure of qi and yin deficiency type.Conclusion:The therapeutic regimen of Shengmai Injection combined with traditional chinese medicine and western medicine is basically consistent with the current guidelines,but more clinical studies are still needed to explore more effective combination therapy.

Exploring the mechanism of action of DHI on myeloproliferative neoplasms based on network pharmacology

Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and relevant literature were used to search for the active ingredients and targets of Radix Salviae and Carthami Flos in DHI.Disease targets related to myeloproliferative neoplasms were obtained from the GEO database,GeneCards,and DisGeNET database.The queried component targets were normalized using the UniProt database.Potential targets were identified by constructing protein-protein interactions networks using STRING 11.5 and visualized and analyzed using Cytoscape 3.9.1.GO and KEGG analysis were performed using the Metascape platform,and visualization was done using the built-in plug-in CluoGO or SangerBox platforms with Cytoscape 3.9.1.Results:The active ingredients of DHI for treating myeloproliferative neoplasms mainly consist of flavonoids and o-benzoquinones,including quercetin,luteolin,kaempferol,stigmasterol,tanshinone iia,cryptotanshinone,beta-carotene,2-isopropyl-8-methylphenanthrene-3,4-dione,and neocryptotanshinone ii.The potential targets are JUN,TP53,STAT3,AKT1,MAPK1,RELA,TNF,MAPK14,IL6,and FOS.The relevant signaling pathways involved are mainly TNFαsignaling pathway,PI3K-Akt signaling pathway,apoptosis,IL-17 signaling pathway,cellular senescence,MAPK signaling pathway,p53 signaling pathway,JAK-STAT signaling pathway,and NF-kappa B signaling.Conclusions:DHI acts mainly through flavonoids and o-benzoquinones to treat myeloproliferative neoplasms in a multi-targeted and multi-pathway manner.

Network Pharmacology-Based Dissection of the Bioactive Compounds and Pharmacological Mechanisms of Yiqi Fumai Lyophilized Injection for the Treatment of Heart Failure

Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

Effectiveness of Shengmai Injection on angina pectoris based on real-world propensity score method

Objective:Shengmai injection is a commonly used traditional Chinese medicine for the treatment of angina pectoris.However,there is still a lack of high-quality clinical research evidence for the treatment effect of Shengmai injection for angina pectoris.Real-world studies based on large samples can provide Shengmai injection.Researches on the treatment of angina pectoris with Shengmai injection provide important evidence.Methods:This article is based on the information collected by the hospital information system(HIS)database of 22 tertiary A general hospitals for all patients who used Shengmai injection and those who did not use Shengmai injection.The propensity scoring method was used to evaluate the possible existence of the research data.The confounding factors are controlled.Through the general Logistic regression analysis method,the propensity score weighted Logistic regression analysis method and the propensity score weighted Logistic regression analysis method with covariates,the therapeutic effect of Shengmai injection on angina pectoris was explored.Results:Three kinds of logistic regression analysis showed that there were statistical differences in the treatment effect of Shengmai injection on angina pectoris in the group without Shengmai injection.Propensity score weighted logistic regression analysis with covariates balanced the effect of multiple confounding factors.Using real-world data to construct a retrospective cohort study confirmed the clinical effectiveness of Shengmai injection in the treatment of angina pectoris,and at the same time confirmed the wide application of Shengmai injection in angina pectoris complicated with multiple organ failure.Conclusion:Shengmai injection is effective in the treatment of angina pectoris.The weighted method of propensity score removes confounding factors,which improves the reliability of real-world research results.

基于网络药理学及分子对接探讨柴胡注射液退热的分子机制

目的采用网络药理学方法及分子对接研究柴胡注射液(CI)退热作用的潜在机制。方法使用中药系统药理学数据库和分析平台(TCMSP)检索、文献补充获取柴胡的活性成分、潜在靶点。借助GeneCards、DurgBank以及人类在线孟德尔遗传数据库(OMMI)数据库检索发热相关靶点。运用STRING数据库将交集靶点行蛋白质-蛋白质相互作用(PPI)分析;在Cytoscape中建立“柴胡注射液-活性成分-靶点基因-发热”的网络;利用David数据库行基因本体(GO)、京都基因与基因组百科全书(KEGG)信号通路分析;最后使用AutoDock Vina模拟分子对接。结果柴胡共有活性成分17个,作用靶点210个,发热靶点1208个,交集靶点102个。GO条目747个,涉及对外来刺激的反应、炎症反应、细胞对肿瘤坏死因子的反应、对脂多糖反应等生物学过程。KEGG通路156条,涉及AGE-RAGE、TNF、IL-17等信号通路。分子对接中成分与靶点可较好结合。结论CI通过多成分、作用于多靶点和途径对发热产生治疗作用。

生脉注射液联合局部枸橼酸钠抗凝在接受连续性肾脏替代治疗且伴有 高危出血倾向患者中的应用

目的探究生脉注射液联合局部枸橼酸钠抗凝对接受连续性肾脏替代(continuous renal replacement therapy,CRRT)治疗且伴有高危出血倾向患者降钙素原(procalcitonin,PCT)、血清白细胞介素-6(interleukin-6,IL-6)、C反应蛋白(C-reactive protein,CRP)和心肌酶谱水平的影响。方法选择行CRRT治疗并伴有高危出血倾向的患者96例,采用随机数字表法分为对照组(48例)和观察组(48例)。对照组采用局部枸橼酸钠抗凝治疗,观察组采用生脉注射液联合局部枸橼酸钠抗凝治疗,对比治疗前后2组患者急性生理学及慢性健康状况评分系统-Ⅱ(acute physiology and chronic health status scoring system-Ⅱ,APACHEⅡ)、多器官功能障碍综合征评分(multiple organ dysfunction syndrome score,MODS)、凝血功能、炎症因子(PCT、IL-6、CRP)、心肌酶谱水平及不良反应的发生情况。结果治疗前,2组患者的APACHEⅡ、MODS评分及凝血功能比较差异无统计学意义(P>0.05);治疗后,2组患者的APACHEⅡ、MODS评分明显降低,且观察组明显低于对照组(P<0.05);2组凝血酶原时间(prothrombin time,PT)、凝血酶时间(thrombin time,TT)和活化的部分凝血活酶时间(activated partial thromboplastin time,APTT)明显延长,且观察组明显短于对照组(P<0.05)。治疗后,观察组血清PCT、IL-6和CRP水平明显低于对照组(P<0.05)。治疗12、24 h后,2组患者肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)、肌酸激酶(creatine kinase,CK)水平有升高趋势,但观察组低于对照组(P<0.05)。观察组不良反应总发生率为9.71%,对照组为11.31%,2组比较差异无统计学意义(P>0.05)。结论生脉注射液联合局部枸橼酸钠抗凝可以优化接受CRRT治疗且伴有高危出血倾向患者的凝血功能,降低炎症因子水平,控制心肌损伤程度,控制病情,改善预后,且不增加不良反应发生的风险。

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益气复脉注射液治疗慢性心力衰竭的作用机制

目的:应用网络药理学探讨益气复脉注射液治疗慢性心力衰竭(CHF)的作用机制。方法:应用TCMSP、PubChem、BATMAN-TCM数据库获取药物的活性成分及靶点,运用GeneCards和OMIM数据库筛选CHF的靶点;Ven2.1.0软件筛选益气复脉注射液与CHF的交集靶点,构建药物-有效成分-关键靶点网络,使用STRING数据库构建蛋白-蛋白互作网络;通过Metascape数据库对交集靶点进行富集分析。结果:共筛选出益气复脉注射液的活性成分有人参皂苷Rh2、五味子乙素、五味子内酯E等;关键靶点包括丝裂原活化蛋白激酶3、基质金属蛋白酶9、胱天蛋白酶3等;主要包括肿瘤相关、缺氧诱导因子-1信号通路、糖尿病并发症中的AGE-RAGE信号通路等。结论:益气复脉注射液通过多成分-多靶点-多通路治疗CHF,为更加深入研究益气复脉注射液的药效物质奠定基础。

基于网络药理学和分子对接探讨瓜蒌皮注射液治疗冠心病的作用机制

[目的]通过网络药理学及分子对接的方法,探究瓜蒌皮注射液治疗冠心病的分子机制。[方法]首先通过查阅文献汇总瓜蒌皮注射液中的主要化学成分,通过中药系统药理学数据库与分析平台(TCMSP)、SwissADME数据库筛选其活性成分并预测其作用靶点,与在GeneCards数据库、OMIM数据库中获取的冠心病的相关靶点交集获得核心靶点;其次通过String数据库构建靶点蛋白互作网络,转换格式导入Cytoscape3.7.2软件构建蛋白互作网络和“相关活性成分-潜在作用靶点”网络并分析关键靶点蛋白与活性成分;然后通过Metascape数据库对靶点基因进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;最后通过AutoDock Vina软件将活性成分与核心靶点进行分子对接来对网络药理学预测的准确性进行虚拟验证。[结果]研究获得瓜蒌皮注射液治疗冠心病的可能相关活性成分10个,核心靶点7个。瓜蒌皮注射液的活性成分可能通过调控蛋白激酶B抗体(AKT1)、表皮生长因子受体(EGFR)、非受体酪氨酸激酶(SRC)、热休克蛋白90AA1(HSP90AA1)、半胱氨酸蛋白酶3(CASP3)、雌激素受体1(ESR1)、纤溶酶原(PLG)等核心靶点及丝裂原活化蛋白激酶(MAPK)、白介素(IL)-17、叉头框蛋白O(FoxO)通路等信号通路以达到治疗冠心病的作用,分子对接结果表明活性成分与关键靶点蛋白结合稳定,AKT1与3,29-二苯甲酰基栝楼仁二醇、木犀草苷和槲皮苷等对接更为稳定。[结论]瓜蒌皮注射液通过多靶点、多途径来干预冠心病,为进一步揭示瓜蒌皮注射液的药理作用机制提供理论基础。

生脉散化学成分、药理作用和临床应用研究进展及其质量标志物的预测分析

生脉散为治疗气阴两虚证的常用方,具有益气生津,敛阴止汗的功效。现代临床上生脉散常用于治疗心血管疾病和呼吸系统疾病,还有抗休克及抗肿瘤的作用。综述了近年来生脉散的化学成分、药理作用和临床应用,并基于中药质量标志物(quality marker,Q-Marker)的概念对生脉散的质量标志物进行预测分析,提出人参皂苷Rg_(1)、人参皂苷Re、人参皂苷Rb_(1)、五味子醇甲、五味子甲素、麦冬皂苷D、甲基麦冬酮A等成分可作用生脉散的质量标志物,为生脉散的质量控制以及后续的研究提供参考。

醒脑静注射液“异病同治”急性脑梗死与急性脑出血作用机制的网络药理学研究

目的:采用网络药理学探讨醒脑静注射液“异病同治”急性脑梗死(ACI)与急性脑出血(ACH)的作用机制。方法:利用中药系统药理学数据库及分析平台(TCMSP)与中医药综合数据库(TCMID)获得醒脑静注射液的有效成分及其作用靶点,同时利用人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、遗传药理学和药物基因组学数据库(PharmGkb)、治疗目标数据库(TTD)和药物靶标数据库(DrugBank)等数据库获取ACI和ACH潜在的基因靶点,在DIAGRAMS平台内绘制共同靶点韦恩图。采用Cytoscape 3.9软件构建醒脑静注射液“药物-活性成分-潜在靶点”相互作用网络图。利用STRING构建蛋白-蛋白相互作用(PPI)网络并进行拓扑分析。通过R/BioConductor对共同靶点进行基因本体(GO)及京都基因和基因组百科全书(KEGG)通路富集分析。结果:筛选共得到醒脑静注射液药物活性成分68种,对应靶点基因583个,ACI潜在靶点3 597个,ACH潜在靶点3 959个,三者共同靶点299个;PPI网络核心蛋白包括血管内皮生成因子A(VEGFA)、JUN转录因子(JUN)、信号转导与转录激活因子3(STAT3)、白细胞介素(IL)-6、肿瘤坏死因子(TNF)、清蛋白(ALB)、胱天蛋白酶3(CASP3)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、丝裂原活化蛋白激酶(MAPK)3、低氧诱导因子-1α(HIF-1α)、表皮生长因子受体(EGFR)、表皮生长因子(EGF)、前列腺素内过氧化物合酶2(PTGS2)、IL-1β、基质金属蛋白酶-9(MMP-9)等;其主要生物学通路涉及脂质与动脉粥样硬化、MAPK信号通路、流体剪切应力与动脉粥样硬化、TNF信号通路、凋亡、IL-17信号通路等。结论:醒脑静注射液通过抗氧化应激、抗炎症反应、抗细胞凋亡和促血管生成等作用机制达到“异病同治”ACI和ACH的疗效。