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.

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.

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。

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。

中成药联合吸入疗法治疗儿童支气管哮喘的网状Meta分析

【目的】基于网状Meta分析评价中成药联合吸入疗法对儿童支气管哮喘的疗效及安全性。【方法】计算机检索中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方医学数据库(Wanfang Data)、维普信息资源系统(VIP)、Embase、PubMed、Web of Science等数据库中收录的中成药联合吸入疗法治疗儿童支气管哮喘的临床随机对照试验,应用Stata14对数据进行网状Meta分析。【结果】最终纳入28项研究,包括7种中成药,分别为寒喘祖帕颗粒、槐杞黄颗粒、痰热清注射液、小儿肺热咳喘颗粒、喘可治注射液、玉屏风颗粒、珠贝定喘丸。网状Meta分析结果显示,在提高总有效率方面,优选概率排名曲线(surface under the cumulative ranking curve,SUCRA)的概率排序居前3位的依次为痰热清注射液联合吸入疗法、喘可治注射液联合吸入疗法、珠贝定喘丸联合吸入疗法;改善肺功能指标呼气峰值流速(peak expiratory flow,PEF)、第1秒用力呼气容积(forced expiratory volume at one second,FEV1)、FEV1与用力肺活量(forced vital capacity,FVC)的比值(FEV1/FVC)最优的干预措施分别为痰热清注射液联合吸入疗法、寒喘祖帕颗粒联合吸入疗法、珠贝定喘丸联合吸入疗法;对不良反应发生率的SUCRA概率排序的分析结果显示,小儿肺热咳喘颗粒联合吸入疗法可能为副作用最小的干预措施,珠贝定喘丸联合吸入疗法可能为副作用较大的干预措施。【结论】中成药联合吸入疗法较单纯吸入疗法可提高小儿支气管哮喘的有效率及改善肺功能指标,且安全性较好。

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。

瓜蒌皮注射液治疗稳定型心绞痛作用机制的网络药理学研究

目的探讨瓜蒌皮注射液治疗稳定型心绞痛(SAP)的作用机制。方法检索相关文献,获取制剂活性成分,采用SwissTargetPre⁃diction数据库预测其靶点。利用GeneCards数据库获取SAP疾病靶点;利用Venny 2.1平台获取共有靶点;利用MetaScape软件对作用靶点进行基因本体论(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,利用Cytoscape 3.9.1软件构建成分-靶点-通路网络,通过String数据库构建蛋白相互作用网络;通过基因表达综合(GEO)数据库获取的差异表达基因和分子对接进行验证,采用PyMOL 2.3.0软件进行可视化分析。结果共获得制剂活性成分57个,靶点517个,其中26个作用于SAP。核心活性成分为黄酮类,如木犀草素、芦丁、木犀草苷、芹菜素-7-O-β-D-葡萄糖苷和香叶木素-7-O-β-葡萄糖苷,核心靶点为TNF,FGF2,MMP-9,ICAM1,EGFR等。基因主要富集于37个GO功能(其中生物过程20个,分子功能9个,细胞组成8个)及9条KEGG通路。验证结果表明,活性成分可特异性作用于部分疾病差异表达基因。核心活性成分与靶点的结合能均小于-10.6 kcal/mol。结论瓜蒌皮注射液可能通过多种活性成分作用于多个特异性靶点,进而通过多通路发挥抗炎、抗氧化应激、抗凋亡作用,从而治疗SAP。

基于网络药理学和细胞实验探讨艾迪注射液治疗卵巢癌的机制研究

目的利用网络药理学和细胞实验探讨艾迪注射液治疗卵巢癌的关键分子靶点及可能的作用机制。方法通过中药系统药理学数据库与分析平台(Troditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库筛选艾迪注射液中中药的活性成分及作用靶点,并筛选卵巢癌异常表达的基因,取交集后获得艾迪注射液作用于卵巢癌的可能靶点。接着对可能靶点进行蛋白质互作网络分析、构建药物-化合物-靶点网络和富集分析。进一步筛选靶点,对与卵巢癌预后相关的关键基因进行实验验证,用50mg/ml艾迪注射液处理卵巢癌细胞后利用CCK-8实验观察细胞增殖能力,实时荧光定量聚合酶链反应技术检测核心靶基因的表达。结果筛选到艾迪注射液作用于卵巢癌的可能靶点共13个。这些靶点主要富集于细胞凋亡、铂耐药和白细胞介素-17等肿瘤发生、发展密切相关的信号通路。13个基因中,与卵巢癌预后相关的关键基因为细胞间紧密连接蛋白4(claudin 4,CLDN4)、分泌性白细胞蛋白酶抑制因子(secretory leukocyte peptidase inhibitor,SLPI)和杆状病毒IAP重复序列包含5(baculoviral IAP repeat containing 5,BIRC5)。细胞实验发现,艾迪注射液能显著抑制卵巢癌细胞增殖,促进卵巢癌保护性靶点BIRC5的表达,并显著下降卵巢癌危险因素CLDN4和SLPI的水平。结论艾迪注射液可能是通过影响CLDN4、SLPI、BIRC5这3个核心靶点的表达来实现多成分、多靶点、多途径的抗卵巢癌和联合化疗的增效减毒作用。

基于网络药理学研究喜炎平治疗急性支气管炎的作用机制

目的 使用网络药理学与分子对接研究喜炎平注射液治疗急性支气管炎的作用机制。方法 通过文献资料与中药系统药理数据库与分析平台(TCMSP)数据库筛选喜炎平注射液的活性成分,并结合SwissTargetPrediction预测其靶点。应用DrugBank、GeneCards和OMIM数据库筛选急性支气管炎相关靶点,合并活性成分与急性支气管炎靶点取其交集,利用String数据库构建蛋白-蛋白相互作用网络(PPI),使用Cytoscape 3.7.2软件将PPI图可视化。通过Metascape数据库对药物-疾病靶点进行GO和KEGG富集分析预测作用机制,并通过AutoDockTools平台进行分子对接验证。结果 喜炎平6个成分与急性支气管炎共34个靶点交集。作用机制涉及人T细胞白血病病毒感染、癌症通路、乙型肝炎、卡波西肉瘤相关疱疹病毒感染、EB病毒感染、人巨细胞病毒感染等。分子对接显示喜炎平治疗支气管炎的关键化合物17-氢-9-去氢穿心莲内酯-19-硫酸酯钠、17-氢-9-去氢穿心莲内酯、14-去氧-11-氧代穿心莲内酯、14-去氧-12-甲氧基穿心莲内酯、14-去氧穿心莲内酯和穿心莲内酯分别与IL6、EGFR、CXCL8、ICAM1、MMP9、MAPK8、MAPK14和ITGB2等靶点结合良好。结论 通过网络药理学与分子对接研究表明喜炎平可能通过抗病毒、调控IL-17信号通路、TNF信号通路发挥对急性支气管炎的治疗作用。

基于网络药理学与分子对接探讨喜炎平注射液防治急性肺损伤的机制

目的探讨喜炎平注射液对脂多糖(lipopolysaccharide,LPS)诱导的小鼠急性肺损伤(acute lung injury,ALI)的防治作用及机制。方法在LPS诱导的ALI小鼠模型中,通过观察肺组织病理学指标评价喜炎平注射液的防治作用;网络药理学和分子对接方法探讨其作用机制;Western blot方法验证预测的靶蛋白。结果喜炎平注射液能改善ALI小鼠肺组织病理损伤,减轻炎症反应。喜炎平注射液主要活性成分4个:14-deoxy-11-oxo-andrographolide、14-deoxyandrographolide、14-deoxy-12-methoxyandrographolide、andrographolide-19-β-D-glucoside,获得药物靶点288个,ALI相关靶点4960个,交集基因192个。喜炎平的10个核心靶点为STAT3、EGFR、PIK3R1、MAPK1、PIK3CA、NFKB1、ESR1、MAPK8、JAK2、FYN。GO富集获得BP 310个、CC 65个、MF 80个。KEGG通路富集发现ALI相关通路141条,排名前20的有MAPK、TNF-α、VEGF、cAMP、mTOR、AMPK、NOD、JAK-STAT、IL-17、NF-κB等。分子对接发现MAPK1、MAPK8、NFKB1与活性成分14-deoxy-12-methoxyandrographolide、14-deoxyandrographolide结合作用较强。Western blot发现喜炎平注射液可明显下调ALI小鼠肺部p38、JNK、ERKl/2、NF-κB p65蛋白表达。结论喜炎平注射液对ALI有一定防治作用,机制与调节MAPK和NF-κB信号通路有关。