Efficacy of Juanbi capsule on ameliorating knee osteoarthritis:a network pharmacology and experimental verification-based study

Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.

Exploring the mechanism of Bazi Bushen capsule in delaying the senescence of mesenchymal stem cells by network pharmacology method and verifying it in vitro

OBJECTIVE To explore the key mechanism of Bazi Bushen capsule(BZBS)in delaying the senescence of mesenchymal stem cells(MSCs)through network pharmacology and in vitro experiments.METHODS Network pharmacology was used to predict the mechanism targets of BZBS in delaying MSCs senescence.A MSCs senescence model induced by D-galactose(D-gal)was used to investigate the effect and mechanism of BZBS on MSCs senescence in vitro.RESULTS Network pharmacology analy⁃sis showed that BZSB could delay MSCs senes⁃cence.The experiment showed that BZBS could significantly improve the survival activity of the aged MSCs.It significantly reduced the positive rate ofβ-galactosidase staining and p16,p21 expression in aged MSCs,enhanced the ability of adipogenic differentiation and osteogenic differentiation,and increased expression of Nanog,OCT4 and SOX2 in senescent MSCs.CONCLU⁃SIONS Network pharmacology and in vitro cell experiments verified that BZBS could delay MSCs senescence.

Material Basis of Ningmitai Capsule for the Treatment of Urinary Tract Infections Based on Network Pharmacology

[Objectives]To study the main active components,targets and related pathways of Ningmitai capsule for the treatment of urinary tract infections(UTIs)based on network pharmacology.[Methods]The chemical components of Ningmitai capsule were collected through literature search,and the relevant target information of the components was sorted out.The UTIs-associated targets were also screened out using DisGeNET database and GeneCards database.Cytoscape 3.6.1 software and STRING platform were used to construct the protein-protein interaction(PPI)network,and MCODE plug-in in this software was used to analyze the action pathway and key targets of Ningmitai capsule for the treatment of UTIs.GO and KEGG pathway enrichment analysis of key targets was conducted using David database,and the component-target-pathway network diagram of Ningmitai capsule for the treatment of UTIs was established.[Results]A total of 37 active compounds,including salicylate,ferulic acid,baicalin,quercetin,apigenin and ellagic acid were screened from seven TCM components of Ningmitai capsule.There were 26 possible targets related to the treatment of UTIs,such as NFKB1,JUN,CTNNB1 and STAT3,which play an important role for the treatment of UTIs through prostate cancer,bladder cancer,pancreatic cancer and other signaling pathways.[Conclusions]The study provides a theoretical basis for the study of the mechanism of Ningmitai capsule in the treatment of UTIs.

Molecular mechanism of Compound Qingdai Capsule in the treatment of psoriasis based on network pharmacology and molecular docking

Objective:Although Compound Qingdai Capsule(CQC)successfully treats psoriasis,the exact mechanism remains unclear.Our research used network pharmacology to investigate the molecular mechanism of CQC in treating psoriasis.Methods:The Traditional Chinese Medicine Systems Pharmacology platform was used to screen the bioactive chemical elements and identify gene targets,and the ingredient-target network was visualized by Cytoscape software.Genes associated with psoriasis were found in the Gene Expression Omnibus database.The protein-protein interaction network was created using STRING and Cytoscape,and the hub genes were identified using MCODE and topological analysis.Gene ontology and Kyoto encyclopedia of genes and genomes analyses were applied to obtain hub genes’biological processes and signaling pathways.Subsequently,the ingredient-target-pathway-disease network was visualized by Cytoscape.Results:Finally,an active ingredient-target network of CQC containing 130 active ingredients and 213 targets was built.Conclusion:The top 3 bioactive components were identified as quercetin,luteolin,and kaempferol,and the top 5 hub genes were identified as IL1B,CXCL8,STAT3,MMP9,and HMOX1.The critical pathways of CQC treatment in psoriasis were AGE-RAGE signaling,IL-17 signaling,TNF signaling,Fluid shear stress and atherosclerosis,and Toll-like receptor signaling pathway.Molecular docking confirmed a robust binding affinity between the main active ingredients of CQC with the hub target proteins.On this basis,additional animal or cellular research might be undertaken to investigate the targets and mechanisms of CQC treatment in psoriasis.

Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer

BACKGROUND Although Liu-Wei-Bu-Qi capsule(LBC)inhibits tumor progression by improving the physical condition and immunity of patients with lung cancer(LC),its exact mechanism of action is unknown.AIM To through compound multi-dimensional network of chemical ingredient-targetdisease-target-protein-protein interaction(PPI)network,the principle of action of Chinese medicine prescription was explained from molecular level.METHODS Network pharmacology and molecular docking simulations were used to analyze the relationship among the main components,targets,and signaling pathways of LBC in treatment of LC.RESULTS From the analysis,360 LBC active ingredient-related targets and 908 LC-related targets were identified.PPI network analysis of the LBC and LC overlapping targets identified 16 hub genes.Kyoto Encyclopedia of Genes and Genomes analysis suggested that LBC can target the vascular endothelial growth factor signaling pathway,Toll-like receptor signaling pathway,prolactin signaling pathway,FoxO signaling pathway,PI3K-Akt signaling pathway and HIF-1 signaling pathway in the treatment of LC.Molecular docking simulations showed that quercetin had the best affinity for MAPK3,suggesting that quercetin in LBC may play an important role in the treatment of LC.CONCLUSION The results showed that the active ingredients in LBC can play a crucial role in the treatment of LC by regulating multiple signaling pathways.These results provide insights into further studies on the mechanism of action of LBC in the treatment of LC.

Study on Molecular Mechanism of Yiqing Capsule in Treating Upper Respiratory Tract Infection Based on Network Pharmacology

Objective: To investigate the possible mechanism of Yiqing Capsules in the treatment of upper respiratory tract infection based on network pharmacology. Methods: The main active components of Yiqing Capsules were selected on TCMSP database;the targets of upper respiratory tract infection were selected on GeneCards database. The drug-compound-target network and PPi network were constructed through STRING database and soft Cytoscape 3.7.2. Soft R was used to perform GO enrichment analysis and KEGG pathway enrichment analysis of main targets. Results: According to the screening conditions, 48 active compounds and 171 related targets were obtained. GO enrichment analysis obtained 2333 items, KEGG pathway enrichment analysis obtained 2248 items, including Kaposi sarcoma-associated herpesvirus infection, Human cytomegalovirus infection, Epstein-Barr virus infection, PI3K-Akt signaling pathway, etc. Conclusion: Yiqing capsules play a therapeutic role in upper respiratory tract infection through multi-target and multi-pathway.

Exploration on Shufeng Jiedu Capsule for Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking

The paper is proposed to explore the potential effects of Shufeng Jiedu Capsule against COVID-19. The ingredients and targets of Shufeng Jiedu Capsule were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the gene names of potential targets were extracted by UniProtKB. Then we did protein-protein interaction networks functional enrichment analysis by the STRING platform, reconstructed drug-target pathways and networks to predict the likely protein targets of the capsule against COVID-19 with software Cytoscape 3.6.1, and carried out GO enrichment analysis and KEGG analysis with R 5.3.2 software. At last we validated our predictions on molecular docking. The results suggested that Shufeng Jiedu Capsule contained 155 ingredients and 237 targets, including 26 main active ingredients and 45 key targets. There were 2334 biological processes (BP), 103 cell composition (CC) and 198 molecular functions (MF) in GO Enrichment Analysis, and 177 pathways in the KEGG analysis. The molecular docking analysis showed that binding energy for 26 main active ingredients ranged from -32.21 to -25.94 kJ·mol-1, and the main targets bind to SARS-CoV-2 3CL hydrolase by acting on CASP9, PRKCA, RELA and others. Our study suggested that Shufeng Jiedu Capsule has potential therapeutic effects on COVID-19.

The potential mechanism of prevention and treatment of COVID-19 by shufeng jiedu capsule was studied based on network pharmacology

Objective: To investigate the mechanism of Shufeng Jiedu Capsule(SJC) for treatment of COVID-19 based on network pharmacology. Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the active components and targets information of Polygoni Cuspidati Rhizoma Et Radix, Forsythiae Fructus, Istidis Radix, Radix Bupleuri, Herba Patriniae, Verbenae Herb, Phragmitis Rhizoma and licorice in SJC. The Genecards databases were used to obtain COVID-19 targets. The meridian tropisms of each herb in SJC were collected from ETCM Database.the proteins interations network were build by STRING database. The GO and KEGG pathways were analyzed by the computer R language. Results: SFC contains 8herbs, 176 compounds and the corresponding targets 237. 48 COVID-19 targets are treated by SJC. Such as IL-10, IL-6, PTGS1, PTGS2, GSK3B, STAT-1, IL-17 signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, T cell receptor signaling pathway and VEGF signaling pathway may be potential targets and signaling pathways for the prevention and treatment of COVID-19. Conclusion: The COVID-19 cantreatmented the potential targets and signaling pathways by the SJC, and play the role of antipyretic, anti-inflammatory, balance immunity, antiviral and so on. It will provide strong support for the later stage experiment and clinical application of SJC.

To Explore the Potential Mechanism of Yiqing Capsule in the Treatment of COVID-19 Based on Network Pharmacology

Objective: To select the ingredients and targets of Yiqing capsule in treating COVID-19 based on network pharmacology, then to explore the potential mechanism of Yiqing capsule in treating COVID-19. Methods: We screened the ingredients and targets of Yiqing capsule on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and target genes for COVID-19 in GeneCards database, constructed drug-ingredient-target network through software Cytoscape 3.7.2, and constructed protein protein interaction network (PPI) network through STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of key gene targets of Yiqing capsule are used to treat COVID-19 through software R5.3.2. Results: We got 42 ingredients, 42 potential therapeutic targets, 1643 GO items and 970 pathways in our study. The main pathway including IL-17 signaling pathway, Chagas disease (American trypanosomiasis), Influenza A, and TNF signaling pathway. Conclusion: Yiqing capsule plays a role in treating COVID-19 through multiple ingredients, multiple targets and multiple pathways.

Exploring the mechanism of Xiaopi Hewei capsule in treating functional dyspepsia based on network pharmacology

Objective:Functional dyspepsia(FD)is a widely prevalent gastrointestinal disorder throughout the world,whereas the efficacy of current treatment in the Western countries is limited.The traditional Chinese herbal formula Xiaopi Hewei capsule(XHC)is a clinically validated remedy in treating FD,but there is no literature expounds the underlying therapeutic mechanism of XHC so far.Methods:In the present study,the network pharmacology technology was used to explore the therapeutic mechanism of XHC in treating FD.We obtained relative compounds of XHC,potential targets of these compounds and FD-related targets by retrieving particular websites.Based on the matching results between XHC potential targets and disease targets,Protein-Protein Interaction(PPI)network was constructed to screen the hub targets by topology.Furthermore,DAVID bioinformatics resources were utilized for the enrichment analysis on GO and KEGG.Results:A total of 62 active compounds and 547 putative identified targets were screened from XHC,of which 241 overlapped with the targets of FD and were considered potential therapeutic targets.14 hub genes were recognized as potential targets of treatments.Moreover,the results of DAVID enrichment analysis indicated that XHC participated in the complex treating effects associated with anti-depression,inflammatory reaction and eradicating Helicobacter Pylori(HP).Molecular docking stimulation results showed that most bioactive compounds of XHC had a strong binding efficiency with hub genes.Conclusions:This study demonstrated that XHC has the characteristics of multi-compounds,multi-targets and multi-pathways in treating FD,which provides the theoretical basis for further research of XHC.

Potential mechanism of Shugan Jieyu capsule in the treatment of hepatitis B based on network pharmacology

Objective:In this study,the effective components and related targets of Shugan Jieyu Capsule(SGJY)in the treatment of hepatitis B were determined to explore the mechanism of SGJY in the treatment of hepatitis B.Methods:In this study,the effective components and targets of SGJY,and the related targets of hepatitis B were searched,and obtained the targets of SGJY in the treatment of hepatitis B according to the principle of Venn diagram.To build a protein-protein interaction network,String database was used,Cytoscape(3.7.2)software was used for topology analysis,R(4.0.5)software was used for go analysis,KEGG pathway enrichment analysis,and study of putative signaling pathways to determine how they could work.Results:SZJY was used to predict a total of 11 Chinese herbal components and 85 associated targets for the treatment of hepatitis B.34 important targets were examined,including AKT1,EGFR,and 10 important pathways were examined,including proteoglycans in cancer and the PI3K/Akt signaling pathway.Conclusion:SGJY in the treatment of hepatitis B mainly inhibits the secretion of HBsAg and HBeAg by affecting PI3K-Akt and proteoglycans in cancer,and inhibits the progression of liver cancer.

Effects of Longshengzhi Capsules(龙生蛭胶囊)on Parkinson's Disease Based on Network Pharmacology and Biological Research

Objective:To study the effects of Longshengzhi Capsules(龙生蛭胶囊,LSZC)against Parkinson’s disease based on network pharmacology and biological research.Parkinson’s disease(PD)is a kind of degenerative disease with a complex pathological process.Up to date,there is still no effective clinical treatment to cure this condition.The poor prognosis seriously affects patients’quality of life.In the case of dealing with complex pathological processes conditions,the flexible therapy strategy from traditional Chinese medicine(TCM)has unique advantages.LSZC has been clinically approved for the treatment of arteriosclerotic cerebral infarction with symptoms of paraplegia,numbness,skewed mouth,and unfavorable speech.Methods:Active ingredients of LSZC were obtained from TCM systems pharmacology(TCMSP)database,Chinese Taiwan TCM database and Sym Map database.Therapeutic targets were predicted through Pubchem and Swiss Target Prediction databases.Parkinson-related targets were collected by the Comparative Toxicogenomics Database(CTD),TTD and Drug bank databases.The overlap targets of LSZC and PD were identified for pathway enrichment analysis by utilizing Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and the Cytoscape software was used to visualize the results.Then the potential pharmacological effects of LSZC on PD were further explored by using mice model induced by MPTP.Results:LSZC showed a regulation effect on the pathological process of PD and improving the symptoms of PD model animals in vivo.And the results also showed that different drug groups have different intervention pathways for PD,suggesting that LSZC intervention on PD may be achieved through multiple channels.Conclusion:LSZC has an intervention effect on the pathological process of PD,indicating that patients with PD may benefit from LSZC usage in clinical practice.

The Mechanism of Action of Qihuang Jiangtang Capsule in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking Technology

Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine.The targets related to the active components were obtained via PubChem database.The targets related to T2DM were retrieved through the GeneCards database.The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram,and the intersecting targets were the potential targets of QHJTC in treating T2DM.The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network,and the key compounds and targets were screened by the Network Analyzer module in the Tools module.The potential targets were imported into the STRING database to obtain the interaction relationships,so as to analyze and construct the protein–protein interaction(PPI)network by Cytoscape 3.7.2 software.The intersecting targets were introduced into Metascape for gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the“active component–important target-key pathway network”for the intervention of T2DM with QHJTC.The molecular docking of active components and core targets was performed with AutoDock software.Results A total of 237 active components and 281 related targets were obtained from QHJTC,as well as 1362 T2DM targets and 155 potential targets of QHJTC in treating T2DM.There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis.There were 471 terms obtained from GO functional enrichment analysis,among which 248 related to biological processes,125 related to molecular functions,and 98 related to cellular components.There were 299 signaling pathways obtained from KEGG pathway enrichment analysis.The active components of QHJTC were found spontaneously binding to the core targets.Conclusions QHJTC can treat T2DM through multi-components,multi-targets,and multi-pathways.

Repositioning of clinically approved drug Bazi Bushen capsule for treatment of Alzheimer′s disease using network pharma⁃cology approach and in vitro experimental validation

OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar⁃get profiles of the components of BZBS were pre⁃dicted.Subsequently,new indications for BZBS were predicted by disease ontology(DO)enrich⁃ment analysis and initially validated by GO and KEGG pathway enrichment analysis.Further⁃more,the therapeutic target of BZBS acting on AD signaling pathway were identified by intersec⁃tion analysis.Two Alzheimer′s disease(AD)cell models,BV-2 and SH-SY5Y,were used to pre⁃liminarily verify the anti-AD efficacy and mecha⁃nism of BZBS in vitro.RESULTS In total,1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula,and 1320 BZBS targets with high confidence were predicted.Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treat⁃ment of AD.In vitro experiments showed that BZ⁃BS could significantly reduce the release of TNF-αand IL-6 and the expression of COX-2 and PSEN1 in Aβ25-35-induced BV-2 cells.BZBS reduced the apoptosis rate of Aβ25-35 induced SH-SY5Y cells,significantly increased mitochon⁃drial membrane potential,reduced the expres⁃sion of Caspase3 active fragment and PSEN1,and increased the expression of IDE.CONCLU⁃SIONS BZBS formula has a potential use in the treatment of AD,which is achieved through regu⁃lation of ERK1/2,NF-κB signaling pathways,and GSK-3β/β-catenin signaling pathway.Further⁃more,the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action.The study lays a foun⁃dation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.

Plasma pharmacological study on Da Huang Zhe Chong capsule on platelet aggregation of normal person

Objective To develop a plasma pharmacological method evaluates the effect of Da Huang Zhe Chong capsule on platelet aggregation and its mechanism, which is a representative Traditional Chinese Medicine Patent Prescription Promoting blood circulation by removing blood stasis. Methods Platelets specimens from healthy volunteers made serum and plasma with medicine, while platelet PRP were separated, which were divided into 8groups,i.e. auto-serum, allo-serum, serum with Da Huang Zhe Chong capsule , serum with aspirin, auto-plasma, plasma with Da Huang Zhe Chong capsule, plasma with aspirin, every group added to serum and plasma to hatch. After ADP and adrenalin were added into the specimens and hatched, the effects of specimens on platelet aggregation were observed. Results After ADP adrenalin were added, all the serum groups did not present platelet aggregation,while all the plasma group presented platelet aggregation. P1, P5, Pmax, t and TM have no significant difference (P＞0. 05) between auto-plasma group and allo-plasma group induced by ADP and adrenalin. P1, P5, t and Pmax have significant differences (P＜0. 01) and TM decreased significantly (P＜0. 05) comparing plasma group with Da Huang Zhe Chong capsule and plasma group of aspirin to allo-plasma group. P1, t and Pmax have significant difference (P＜0.05), and P5 and TM are simulate comparing plasma group with Da Huang Zhe Chong capsule to plasma group of aspirin. P1, P5, t and Pmax have significant differences (P＜0. 01), P1, TM have also significant(P＜0. 05), comparing plasma group of Da Huang Zhe Chong capsule with plasma of aspirin to allo-plasma group induced by adrenalin. P1 ,P5 and Pmax have significant differences (P＜0.05), and t and Pmax are simulate comparing plasma group with Da Huang Zhe Chong capsule with plasma group of aspirin. Conclusion The serum pharmacological study is inappropriate to study platelet aggregation in vitro. The plasma pharmacological study is inappropriate to study platelet aggregation in vitro. The plasma pharmacological study could reflect the pharmacological effect produced in vivo. Da Huang Zhe Chong capsule has better anti artery thrombosis effect than aspirin, and it is an ideal medicine for anti artery thrombosis.

Network pharmacological approach to explore the mechanisms of Lianhua Qingwen capsule in coronavirus disease 2019

Background:This study aimed to explore the molecular mechanisms of the active compounds of Lianhua Qingwen capsule in the treatment of coronavirus disease 2019 by using systemic pharmacology approach.Methods:In this study,network pharmacology methodology was applied,including active chemical component screening,target gene prediction,herbal-compound and compound-target gene network construction,gene enrichment analysis,pathway enrichment analysis and network analysis.Results:Network analysis showed that 3 bioactive ingredients(quercetin,kaempferol,AC1LIUG4)were screened as pivotal ingredients.30 target genes were identified as the anti-coronavirus disease 2019 of Lianhua Qingwen capsule.Among the targets,tumor necrosis factor,JUN(transcription factor AP-1),interleukin 6,vascular endothelial growth factor A,interleukin 1B,interleukin 2,mitogen-activated protein kinases 1 were regulated by various compounds and screened as the core genes of protein-protein interaction network.Nineteen signaling pathways screened by Kyoto Encyclopedia of Genes and Genomes pathway enrichment(P<0.05)were enriched on various inflammatory signaling pathways such as interleukin 17 signaling pathway,NF-κB signaling pathway,tumor necrosis factor signaling pathway and C-type lectin receptor signaling pathway.Conclusion:The bioactive compounds in Lianhua Qingwen capsule may have a therapeutic effect on coronavirus disease 2019 by inhibiting cytokine storms by regulating multiple inflammatory signaling pathways.

Comprehensive profiling of Lingzhihuang capsule by liquid chromatography coupled with mass spectrometry-based molecular networking and target prediction

Objective:Lingzhihuang capsule(LZHC)is a natural product that consists of 10 commonly used medicinal plants,and it is used in traditional Chinese medicine to promote people’s overall health.Previously,LZHC was successfully used as adjuvant therapy for treating patients with cancer.However,the chemical constituents of LZHC and their potential biological functions remain unclear.The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets.Methods:The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with timeof-flight mass spectrometry combined with mass spectrometry-based molecular networking.The targets were predicted using SwissTargetPrediction software,and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation,Visualization,and Integrated Discovery.The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software.Results:We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking,including triterpene(the main structural type)and other clusters(ie,flavonoids and organic acids).Our results suggested that multiple pivotal targets were regulated by LZHC,including tumor necrosis factor,nitric oxide synthase 2,glucocorticoid receptor,estrogen receptor,3-oxo-5-alpha-steroid 4-dehydrogenase 2,prostaglandin e2 receptor ep4 subtype,estrogen receptor beta,phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform,mitogen-activated protein kinase 3,and racalpha serine,which are related to signal transduction,positive regulation of transcription from RNA polymerase II promoters,oxidation-reduction processes,inflammatory responses,and other biological processes.Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC,such as cancer-related proteoglycans,the PI3K-Aktsignaling pathway,and the cAMP-signaling pathway.Conclusions:Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation,anti-aging,and tumor suppression.

基于GEO芯片和网络药理学探讨康力欣胶囊治疗乳腺癌的作用机制

目的:利用GEO芯片和网络药理学探讨康力欣胶囊治疗乳腺癌的分子机制。方法:通过TCMSP、HERB、Batman-TCM数据库检索药物的化学成分,借助Swiss Target Prediction数据库获取药物成分对应的相关靶点;在GEO数据库中检索乳腺癌的相关靶点;利用Venny 2.1.0在线软件获取药物与疾病的共同靶点;由Cytoscape 3.8.2绘制药物-成分-靶点-疾病网络;STRING数据库构建PPI网络;借助DAVID数据库进行GO功能富集和KEGG通路富集分析;运用AutoDock软件对关键的活性成分和靶点进行分子对接验证。结果:康力欣胶囊中59个有效成分通过调控106个靶点和43条通路对乳腺癌产生作用,法尼斯淝醇A、多胶阿魏素、宽叶阿魏酮、山奈酚、法尼斯淝醇B、泽兰黄醇素、槲皮素、宽叶阿魏醇、啤酒甾醇、阿魏种素等成分可以通过EGFR、JUN、PPARG、PTGS2、CCNA2、CHEK1、CDK1、CDK2、MMP9、TOP2A等关键靶点介导癌症的中枢碳代谢、细胞周期、代谢途径、癌症途径、AMPK、松弛素、FoxO、IL-17、Ras、HIF-1、MAPK、钙、胰岛素等信号通路来治疗乳腺癌。分子对接分析发现10个靶点蛋白与10个活性成分具有较好的结合能力。结论:康力欣胶囊可以通过多成分、多靶点、多途径参与乳腺癌的治疗,为其临床应用及治疗乳腺癌的机制深入研究提供了理论依据。

基于网络药理学方法和分子对接技术分析胆通胶囊治疗胆汁淤积症作用机制

目的:采用网络药理学方法和分子对接技术分析胆通胶囊治疗胆汁淤积症的作用机制。方法:使用中药系统药理数据库和分析平台(TCMSP)、本草组鉴(HERB)、PharmMapper和Uniprot数据库搜索胆通胶囊的活性成分及作用靶点。使用GeneCards数据库获取胆汁淤积症的靶点。绘制韦恩图得到药物-疾病交集靶点。利用Cytoscape 3.10.0软件构建胆通胶囊活性成分-靶点网络,得到胆通胶囊的主要活性成分。将主要活性成分、药物-疾病交集靶点通过STRING数据库与Cytoscape 3.10.0软件进行蛋白质相互作用(PPI)网络分析,得到核心靶点。利用DAVID数据库对核心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。使用PubChem数据库与PyMol、AutoDockTools软件将胆通胶囊主要活性成分与核心靶点进行分子对接。结果:共收集胆通胶囊的活性成分25个,获得疾病靶点1039个。韦恩图显示,药物-疾病的交集靶点92个。胆通胶囊活性成分-靶点网络分析结果显示,苏齐内酯、决明内酯、番泻苷E、20-殷金醇棕榈酸、(-)-儿茶素和棕榈胺A有较高的度值,为胆通胶囊的主要活性成分。PPI网络分析结果显示,白蛋白(ALB)、有丝分裂原-活化蛋白激酶1(MAPK1)、类视黄醇X受体α(RXRA)等蛋白在PPI网络中的度值较高,是核心靶点。GO功能富集分析结果显示,药物-疾病交集靶点在体内主要参与精氨酸分解代谢、尿素循环、雌激素反应等生物过程。KEGG通路富集分析结果显示,药物-疾病交集靶点在体内主要涉及精氨酸生物合成、甲状腺癌、内分泌抵抗等信号通路。分子对接结果显示,胆通胶囊的主要活性成分可对核心靶点蛋白发挥调控作用。结论:胆通胶囊通过多种活性成分作用于胆汁淤积症的多个靶点,发挥多通路治疗的作用。

基于网络药理学探讨养心定悸胶囊治疗室性心律失常的作用机制

目的:基于网络药理学探讨养心定悸胶囊治疗室性心律失常(Ventricular Arrythmia,VA)的作用机制。方法:使用中药系统药理学数据库与分析平台(TCMSP)和BATMAN-TCM等数据库筛选养心定悸胶囊的有效成分及其作用靶点,通过GeneCards、OMIM等数据库检索VA的疾病靶点,制作韦恩图,获得相关交集。使用STRING数据库制作靶点间相互作用网络,筛选关键靶点及关键成分,使用Cytoscape 3.9.1软件构建成分-靶点-通路网络。运用DAVID网站进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果:检索到活性成分146种,预测靶点761个,疾病靶点2 126个,交集靶点222个。构建的网络最终获得47个节点和708条边,获得10个核心靶点,包括重组人信号转导与转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)、丝氨酸/苏氨酸蛋白激酶1(Serine-Threonine Protein Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等。GO和KEGG富集分析与筛选显示,养心定悸胶囊治疗VA的作用通路包括磷代谢过程的正调控、细胞运动的正调控、对外源性刺激的反应等。结论:养心定悸胶囊治疗VA通过多成分、多靶点作用于磷代谢过程的正调控、对激素的反应、细胞运动的正调控等多通路发挥药效。