Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia

Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

Analyzing the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells

Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.

Metabolomics and network pharmacology reveal the mechanism of the Jiawei Yangshen pill in treatment of cyclophosphamide-induced dyszoospermia in mice

Background:The Jiawei Yangshen pill enhances sperm abundance.However,the pharmacological mechanism of action of the Jiawei Yangshen pill remains unclear.This study aimed to explore the therapeutic effect of the Jiawei Yangshen pill in the treatment of dyszoospermia and study the underlying mechanism.Methods:A dyszoospermia model was established by injecting mice with cyclophosphamide(50 mg/kg)consecutively for 7 days.Physiological and pathological indicators of the testis and hormone levels were examined after 4 weeks of treatment.Untargeted metabolomics using high-performance liquid chromatograph-mass spectrometry was performed on testis specimens.Network pharmacology analysis was used to construct an“ingredient-target-disease”interactive network,followed by metabolic pathway enrichment analysis.Western blotting was performed to examine the levels of the related proteins.Results:The Jiawei Yangshen pill significantly increased the testis index,epididymal index,sperm count,and testosterone level,while concurrently decreasing sperm mortality and luteinizing hormone levels.The spermatogenic cells in the Jiawei Yangshen pill-treated mice were well arranged with an increased number.Significantly different metabolites were identified.Western blotting showed that the expression levels of p-anti-adenosine monophosphate-activated protein kinase/anti-adenosine monophosphate-activated protein kinase and p-protein kinase B/protein kinase B were significantly increased after the Jiawei Yangshen pill treatment,whereas the expression levels of transforming growth factor-β1 and nuclear factor kappa B(p65)were remarkably decreased.Conclusion:The Jiawei Yangshen pill significantly improved testicular microcirculatory injury and overall metabolic levels in mice with dyszoospermia.

Molecular targets and mechanisms of Jiawei Jiaotai Pill on diabetic cardiomyopathy based on network pharmacology

BACKGROUND Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis,increase insulin secretion,and improve blood glucose tolerance.However,its mechanism of action in the treatment of diabetic cardiomyopathy(DCM)remains unclear,hindering research efforts aimed at developing drugs specifically for the treatment of DCM.AIM To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment.METHODS We explored various databases and software,including the Traditional Chinese Medicine Systems Pharmacology Database,Uniport,PubChem,GenCards,String,and Cytoscape,to identify the active components and targets of Jiawei Jiaotai Pill,and the disease targets in DCM.Protein-protein interaction network,gene ontology,and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM.Molecular docking of key active components and core targets was verified using AutoDock software.RESULTS Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified.There were 100 common targets between the DCM and Jiawei Jiaotai Pills.Through this screening process,TNF,IL6,TP53,EGFR,INS,and other important targets were identified.These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase(MAPK)MAPK cascade,response to xenobiotic stimuli,response to hypoxia,positive regulation of gene expression,positive regulation of cell proliferation,negative regulation of the apoptotic process,and other biological processes.It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications,DCM,PI3K-Akt,interleukin-17,and MAPK signaling pathways.Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target.CONCLUSION The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress,cardiomyocyte apoptosis and fibrosis,and maintaining metabolic homeostasis.

Network pharmacology analysis combined with experimental verification of the molecular mechanism of Xihuang pill in treating liver cancer

Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of Xihuang pill in the treatment of liver cancer.In this work,we aim to explore the molecular mechanism of Xihuang pill in treating liver cancer.Methods:The functional components in Xihuang pill were collected from Traditional Chinese Medicine Database and Analysis Platform.The target genes of these components were also collected using Traditional Chinese Medicine Database and Analysis Platform.The target genes of liver cancer were predicted using GeneCards database.The intersecting genes were then analyzed with Venn diagrams.Kyoto Encyclopedia of Genes and Genomes and Database for Annotation,Visualization,and Integrated Discovery were used to analyze the pathway.Then,cell counting kit-8 was used to measure the half-maximal inhibitory concentration of Xihuang pills.The living dead cell staining method was used to observe the survival of cells.HepG2 cell apoptosis was tested by flow cytometry with fluorescein isothiocyanate/propidium iodide double staining method,and then the mitochondrial damage was also detected by flow cytometry.The expression of target genes was detected by quantitative real-time polymerase chain reaction.Results:A total of 130 compounds and 198 genes were identified as potential active ingredients and putative liver cancer‑related targets.We obtained 1,899 disease targets and 297 transcriptome targets from the database.Six drug-disease intersecting genes,CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3 were obtained.They are enrichment in apoptosis,PI3K-AKT signaling pathway,MAPK signaling pathway,pathways in cancer and p53 signaling pathway.Besides,it was found that the apoptosis rate of the HepG2 cells in Xihuang pill treated group was significantly higher than that of the control group.And the apoptosis rate gradually increased in a dose dependent manner of Xihuang pill treatment.Xihuang pill also induced the mitochondrial membrane potential damage.Compared with the control group,the expression level of CCNB1 and BIRC5 was induced,while the expression level of IGF2 was reduced after Xihuang pill treatment.Conclusion:Xihuang pill may act on six proteins(CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3)and cover multiple pathways to form a therapeutic network to treat liver cancer.

Study on the mechanism of Wuzi Yanzong pill in treating osteoporosis based on network pharmacology and molecular docking

Background:Based on network pharmacology and molecular docking,our study discussed the mechanism of Wuzi Yanzong pill in treating Osteoporosis(OP),which lays the foundation for drug development of OP.Methods:The chemical compounds and potential targets of Wuzi Yanzong pill were explored through TCMSP,PubChem,Swiss ADME and other databases.GeneCards,OMIM and Drugbank databases were used to obtain OP related targets.The intersection between the targets of Wuzi Yanzong pill and the related targets of OP was found by drawing a Venn diagram.PPI network was constructed with the STRING database and core targets were screened.The TCM-compound-action target-disease network was drawn using the Cytoscape software.The Metascape platform was used to find the pathways and functions for core target enrichment.Molecular docking validation of action compounds and core targets is completed by software such as Auto Dock Vina.Results:59 compounds and 707 action targets of Wuzi Yanzong pill were found.603 disease targets were selected,106 intersection targets were found using a Venn diagram,and 37 core targets were screened.By enrichment analysis,143 KEGG pathways,1026 GO biological processes,23 GO cell compositions and 60 GO molecular functions were obtained.The results of molecular docking showed that the effective compounds of Wuzi Yanzong pill,such as stigmasterol,quercetin,kaempferol andβ-sitosterol,had high binding activity with STAT3,TNF and IL6 core target proteins.Conclusion:Wuzi Yanzong Pill may play a role in treating OP by regulating STAT3,TNF,IL-6,TP53,VEGFA,JUN,AKT1,IL-1B,SRC,MMP9 and other pathways,as well as cancer-correlation,rheumatoid arthritis-correlation,MAPK,Th17 cell differentiation,IL-17,TNF signaling pathway and so on,to interpret Wuzi Yanzong pill’s clinic.

Exploring the mechanism of Huangjing pill in the treatment of Alzheimer’s disease based on network pharmacology and molecular docking

Objective To reveal the mechanism of Huangjing pill in treating Alzheimer’s disease(AD)based on network pharmacology and molecular docking technology.Methods We obtained the active ingredients and targets of Huangjing pill through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and supplemented the effective components by consulting literature and predicted targets through the PharmMapper database.We used DrugBank,the GeneCards,the TTD,and the OMIM database to collect targets of AD.The Venn diagram was drawn and the key targets of Huangjing pill in the treatment of AD were obtained by Venny 2.1 platform.The Cytoscape 3.8.1 software was used to construct a network diagram of“drugs-active ingredients-key targets-disease”.The protein-protein interaction(PPI)network diagram was constructed through the STRING 11.5 database.DAVID database was used for Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.AutoDock Vina1.1.2 software was used for molecular docking of the active components and core targets,and PyMOL 1.7.2.1 software was used for visual processing.Results After screening,we obtained 13 active ingredients and 116 targets of Huangjing Pill,1438 related targets for AD,and 75 common targets.566 items by GO enrichment analysis and 149 items related to KEGG pathway enrichment were obtained.Molecular docking results showed that there is a strong affinity between the key active ingredients and the core targets.Conclusion This study revealed that Huangjing pill could treat AD through multiple components,multiple targets and multiple pathways.

Mechanism of Zuojin Pill in the treatment of anxiety disorder and Major depressive disorder based on network pharmacology and molecular docking validation

Background:Zuojin Pill(ZJP)is a classic Chinese herbal prescription with good efficacy in the treatment of Anxiety disorder(AD)and Major depressive disorder(MDD).Nevertheless,the potential mechanisms of ZJP remain unclear.Based on network pharmacology and molecular docking methods,this study aims to elucidate the possible mechanism of ZJP in the treatment of AD and MDD.Methods:The components and targets of Rhizoma Coptidis and Fructus Evodiae were collected from TCMSP,ETCM,HERB,SWISSADME and STITCH databases.The disease targets related to MDD and AD were collected from DISGENET,GENECARDS and OMIM databases.Protein-protein interaction network was constructed by STRING database,GO and KEGG enrichment analysis was performed by METASCAPE database,and“drugs-components-targets network”was constructed by Cytoscape software.Molecular docking verification was performed by Sailvina2.0 software.Results:ZJP may act on AKT1,IL6,TNF and other targets through caffeine,isorhamnetin,berberine and other components,regulating the Inflammatory mediator regulation of TRP channels,Serotonergic synapse,Dopaminergic synapse,PI3K/AKT signaling pathway,and other pathways.The results of molecular docking showed that berberine had the best binding activity with the core target.Conclusion:ZJP can exert anti-anxiety and anti-depression effects through multiple components,multiple targets and multiple pathways.

Integrated UHPLC-MS and network pharmacology to explore the active constituents and pharmacological mechanisms of Shenzao dripping pills against coronary heart disease

Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms of SZDP are unknown.Methods:In this study,ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry was used to identify the chemical components in extracts and medicated plasma of SZDP.Subsequently,we performed network pharmacology methods,including target prediction by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,protein-protein interaction network via STRING database;further,the key targets and compounds were screened using Cytoscape.Finally,the key targets and compounds were validated by molecular docking.Results:72 chemical constituents were identified from SZDP by high performance liquid chromatography and mass spectrometry technology.Among the components absorbed into plasma by SZDP,24 prototype components and 9 metabolized components were identified.The network pharmacology analysis of the prototype components showed that there are 13 key compounds(including ginsenoside Rc,Rb1,Rb2,ferulic acid,etc.),90 proteins(including proto-oncogene tyrosine-protein kinase Src,nuclear receptor subfamily 3 group C member 1,caspase-3,etc.),and 10 pathways(including estrogen,IL-17 and VEGF signaling pathway,etc.)that play an essential role in the treatment of coronary heart disease with SZDP.In addition,the results of molecular docking revealed that ginsenosides Rc,Rb2 and Rb1 have strong binding activities to the caspase-3,as well as ginsenoside Rb2 to the nuclear receptor subfamily 3 group C member 1.Conclusion:This study showed that SZDP might act through multiple chemical constituents and targets against coronary heart disease.

Mechanism of Cangfu Daotan pill in treating polycystic ovary syndrome based on network pharmacology

Objective:To explore the target and molecular mechanism of Cangfu Daotan pill in the treatment of polycystic ovary syndrome(PCOS)by network pharmacology.Methods:The main active components and corresponding targets of Cangfu Daotan pills were searched in the database of traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).GeneCards database and OMIM database were used to search for disease targets of PCOS;the intersection of the target of Cangfu Daotan pill and the disease target of PCOS was drawn by using R to obtain the intersection gene;protein interaction network was constructed through String online database;Cytoscape(3.2.1)was used to construct a‘major component-disease-target’network diagram and analyze the important nodes therein;KEGG and GO enrichment analyses were carried out on the obtained intersection genes through org data packets in R.Results:Network pharmacology analysis showed that 151 active ingredients involved in pathways were screened out,140 of which acted on PCOS,and 105 potential targets were used to exert therapeutic effects.After enrichment,1900 GO biological signals and 143 KEGG signals were obtained,and the first 14 drug targets were screened out.Conclusion:Cangfu Daotan pill may mediate gene transcription regulation,lipid metabolism,inflammatory micro environment,insulin resistance,sex hormone axis,arteriosclerosis,interleukin immune regulation and other signals through regulating key targets of JUN,MAPK3,HSP90AA1,MAPK1,ESR1,NR3C1,APP,MAPK14,MAPK8,VEGFA,EGFR,RB1,AR,IL6,mediate gene transcription regulation,lipid metabolism,inflammatory micro environment,insulin resistance,sex hormone axis,arteriosclerosis,interleukin immune regulation,etc.,and regulate biological processes such as drug reaction,nutrition and lipid metabolism,active oxygen,sugar metabolism,steroid hormone,etc.to achieve the effect of treating polycystic ovary syndrome.

Potential targets and mechanism of Xingxiao Pill for the treatment of lung cancer were analyzed based on network pharmacology and molecular docking

Objective:To analyze the potential targets and mechanism of Xingxiao Pill for the treatment of lung cancer based on network pharmacology and molecular docking,providing reference for the research and clinical development of Xingxiao Pill.Method:The main chemical constituents and their targets of Xingxiao Pill was obtained through BATMAN-TCM database.Effective compounds were screened based on SwissADME and their targets were predicted by SwissTargetPrediction.Main lung cancer targets were obtained and integrated through GeneCards,OMIM(OMIM-Gene-Map-Retrieval),TTD and DRUGBANK databases.The intersection targets of Xingxiao Pill for lung cancer were obtained by Venn.The String platform was used to obtain the intersection targets.The core targets of Xingxiao Pill for lung cancer were screened by BisoGenet3.0.The Metasacpe database was used to analyze the biological processes and pathways involved in intersection targets.Cytoscape3.7.2 software was used to construct the"active ingredients of Xingxiao Pill-targets-pathways"network.Finally,Autodock was used for molecular docking verification.Results:The core active components of Xingxiao Pill for the treatment of lung cancer were morin,testosterone,17-Beta-Estradiol,alphaEstradiol,muscone,commiferin,commisterone,octyl acetate,etc.The primary pathways mainly included PI3K/Akt,MTOR,MAPK signaling pathway and MicroRNAs in cancer,etc.It has been proved that the combination of testosterone and estradiol with AKT1,SIRT7 and MDM2 was stable and could be used as reference.Conclusion:This study preliminarily revealed the mechanism of Xingxiao Pill on treating lung cancer with multiple components,targets and pathways,providing some ideas and references for clinical application and basic research in the future.

Study on the mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking

Objective:To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to retrieve and screen the active components of each Chinese medicine in Guizhi Fuling pill.The main active components of the medicine were screened through the network analysis function of Cytoscape software,and the target of the main active components of the medicine was found in UniProt database.Using genecards,OMIM,digsee,TTD,and drugbank database to retrieve the related targets of ovarian cancer.The interaction between the target of the main active components of the drug and the related target of ovarian cancer was obtained by R software.The intersection targets are imported into string database for PPI analysis,and then the results are imported into Cytoscape to get the hub gene using the cyclohubba plug-in.KEGG pathway analysis and go enrichment analysis were carried out in metascape database.At last,autodock tools was used to verify the main active ingredients and the selected target proteins.PyMOL and LigPlus software visualized the results.Results:The main active components of Guizhi Fuling pills were quercetin,β-sitosterol,kaempferol,hederagenin,catechin,ellagic acid,stigmasterol and Douglas fir.There are 20 pivotal genes of drug effect on ovarian cancer,including VEGFA,AKT1,mapk8,Jun,MMP9,IL6,TNF,CXCL8,PTGS2,TP53,CASP3,mapk1,EGF,ESR1,EGFR,Myc,FOS,CCL2,CXCL8 and IL1B.According to KEGG pathway analysis,10 pathways with the highest correlation were found:cancer signaling pathway,MAPK signaling pathway,fluid shear stress and atherosclerosis,hepatitis B,trypanosomiasis,age-rage signaling pathway in diabetic complications,tumor necrosis factor signaling pathway,pertussis,IL-17 signaling pathway,and bladder cancer.Go enrichment analysis has screened out 10 important items in molecular biological function,cell components and biological process.The proteins encoded by IL6,mapk1,VEGFA,AKT1,TP53,TNF and CCL2 were used as targets to dock with the main active components of the drug respectively,and the best results were TNFαand ellagic acid.Conclusion:The main active components of Guizhi Fuling pill regulate multiple signal pathways by regulating IL6,VEGFA,CCL2,TNF,MMP9 and other cytokines,and inhibit the proliferation and metastasis of cancer cells.

Research on the Mechanism of the treatment of non‑alcoholic fatty liver by Jianwei Gexia Zhuyu Decoction based on network pharmacology and molecular docking

Objective:To analyse the key compounds,targets and pathways of the treatment of non‑alcoholic fatty liver disease(NAFLD)by Jianwei Gexia Zhuyu Decoction based on network pharmacology,in order to explore the molecular mechanism of its therapeutic effects.Methods:The differential genes between sick and normal conditions were screened by GEO‑Datasets,and the heat map and volcano map were drawn.The active compounds in Jianwei Gexia Zhuyu Decoction were searched by TCMSP platform and Drugbank database.OB≥30%and DL≥0.18 were set as thresholds to screen potential active compounds and action targets.The molecular target maps of Jianwei Gexia Zhuyu Decoction and NAFLD differential genes were constructed,and the PPI network and network topology parameters were obtained by STRING database.The PPI network and network topology parameters were visually analyzed by Cytoscape,and the core regulatory genes were screened.At the same time,the SwissDock platform was used to dock the main active components with the target.The main pathways were determined by GO biological function enrichment analysis and KEGG metabolic pathway enrichment analysis by DAVID.Results:After screening,377 differential genes(127 up‑regulated genes and 250 down‑regulated genes),225 active compounds of Jianwei Gexia Zhuyu Decoction,308 corresponding targets were obtained;14 key targets were screened,corresponding to 168 compounds,and the key targets involved MYC,FOSL2,FOS,etc.The results of GO functional enrichment analysis showed that Jianwei Gexia Zhuyu Decoction mainly regulated the activity expression of DNA binding transcriptional activator and the specific transcription of RNA polymeraseⅡ;The results of molecular docking showed that the main active components quercetin and baicalein had good binding activity with VCAM1,HSPB1,MYC,JUN and so on;The results of KEGG enrichment analysis showed that it was mainly involved in IL‑17 signal pathway,Wnt receptor signal pathway,NF‑κB signal pathway,TNF signal pathway and AGE‑RAGE signal pathway in diabetic complications.Conclusion:Through the interaction of multi‑components and multi‑targets,Jianwei Gexia Zhuyu Decoction has achieved the goal of overall treatment of NAFLD from many ways.The application of network pharmacology provides a new research approach and scientific basis for further study on the mechanism of Jianwei Gexia Zhuyu Decoction in the treatment of NAFLD.

Network pharmacology-based approach to investigate the mechanisms of Guizhi Fuling pill in the treatment of atherosclerosis

Objective:To investigate the mechanism of action of Guizhi Fuling pill in the treatment of atherosclerosis with network pharmacology.Methods:The active components of Guizhi Fuling pill were screened by specific ADME features on Traditional Chinese Medicine Systems Pharmacology platform,and their targets were obtained.Targets of atherosclerosis were extracted and screened from GeneCards database,OMIM database,DrugBank database and DisGeNET database,and the intersection of component targets and disease targets were regarded as potential targets.The protein-protein interaction network of potential targets was constructed by STRING database and Cytoscape 3.7.2.GO analysis and KEGG pathway analysis of potential targets were performed by Metascape platform.The“drugs-componenst-targets-pathways”network was constructed by Cytoscape 3.7.2.SwissDock was used for molecular docking of active components and key targets.Results:The main components of Guizhi Fuling pill in the treatment of atherosclerosis were quercetin,beta-sitosterol,kaempfero,hederagenin,baicalein,etc.The key targets mainly included PGST2,RELA,AKT1,etc.Molecular docking analysis showed that the binding energy of the main active components to the core target was less than-7 kcal/mol.The associated pathways mainly included fluid shear stress and atherosclerosis,PI3K-Akt signaling pathway and AGE-RAGE signaling pathway.Conclusion:Through this study,we initially revealed the possible mechanism of Guizhi Fuling pill in treating atherosclerosis through anti-inflammatory,reducing blood lipids,and regulating endothelial function.

Theory and mechanism analysis of Wuji Pill in Anti-lung Cancer:A study based on network pharmacology and molecular docking technology

Background:To explore the effective components and mechanism of Classic ancient prescription Wuji pill on lung cancer(LC)with the help of network pharmacology and molecular docking technology.Methods:TCMSP database,Chinese Pharmacopoeia(2020 Edition)and related literature were searched to identify the main chemical composition and targets of constituent drugs in Wuji pill,including Houpo(Magnoliae Officinalis Cortex),Huangqin(Scutellariae Radix),Badou(Crotonis Fructus),Huanglian(Coptidis Rhizoma)and Renshen(Ginseng Radix et Rhizoma).Meanwhile,Genecards,OMIM,TTD,Drugbank and PharmGkb databases were used to obtain the main targets of LC.The"chemical compound-target"network was constructed by using Cytoscape 3.8.2 software with the disease drug intersection gene as the research target.The PPI network was constructed by using the string database for protein interaction analysis,and the core target genes were sorted out.The Gene ontology go function enrichment analysis and KEGG signal pathway enrichment analysis were carried out based on the ClusterProfiler of R software.Finally,the Autodock Vina software was used to conduct molecular docking between the core target with high value and the key components.Results:A total of 60 active components,190 corresponding targets and 2516 GO and 163 KEGG pathways of Wuji pill were screened out,including 179 potential targets of LC.The core targets were ESR1,CDKN1A,TP53,NR3C1,MAPK1,AKT1,MAPK8,JUN,RELA,the core components were quercetin,kaempferol,β-sitosterol,stigmasterol,tetrahedron,protoopioid,etc,and the core pathways were PI3K-Akt,MAPK,IL-17,etc.Conclusion:This study preliminarily revealed the mechanism of action of Wuji pill on multi component-multi target-multi pathway of LC,which provided reference for the further clinical development and research of Wuji pill.

Study on the feasibility of Danggui Longhui pill in the treatment of COVID-19 based on network pharmacology

Background:To preliminary the feasibility and the potential mechanism of classic ancient prescription of Chinese medicine Danggui Longhui pill in the treatment of COVID-19 based on network pharmacology.Methods:The active constituents and acting targets of classic ancient prescription of Chinese medicine Danggui Longhui pill were collected and screen out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platformand Genecard databases.Cytoscape-v3.7.2 software and Search Tool for the Retrieval of Interacting Genes databases were used to construct and analyze networks and protein-protein interaction network.The R programming language software combined with Bioconductor were used to analyze gene function(the gene oncology)and gene pathway(Kyoto Encyclopedia of Genes and Genomes)enrichment of the targets.Results:Seventy-three active constituents of classic ancient prescription of Chinese medicine classic ancient prescription of Chinese medicine Danggui Longhui pill played its effect on 48 targets through 83 signal pathway were effected,including advanced glycation end products/receptor for advanced glycation end products,interleukin-17,tumorecrosis factor,NOD-like receptor and cytokine-cytokine receptor interaction.Conclusion:Classic ancient prescription of Chinese medicine Danggui Longhui pill has certain feasibility in the treatment of COVID-19.To predict the potential mechanism of classic ancient prescription of Chinese medicine Danggui Longhui pill in the treatment of COVID-19 may be related to the regulate inflammation and immune system.

Mechanism of Wumei Pill in the Treatment of Non-Erosive reflux disease from the Perspective of Network Pharmacology and Molecular docking

Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.

Mechanism of action of Zhuyu Annao pill in mice with cerebral intrahemorrhage based on TLR4

Objective:To explore the protective effect and possible mechanism of action of Zhuyu Annao pill in mice with intracerebral hemorrhage(ICH).Methods:Sixty mice were divided into the control group,hemorrhage group,drug-treated group(after hemorrhage),TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group(after hemorrhage) with 12 in each group.Model of autologous ICH was established in all groups.After drilling and 12 h of fasting,models in the control group hemorrhage group and TLR4-knockout hemorrhage group were all drenched with 10 mL/kg distilled water by intragastric administration.Models in the drug-treated group and TLR4-knockout hemorrhage + drugtreated group were drenched with 6.25 g/kg of Zhuyu Annao pill.All groups were treated for 7 d.Longa scoring method was used to measure the neurological defect scores and determine the brain water contents of all groups;ELISA was employed to detect the inflammatory factor interleukin(IL)-6,tumor necrosis factor- α(TNF- α) and IL-1β in brain tissues;and Western blot was applied to test the expression quantities of apoptotic protein Bax and anti-apoptotic protein Bcl-2 in brain tissues.Results:At day 3 and7,compared with the hemorrhage group,the neurological defect scores of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group decreased significantly(P<0.05) Compared with the hemorrhage group,the brain water contents of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group reduced significantly(P<0.05) Compared with the hemorrhage group,the inflammatory factor IL-6,TNF-α and IL-1β of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group decreased significantly(P<0.05).Compared with the hemorrhage group,the expression of apoptotic protein Bax of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage+ drug-treated group decreased significantly and the expression of anti-apoptotic protein Bcl-2 increased significantly(P<0.05).Conclusions:Zhuyu Annao pill can alleviateencephaledema for mice with ICH and reduce inflammatory responsesandnerve cell apoptosis.TLR4 can mediate inflammatory injury induced by ICH.Thus,Zhuyu Annao pill can play a protective role for brains by decreasing the expression of TLR4.

The mechanism of Wumei Wan on treating diabetes enteropathy based on the network pharmacology

Objective:To explore the potential mechanism of Wumei Wan(WMW)in treating diabetes enteropathy(DE)basing on network pharmacology.Methods:The effective compound of WMW were collected by TCMSP,the potential target of WMW was obtained by means of PubChem and Swiss target prediction online tools,and the disease target of DE was obtained by Genecards,TTD and DisGeNET databases,Cytoscape 3.7.2 software was used to construct active ingredients of WMW-potential target-DE network,protein interaction network(PPI)was constructed by STRING database.In order to understanding the mechanism of WMW treating in DE,Omicshare platform was used for GO analysis and KEGG pathway enrichment analysis.The analysis results were verified through docking by Discovery Studio 2016.Results:Total of 128 active components and 139 targets of WMW were screened out from the ten drugs.A total of 714 disease targets were screened out from the disease databases.24 common targets were identified from both WMW and DE.AKT1,MMP9,SRC,PTGS2,PPARG,NOS2,etc.are potential major targets of WMW in the treatment of DE.61 entries(p<0.05)were enriched in GO biological process function related to fatty acid anabolism and ligand receptor binding,as unsaturated fatty acid metabolic process,icosanoid metabolic process,enzyme linked receptor protein signaling pathway,protein amino acid phosphorylation,cellular response to insulin stimulus.A total of 72 signaling pathways were obtained through KEGG pathway analysis(p<0.05).The signaling pathways closely related to DE are including relaxin signaling pathway,EGFR tyrosine kinase inhibitor resistance,CLRs signaling pathway,and VEGF signaling pathway.Conclusion:This study preliminarily revealed the material basis and mechanism of WMW in the treatment of DE from the synergistic aspects of intestinal immune balance,gastrointestinal wall structure reconstruction,intestinal microvascular disorder and neuronal activity.