Evaluation of the famous classic formula Sanhua decoction based on network pharmacology and multi-component quantitative analysis

Background:Sanhua decoction has significant effects in the treatment of stroke.The study of the Sanhua decoction material benchmark was carried out to analyze the value transfer relationship between the Chinese herbal pieces and the substance benchmark.Methods:Network pharmacology was employed to investigate the potential active components and molecular mechanisms of Sanhua decoction in the treatment of stroke.15 batches of Sanhua decoction lyophilized powder were prepared using traditional formulas and subjected to high-performance liquid chromatography analysis to generate fingerprints of the Sanhua decoction substance benchmarks.Then,a multi-component quantitative analysis method was established,allowing for the simultaneous determination of ten components,to study the transfer of quantity values between pieces and substance benchmarks.Results:60 active ingredients were screened from Sanhua decoction by network pharmacology,of which gallic acid,magnolol honokiol,physcion,and aloe-emodin may have a greater effect than other active components.63 key targets and 134 pathways were predicted as the potential mechanism of Sanhua decoction in treating stroke.The fingerprint similarity of the Sanhua decoction substance benchmarks was found to be good among the 15 batches,confirming the 19 common peaks.The content of the 10 components was basically consistent.The components’transfer rates were within 30%of their respective means.Conclusions:This study provided a comprehensive and reliable strategy for the quality evaluation of Sanhua decoction substance benchmarks and held significant importance in improving its application value.

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.

Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics

Nonalcoholic fatty liver disease(NAFLD)has developed into the most common chronic liver disease and can lead to liver cancer.Our laboratory previously developed a novel prescription for NAFLD,“Eight Zhes Decoction”(EZD),which has shown good curative effects in clinical practice.However,the pharmacodynamic material basis and mechanism have not yet been revealed.A strategy integrating lipidomics,network pharmacology and pharmacokinetics was used to reveal the active components and mechanisms of EZD against NAFLD.The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice.Furthermore,glycerophospholipid metabolism,arachidonic acid metabolism,glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA(PLA2G4A)and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid,12(S)-hydroxyeicosatetraenoic acid,leukotriene B4,prostaglandin E2,phosphatidylcholines(PCs)and triacylglycerols(TGs)as the main lipids were found to be involved in the treatment of NAFLD by EZD.Importantly,naringenin,artemetin,canadine,and bicuculline were identified as the active ingredients of EZD against NAFLD;in particular,naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver.This research provides valuable data and theoretical support for the application of EZD against NAFLD.

Initial steps on the analysis of the underlying pharmacological mechanisms of Wendan decoction on sudden deafness using network pharmacology and molecular docking

Background:Despite its widespread therapeutic use and effectiveness,the underlying pharmacologic mechanisms of Wendan decoction(WDD)and how it works to treat sudden deafness(SD)remain unclear.In this study,the pharmacological mechanisms of WDD underlying SD were analyzed using network pharmacology and molecular docking.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was employed to identify the active compounds and target genes of WDD,and genes associated with SD were screened on five databases.RGUI conducted Gene Ontology(GO)functional and the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A compound-target network was established using Cytoscape,and the STRING database created a protein-protein interaction(PPI)network to identify the key compounds and targets.Subsequently,a network of crucial compound-target was generated for further molecular docking analysis.For molecular docking simulations of the macromolecular target proteins and their matching ligand molecules,AutoDock Vina and AutoDockTool were utilized.Results:TCMSP identified 162 active target genes and 36 active compounds for WDD.The active target genes were compared with the 2271 genes associated with SD to identify 70 intersecting active target genes linked to 34 active compounds.The GO functional enrichment and KEGG pathway enrichment analyses were undertaken,and compound–target,and PPI networks were built.The key compounds and protein targets were identified and integrated to form a key compound–target network.Eventually,molecular docking was performed to investigate the interactions of the protein targets with their respective compounds.Conclusion:This study highlights the mechanisms of multi-compounds,targets,and pathways of WDD acting on SD and provides further evidence of crucial compounds and their matching target proteins of WDD acting on SD.

Integrating serum pharmacochemistry,network pharmacology and metabolomics analysis to explore the possible mechanism of Qingjiehuagong decoction in the treatment of acute pancreatitis

Background:The Qingjiehuagong decoction(QJHGD),which has been used in clinical trials to treat acute pancreatitis(AP),has demonstrated encouraging results.Methods:In this particular investigation,we used both metabolomics and network pharmacology to investigate the fundamental processes and targets that QJHGFD employs to cure AP.Results:Using a cerulein-induced rat model of AP,we showed that QJHGD effectively improved pancreatic tissue damage and reduced serum levels of AMY,LPS,IL-1β,IL-6,IL-8 and TNF-α.In total,28 blood entry compounds derived from QJHGD were identified by ultra-performance liquid chromatography-high resolution mass spectrometry technology.The intersecting target genes of 108 genes associated with identified compounds in QJHGD and AP disease genes were identified using a network pharmacology approach.The protein interaction network revealed AKT1,TNF-α,IL-6,VEGFA,and TP53 as important targets.Gene ontology analysis showed that response to stimulus,molecular function regulator and organelle part were the main functions,and Kyoto Encyclopedia of Genes and Genomes analysis showed that 20 pathways such as AGE-RAGE signaling pathway in diabetic complications and the IL-17 signaling pathway were the main pathways involved in the anti-AP effects of QJHGD.Thirty-two potential metabolic markers and 13 possible metabolic pathways were identified by metabolomics analysis.Combined network pharmacological analysis revealed that QJHGD affects four metabolic pathways(tryptophan metabolism;glycolysis and gluconeogenesis metabolism;valine,leucine and isoleucine degradation metabolism;the urea cycle and metabolism of arginine,proline,glutamate,aspartate and asparagine),five metabolites(indole-3-acetate,pyruvate,methylmalonate,L-citrulline,N-acetyl-l-glutamate)and four related targets(AKT1,ALDH2,NOS2,NOS3)to combat inflammation.The strong affinity of QJHGD’s interactions with its primary targets was established by molecular docking and molecular dynamics simulations.Conclusion:This research investigate the critical targets and mechanisms of QJHGFD for treating AP.The results of this investigation provide novel tactics and complementary techniques for the clinical treatment of AP.

Exploring the pharmacological mechanism of Wuzhuyu decoction on hepatocellular carcinoma using network pharmacology

BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.

Exploring the mechanism of Yishen Daluo decoction in the treatment of multiple sclerosis based on network pharmacology and in vitro experiments

Objective:To explore the mechanism and related active components of Yishen Daluo decoction(YSDLD)in treating multiple sclerosis(MS).Methods:Targets of YSDLD were collected through the TCMSP,Chemistry,and TCMID databases.The MS targets were collected through OMIM,DrugBank,Gencards,TTD,and Pharmgkb databases.We built“componentetarget”network diagrams and proteineprotein interaction(PPI)diagrams and performed topological analysis.The targets were subjected to GO and KEGG enrichment analysis.Molecular docking verification was conducted on selected targets and molecules.Finally,in vitro experiments were con-ducted.BV2 cells were induced by lipopolysaccharide for model establishment.CCK8 experiment was conducted to explore the effect of YSDLD and RT-qPCR technology was used to explore the expression of key targets.Results:There were 184 active components in YSDLD and 898 targets of its action.There were 940 MS targets,and 215 targets were shared by YSDLD and MS.According to the“componentetarget”diagram,the top five key components included quercetin,kaempferol,beta-sitosterol,stigmasterol,and nar-ingenin.IL-6,IL-1 b,TNF-α,AKT1,and VEGFA were the important targets identified by PPI network to-pology analysis.A total of 564 functions were identified by GO enrichment analysis(P<0.01),mainly involving inflammatory response,hypoxia response,plasma membrane,neuronal cell body,protein phosphatase binding,and cytokine activity.KEGG enrichment analysis enriched 98 pathways(P<.01).YSDLD at the concentration of 20 m g/mL had no effect on BV2 cells.RT-qPCR indicated that YSDLD at the concentrations of 15 m g/mL and 20 m g/mL alleviated LPS-induced inflammatory injury and lowered the content of inflammatory factors(P<0.05).Conclusion:In this paper,the network pharmacology and in vitro experiments were used to explore the potential mechanism of YSDLD in treating MS.The research provides a good basis for the development of YSDLD and drugs for MS in future.

Fang-Xia-Dihuang decoction inhibits breast cancer progression induced by psychological stress via down-regulation of PI3K/AKT and JAK2/STAT3 pathways:An in vivo and a network pharmacology assessment

Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.

Network pharmacology and molecular docking-based analyses to predict the potential mechanism of Huangqin decoction in treating colorectal cancer

BACKGROUND To analyze the potential action mechanism of Huangqin decoction(HQD)in colorectal cancer(CRC)treatment on the basis of network pharmacology and molecular docking.AIM To investigate the molecular mechanisms of HQD for CRC treatment by using network pharmacology and molecular docking.METHODS All HQD active ingredients were searched using the Systematic Pharmacology and Traditional Chinese Medicine Systems Pharmacology databases and the Bioinformatics Analysis Tool for Molecular Mechanisms in traditional Chinese medicine.Then,the targets of the active ingredients were screened.The abbreviations of protein targets were obtained from the UniProt database.A“drug–compound–target”network was constructed to screen for some main active ingredients.Some targets related to the therapeutic effect of CRC were obtained from the GeneCards,DisGeNET,Therapeutic Target Database,and Online Mendelian Inheritance in Man databases.The intersection of targets of Chinese herbs and CRC was taken.A Venn diagram was drawn to construct the intersection target interactions network by referring to the STRING database.Topological analysis of the protein interaction network was performed using Cytoscape 3.7.2 software to screen the core HQD targets for CRC.The core targets were imported into the DAVID 6.8 analysis website for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and visualization.Finally,molecular docking was performed using AutoDockTool and PyMOL for validation.RESULTS In total,280 potential drug-active ingredients were present in HQD,including 1474 targets of the drug-active ingredients.The main active ingredients identified were betulin,tetrahydropalmatine,and quercetin.In total,10249 CRC-related targets and 1014 drug-disease intersecting targets were identified,including 28 core targets of action such as Jun proto-oncogene,AP-1 transcription factor subunit,signal transducer and activator of transcription 3,tumor protein p53,vascular endothelial growth factor,and AKT serine/threonine kinase 1.The gene ontology enrichment functional analysis yielded 503 enrichment results,including 406 biological processes that were mainly related to the positive regulation of both gene expression and transcription and cellular response to hypoxia,etc.In total,38 cellular components were primarily related to polymer complexes,transcription factor complexes,and platelet alpha granule lumen.Then,59 molecular functions were closely related to the binding of enzymes,homologous proteins,and transcription factors.The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 139 enrichment results,involving epidermal growth factor receptor tyrosine kinase inhibitor resistance and HIF-1 and mitogen-activated protein kinase signaling pathways.CONCLUSION HQD can play a role in CRC treatment through the“multi-component-target–pathway”.The active ingredients betulin,tetrahydropalmatine,and quercetin may act on targets such as Jun proto-oncogene,AP-1 transcription factor subunit,signal transducer and activator of transcription 3,tumor protein p53,vascular endothelial growth factor,and AKT serine/threonine kinase 1,which in turn regulate HIF-1 and mitogen-activated protein kinase signaling pathways in CRC treatment.The molecular docking junction clarified that all four key target proteins could bind strongly to the main HQD active ingredients.This indicates that HQD could slow down CRC progression by modulating multiple targets and signaling pathways.

Mechanism of Wulan Shisanwei Decoction in Treating Hypertension Complicated with Hyperlipidemia Based on Network Pharmacology

[Objectives]To screen out the main effective components of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia based on the method of network pharmacology,predict the target and explore the possible mechanism.[Methods]13 components of Wulan Shisanwei Decoction were searched on the TCMSP data platform,the corresponding active components were found and the corresponding targets were searched in Pubchem database.GeneCards database was used to screen the corresponding targets of hypertension and hyperlipidemia.The core target PPI network of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia was constructed by processing in STRING database.The effective data were imported into Cytoscape 3.8.0 to analyze the network topology parameters,and they were screened according to the degree value greater than the average value.Finally,the relevant information about the core target of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia was obtained.GO enrichment analysis and KEGG pathway analysis were carried out for core targets in DAVID database.The visualization map of"drug-component-target-disease"was drawn by Cytoscape 3.8.0.[Results]A total of 85 active components were obtained from Wulan Shisanwei Decoction,and there were 1532 corresponding targets.A total of 303 key targets were obtained by intersecting corresponding drug targets with disease targets.3178 biological processes were obtained by GO analysis(P<0.05)and 192 signaling pathways were obtained by KEGG enrichment analysis(P<0.05).[Conclusions]It was predicted that the main active components of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia were stigmasterol,acacetin,pectolinarigenin,isorhamnetin,alizarin,quercetin,nordamnacanthal,kaempferol,luteolin,glyceollin,kushenol,t,3-methylkempferol,ellagic acid,etc.20 core targets were selected in the treatment of hypertension complicated with hyperlipidemia:SRC,STAT3,HSP90AA1,MAPK1,MAPK3,PIK3R1,HRAS,GRB2,PIK3CA,AKT1,PTPN11,ESR1,LCK,EGFR,FYN,EP300,RELA,JUN,LYN,RHOA.These targets were involved in PI3K-Akt signaling pathway,lipid and atherosclerosis,proteoglycan in cancer,Ras signaling pathway,etc.to exert a response to oxidative stress,cellular response to chemical stress,peptidyl-tyrosine phosphorylation and peptide tyrosine modification,and can intervene in the early stage of the disease.It may be the potential mechanism of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia.

Study on the Molecular Mechanism of Danggui Buxue Decoction in Intervention of Perimenopausal Syndrome Based on Network Pharmacology and Molecular Docking

[Objectives]This study was conducted to explore the intervention mechanism of Danggui Buxue Decoction in perimenopausal syndrome based on network pharmacology and molecular docking.[Methods]The chemical components and targets of Danggui Buxue Decoction were acquired through the TCMSP database,and the main targets of perimenopausal syndrome were obtained through the GeneCards database.The component targets and disease targets were intersected,and combining with active components and Chinese herbs in the decoction,a traditional Chinese medicine-component-target network was constructed using Cytoscape 3.7.1 software.The STRING platform was employed for protein-protein interaction analysis.The DAVID analysis platform was used to conduct target GO and KEGG enrichment analysis,so as to predict the action mechanism Danggui Buxue Decoction.Finally,an active component-disease target-signal pathway network diagram was constructed.[Results]Twenty two components in Danggui Buxue Decoction related to perimenopausal syndrome and 120 corresponding targets were obtained,including active components such as 1,7-dihydroxy-3,9-dimquercetin and kaempferol,and key targets such as TNF,ESR1 and PPARG.The results of GO analysis and KEEG analysis indicated that Danggui Buxue Decoction might regulate the transcription of RNA polymerase II promoter,DNA templating,gene expression,signal transduction,hypoxia response and other biological processes by regulating multiple signal pathways such as chemical carcinogenesis-receptor activation,cancer pathways,lipid and atherosclerosis,tryptophan metabolism,malaria,steroid hormone biosynthesis and chemical carcinogenesis-DNA adduct.[Conclusions]Danggui Buxue Decoction intervenes in perimenopausal syndrome through multiple components,targets and pathways,providing a basis for elucidating the intervention mechanism of Danggui Buxue Decoction and expanding its clinical application.

Mechanism of action of Zhishi Daozhi decoction in the treatment of diarrhea based on network pharmacology and molecular docking

Background:To explore the mechanism of action of Zhishi Daozhi decoction in treating diarrhea using network pharmacology and molecular docking.Methods:The pharmacological components and targets of Zhishi Daozhi decoction were searched by The TCMSP and Uniprot database and the disease genes of diarrhea were obtained from GeneCard and diagenetic databases.The network software venny 2.1.0 was used to screen the intersection targets of Zhishi Daozhi decoction in treating diarrhea.STRING database was used to construct protein interaction network,Metascape database analysis platform for gene ontology enrichment and Kyoto Gene and Genome Encyclopedia pathway enrichment analysis.Using Cytoscape 3.9.1 software to map the“Chinese herbal medicine-active ingredient-target”network and perform network topology to identify the core genes.Selecting core genes and critical components for molecular docking.Results:203 active ingredients and 259 target genes were obtained from Zhishi Daozhi decoction,206 genes were cross-linked with the disease gene control after de-duplication,1001 entries meeting the screening criteria were obtained after gene ontology enrichment analysis,and 169 entries were obtained after Kyoto Gene and Genome Encyclopedia enrichment analysis,in which the biological processes were mainly enriched in the cellular responses to lipids,hormones,radiation,growth factors,and cell fractionation.The Kyoto Gene and Genome Encyclopedia pathway enrichment analysis suggested that it mainly covers the cancer pathway,hepatitis B,cellular senescence,IL-17 signaling pathway,PI3K-Akt signaling pathway,etc.The molecular docking results showed that the vital active ingredients,such as lignocaine and quercetin,with better binding activity to the vital core targets,such as MMP3,AKT1,and CCL2.Conclusion:The active ingredients such as quercetin and luteolin in Zhishi Daozhi decoction may act through signaling pathways such as IL-17 signaling pathway,PI3K-Akt signaling pathway,TGF-βsignaling pathway,and other pathways,and act on the critical core targets such as MMP3,AKT1,HSP90AA1,FOS,CCL2,and TGFB1 to enhance intestinal barrier function,reduce the inflammatory response and regulate intestinal flora,thus achieving the purpose of treating diarrhea.

Deciphering the potential mechanism of Siwu decoction for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Siwu decoction(SWD)is a traditional Chinese herbal decoction commonly used for treating various symptoms of blood deficiency and blood stasis,including cancer-related anemia(CRA).However,due to its complex composition,the key active ingredients and underlying mechanisms of its therapeutic effects often remain unknown.This research aims to use network pharmacology and molecular docking technology to systematically elucidate the potential mechanisms underlying the efficacy of SWD in treating cancer-related anemia.Methods:The key constituents of SWD were procured from the TCMSP database.Leveraging the Swiss ADME and Swiss Target Prediction databases,potential targets were recognized.Disease-related targets were assembled via the GeneCards and DrugBank databases.Constructing the PPI network involved the utilization of the STRING database,followed by visualization through Cytoscape 3.9.1 software.Subsequently,GO and KEGG enrichment analysis was conducted utilizing the DAVID database,with visual analysis performed on the macrobiotic platform.For molecular docking,the Autodock software was employed,and the molecular docking outcomes were visualized using the PyMOL software.Results:In this investigation,a comprehensive revelation of 18 primary active compounds and 511 associated targets linked to CRA was accomplished.The outcomes of protein-protein interaction(PPI)analysis unequivocally identified AKT1,EGFR,SRC,VEGFA,HRAS,MAPK3,and STAT3 as pivotal proteins within the SWD’s framework for effective CRA intervention.Notably,signaling pathways such as the HIF-1,JAK-STAT,TNF-α,and PI3K-Akt pathways,intricately involved in hematopoietic stem cell proliferation,differentiation,and inflammatory response,emerged as closely intertwined with the therapeutic application of SWD for CRA treatment.The congruence between these potential targets and SWD’s primary therapeutic constituents for CRA treatment was substantiated by the outcomes of molecular docking analysis.Conclusion:This work provided a reference for further fundamental research by outlining the primary active ingredients and putative molecular mechanisms of SWD in the treatment of CRA.

Exploring the mechanism of Guizhi decoction’s“Jun-Chen-Zuo-Shi”in treating plant nervous disorders based on weighted network pharmacology and molecular docking techniques

Objective:To explore the mechanism of Guizhi decoction’s“Jun-Chen-Zuo-Shi”in treating plant nervous disorders based on network pharmacology and molecular docking methods.Methods:The main active ingredients of Guizhi decoction were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and plant nervous disorder-related targets were screened from the Gene Cards database,OMIM database,and PharmGKB database.The intersection of the two was obtained.The intersection targets were used to draw a protein interaction network and a“Traditional Chinese Medicine-active ingredient-target”network using the STRING database and Cytoscape 3.9.1.The nodes in the“Traditional Chinese Medicine-active ingredient-target”network were weighted according to the“Jun-Chen-Zuo-Shi”principle.Kyoto Encyclopedia of Genes and Genomes,and gene ontology enrichment analysis were performed on the intersection targets.Molecular docking was used to verify the affinity between core targets and key ingredients.Results:A total of 225 effective components of Guizhi decoction were screened,among which 127 components could bind to 160 common targets and play a therapeutic role.The common targets were mainly enriched in 2785 gene ontology entries and 189 Kyoto Encyclopedia of Genes and Genomes pathways.Molecular docking confirmed that core targets could spontaneously bind to key ingredients.Conclusion:The key targets for the treatment of plant nervous disorders by Guizhi decoction are MAPK1,TP53,RB1,STAT3,MAPK3,MAPK14,etc.,which reflect the characteristics of the synergistic mechanism of traditional Chinese medicine with multiple components,targets,and pathways through the regulation of inflammatory signal pathways and oxidative stress processes.

The active mechanism of the Sheng Yang San Huo decoction on diabetic peripheral neuropathy on network pharmacology

Objectives:To discuss the mechanism of Sheng Yang San Huo decoction on diabetic peripheral neuropathy using the network pharmacology method.Methods:The BATMAN-TCM database,TCM-ID database,Chinese Natural Product Chemical Composition Database,and TCMIP database were employed to screen the chemical active ingredients of each herb in Sheng Yang San Huo decoction based on the“Libinsky Drug Rules”.SwissTargetPrediction was used to screen effective action targets for each herb in the prescription.Additionally,Cytoscape 3.7.0 was utilized to construct a“drug-target”network.GeneCards,OMIM,and MaLaCards databases were utilized to gather targets related to diabetic peripheral neuropathy.VENNY 2.1 online platform was employed to match drug and disease targets,draw a Venn diagram,and construct a“drug-active compounds-common target”network using Cytoscape 3.7.0.gene ontology biological process analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the targets were conducted using the DAVID 6.8 database.Enrichment analysis results were visualized using the OmicShareTool online platform.Molecular docking was performed using CB-Dock2.Results:Following screening,a total of 217 active compounds and 132 potential targets were identified in Sheng Yang San Huo decoction.The effects are primarily enriched in pathways such as Lipid and Atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,and the IL-17 signaling pathway.The binding energy of the key active ingredients to the core protein targets of DPN was favorable.Conclusion:The study reveals the characteristics of multiple targets and pathways of Sheng Yang San Huo decoction,providing new insights for the clinical application of this prescription.

Network Pharmacology Research of Qingyi Decoction(清胰汤)in the Treatment of Acute Pancreatitis

Presently,clinically specific drugs are absent for acute pancreatitis(AP).Numerous clinical investigations have extolled the notable efficacy of Qingyi Decoction(QYD,清胰汤)in the management of AP.However,the molecular mechanisms are lacking.Therefore,we analyzed pharmacological mechanisms of QYD in treating AP through network pharmacology.As for the network pharmacology,173active compounds and 1,073 active target genes for QYD were identified.Of these,884 active target genes correlated with AP among the 11128 AP-associated genes and were linked to the 173 active compounds.In addition,GO functional enrichment and KEGG pathway enrichment revealed that these target genes were mainly enriched in cancer signaling,neuroactive ligand-receptor interactions,lipids and atherosclerosis,cAMP signaling,central carbon metabolism in cancer,and calcium signaling pathways.Finally,molecular docking was employed to assess the binding affinity between target proteins and their associated compounds.This study identified critical compounds and potential target genes.Our study may serve as a foundation for subsequent investigations on the therapeutic potential of QYD in treating AP.

Exploring the mechanism of action of Wuzhuyu Decoction for vascular headache based on network pharmacology and molecular docking

Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.

Identifying medication regularity of traditional Chinese medicine and potential pharmacological mechanism of Jiedu Sangen decoction in colorectal cancer treatment by data mining and network pharmacology

Objective:Colorectal cancer(CRC)is one of the most common malignancies in the world,and traditional Chinese medicine(TCM)is widely used in its treatment in China.However,the medication rules of TCM for CRC treatment remain unclear.Therefore,data mining combined with network pharmacology was utilized to establish treatment principles and rules.Methods:The CRC cases treated at Zhejiang Provincial Hospital of Chinese Medicine from January 1,2016 to October 31,2021 were analyzed using data mining methods.UPLC-Q/TOF-MS analysis was performed to identify the chemical composition of Jiedu Sangen decoction(JSD).Network pharmacology was used to reveal the therapeutic mechanism of JSD.Results:A total of 312 cases 2,998 prescriptions that met the inclusion criteria used 343 kinds of traditional Chinese medicines.The nature of the herbs used in treatment was mainly warm and mild.The taste was mainly sweet,bitter,and pungent.The meridian tropisms were mainly the spleen meridian,followed by lung and stomach meridians.Tonifying and replenishing herbs were the most frequently used in treatment.High-frequency herbs were classified into 11 categories by cluster analysis,and 42 association rules were obtained by association rule analysis.Combined with complex network analysis,3 core prescriptions for clinical CRC treatment were obtained.Jiedu Sangen decoction contains 64 chemical ingredients,out of which 31 active ingredients were identified,including polydatin,caffeic acid,and glutamic acid,along with 130 potential targets such as AKT1,SRC,and MAPK1.Jiedu Sangen decoction may play a role in regulating inflammation,immunity,metabolism,and hormones in the development of CRC via pathways such as the relaxin signaling pathway,IL-17 signaling pathway,prolactin signaling pathway,and T cell receptor signaling pathway.Conclusions:This study summarizes the treatment and medication principles for clinical CRC treatment,promoting the inheritance and development of the traditional Chinese medical experience.

Analysis of the effect of Bupleurum on fever in Xiaochaihu Decoction based on network pharmacology

Objective:To explore the mechanism of Bupleurum on fever by means of network pharmacology,and to provide ideas for further experimental study.Methods:The effective components and targets of Xiaochaihu Decoction and Bupleurum were extracted by searching TCM systematic pharmacology database(TCMSP),and got to the effective components and targets of Xiaochaihu Decoction.By searching GeneCards database,disGeNET database,OMIM database and symmap database to extract the disease target of fever.And the"protein interaction network"was constructed with the protein interaction relationship in HINT database as the background network,and the GO enrichment analysis and KEGG pathway enrichment analysis were carried out on the targets by using R software and DAVID database.Results:726 kinds of effective components of Xiaochaihu Decoction were obtained from TCMSP database,including 215 kinds of effective components of Bupleurum,677 targets of Xiaochaihu Decoction and 516 targets of Bupleurum.A total of 7305 fever-related genes were obtained from the disease database,and 400 key targets of Bupleurum for fever treatment were obtained by mapping drug targets and disease targets GAPDH,AKT1,INS,IL-6 and VEGFA,are the targets with high node connectivity in PPI network.The results of GO enrichment of key targets by R software are cofactor binding and coenzyme binding.KEGG enrichment pathway of key targets involves infection,cancer,immune system diseases and so on.Conclusion:This study preliminarily verified the effect and mechanism of Bupleurum on fever,and provided reference for further study.

A systematic study of Erzhu Erchen decoction against damp-heat internalized type 2 diabetes based on data mining and experimental verification

Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized disease.Nevertheless,the mechanism of EZECD on damp-heat internalized Type 2 diabetes(T2D)remains unknown.We employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized T2D.Methods:The main compounds or genes of EZECD and damp-heat internalized T2D were obtained from the pharmacology databases.Succeeding,the overlapped targets of EZECD and damp-heat internalized T2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes analysis.And the compound-disease targets-pathway network were constructed to obtain the hub compound.Moreover,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock 1.5.7.Furthermore,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized T2D.Finally,the interactions of hub compound and genes were explored using Comparative Toxicogenomics Database and quantitative polymerase chain reaction.Results:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized T2D could be quercetin.Consistently,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network analysis.Molecular docking showed that quercetin could bind with the hub genes.Further,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the TNF or lipopolysaccharide process,and AHR or CCL2 positively regulated lipid and atherosclerosis,and/or including NOD-like receptor signaling pathway,and TNF signaling pathway.Ultimately,the quantitative polymerase chain reaction and western blotting analysis showed that quercetin could down-regulated the mRNA and protein experssion of CASP8,CCL2,and AHR.It was consistent with the results in Comparative Toxicogenomics Database databases.Conclusion:These results demonstrated quercetin could inhibit the expression of CASP8,CCL2,AHR in damp-heat internalized T2D,which improves insulin secretion and inhibits lipid and atherosclerosis,as well as/or including NOD-like receptor signaling pathway,and TNF signaling pathway,suggesting that EZECD may be more effective to treat damp-heat internalized T2D.