The natural alkaloids extracted from Chinese herbal medicine have shown high medicinal value in vivo and in vitro, such as bacteriostasis, anti-virus, anti-tumor and anti-inflammation. This paper focuses on matrine an...The natural alkaloids extracted from Chinese herbal medicine have shown high medicinal value in vivo and in vitro, such as bacteriostasis, anti-virus, anti-tumor and anti-inflammation. This paper focuses on matrine and reviews its action mechanism and toxicological action. It is concluded that the medicinal prospect of matrine is very broad, but more basic research and clinical trials are needed for more comprehensive evaluation.展开更多
The role of the autopsy: 1) Whether the death is ascribable to a natural or unnatural cause and when natural, if cardiac or extra-cardiac;2) The nosology of the cardiac diseases and the mechanism of cardiac death, whe...The role of the autopsy: 1) Whether the death is ascribable to a natural or unnatural cause and when natural, if cardiac or extra-cardiac;2) The nosology of the cardiac diseases and the mechanism of cardiac death, whether arrhythmic or mechanical;3) If the cardiac disease is inherited, screening and counselling of the next of kin is required. About 30% of sudden deaths is ascribable to genetically determined morbid entities, mostly transmissible with the autosomal dominant pattern of inheritance, so that 50% of the first degree relatives are genetically affected (“carriers”) and exposed at risk;4) If toxic or illicit drug abuse was involved.展开更多
In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cas...In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.展开更多
Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underl...Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.展开更多
BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal ...BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.展开更多
BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,...BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.展开更多
Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum ph...Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.展开更多
[Objectives]To investigate the mechanism of action of glyasperin A(GAA)in intervening menopause using network pharmacology and molecular docking technology.[Methods]All target names of the active ingredients were scre...[Objectives]To investigate the mechanism of action of glyasperin A(GAA)in intervening menopause using network pharmacology and molecular docking technology.[Methods]All target names of the active ingredients were screened using TCMSP,3D model molecules converted into SMILES online tool,Swiss target prediction and literature search.The relevant target genes corresponding to menopause were identified using the Genecards database.Venn 2.1.0 was then used to generate the corresponding Venn diagram.Finally,the protein-protein interaction(PPI)network was constructed using Cytoscape 3.9.1 software.The core targets that were screened underwent enrichment and analysis using the Gene Ontology(GO)biological process and KEGG pathways with the assistance of the DAVID database and bioinformatics.The molecular docking was then verified using AutoDock and Pymol software on the core targets.[Results]This study screened 100 target genes of active ingredients.In the PPI network,ESR1 and AKT1 were found to have a higher degree.The GO and KEGG enrichment analyses revealed that the biological processes primarily involved platelet activation,regulation of circadian rhythms,and regulation of mRNA stability.The signalling pathways included hepatitis B,cytotoxicity,and gastric cancer.The molecular docking results indicated that the key active ingredients and proteins bound well,as evidenced by their small binding energies.[Conclusions]Using a systematic network pharmacology approach,this study predicts the basic pharmacological effects and potential mechanisms of GAA in intervening menopause,which provides a foundation for further research on its pharmacological mechanisms.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but...BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.展开更多
Objective: This study aims to investigate the potential targets of diosgenin for the treatment of Alzheimer's disease (AD) and Coronavirus Disease 2019 (COVID-19) through the utilization of bioinformatics, network...Objective: This study aims to investigate the potential targets of diosgenin for the treatment of Alzheimer's disease (AD) and Coronavirus Disease 2019 (COVID-19) through the utilization of bioinformatics, network pharmacology, and molecular docking techniques. Methods: Differential expression genes (DEGs) shared by AD and COVID-19 were enriched by bioinformatics. Additionally, regulatory networks were analyzed to identify key genes in the Transcription Factor (TF) of both diseases. The networks were visualized using Cytoscape. Utilizing the DGIdb database, an investigation was conducted to identify potential drugs capable of treating both Alzheimer's disease (AD) and COVID-19. Subsequently, a Venn diagram analysis was performed using the drugs associated with AD and COVID-19 in the CTD database, leading to the identification of diosgenin as a promising candidate for the treatment of both AD and COVID-19.SEA, SuperPred, Swiss Target Prediction and TCMSP were used to predict the target of diosgenin in the treatment of AD and COVID-19, and the target of diosgenin in the treatment of AD and COVID-19 was determined by Wayne diagram intersection analysis with the differentially expressed genes of AD and COVID- 19. Their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed jointly. Genomes The Protein Protein Interaction (PPI) network of these drug targets was constructed, and core targets with the highest correlation were screened out. The binding of diosgenin to these core targets was analyzed by molecular docking. Results: Through enrichment and cluster analysis, it was found that the biological processes, pathways and diseases enriched by DEGs in AD and COVID-19 were all related to inflammation and immune regulation. These common DEGs and Trust databases were used to construct AD and COVID-19 TFs regulatory networks. Diosgenin was predicted as a potential drug for the treatment of AD and COVID-19 by network pharmacology, and 36 targets of diosgenin for the treatment of AD and 27 targets for COVID-19 were revealed. The six core targets with the highest correlation were selected for molecular docking with diosgenin using CytohHubba to calculate the scores. Conclusions: This study firstly revealed that the common TFs regulatory network of AD and COVID-19, and predicted and verified diosgenin as a potential drug for the treatment of AD and COVID-19. The binding of diosgenin to the core pharmacological targets for the treatment of AD and COVID-19 was determined by molecular docking, which provides a theoretical basis for developing a new approach to clinical treatment of AD and COVID-19.展开更多
Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrha...Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage.This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment.Methods:Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension.Bioactive compounds related to BHD were screened,and relevant targets associated with hypertension and BHD were retrieved.Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores.Lastly,the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated.Results:Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress.Cell experiments further indicated the pivotal role of endothelial cells in hypertension,and validation analysis showed that BHD significantly preserved cell morphology,suppressed oxidative stress reactions,activated the PI3K/Akt/eNOS signaling pathways,preserved normal endothelial cell function,and reduced cell apoptosis.Conclusion:BHD effectively activates the PI3K/Akt/VEGF signaling pathway,attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels,and mitigates apoptosis,supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension.展开更多
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...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.展开更多
[Objectives]To explore the therapeutic effect of Polygonum capitatum on renal calculus in rats based on network pharmacology.[Methods]Through the preliminary construction of P.capitatum-urolithiasis disease target net...[Objectives]To explore the therapeutic effect of Polygonum capitatum on renal calculus in rats based on network pharmacology.[Methods]Through the preliminary construction of P.capitatum-urolithiasis disease target network,explore the active components,action pathway and action target of P.capitatum-urolithiasis treatment,and use 1%ethylene glycol+2%ammonium chloride to induce SD rat kidney calcium oxalate stone model to verify the efficacy of P.capitatum-urolithiasis treatment.[Results]Through the network pharmacological prediction,it is found that the important active components in P.capitatum were quercetin,gallic acid,rutin,silybin,catechin,kaempferol and so on;potential active targets include INS,CAT,IL-6,MOCOS,etc.The results also suggest that forkhead transcription factor signaling pathway(FoxO signaling pathway),tumor necrosis factor signaling pathway(TNF signaling pathway)and hypoxia-inducible factor signaling pathway(HIF-1 signaling pathway)are the core pathways.The results of biochemical indicators in animal experiment showed that the contents of serum urea nitrogen(BUN),creatinine(Cr)and malondialdehyde(MDA)in renal tissue in the treatment group(200,500 mg/kg)were significantly lower than those in the model group,while the content of superoxide dismutase(SOD)was significantly higher than that in the model group.In addition,the kidney tissue H&E staining sections showed that P.capitatum alcohol extract administration group rats kidney calcium oxalate crystals were significantly reduced compared with the model group,the degree of renal tubular lumen expansion was lighter than the model group,suggesting that P.capitatum alcohol extract has the effect of improving renal calculus in rats.[Conclusions]This study provides a theoretical reference for the deep development of P.capitatum in the treatment of renal calculus.展开更多
BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To in...BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.展开更多
BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be e...BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.展开更多
[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through n...[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through network pharmacological analysis,molecular docking simulation experiments and in vitro experiments,the main components and corresponding targets of Viola were screened out,and their anti-tumor signaling pathways were confirmed.MTT colorimetric assay was used to investigate the inhibitory effect of different extraction layers of Viola on the growth of tumor cells.[Results]18 anti-tumor active components such as 2α,19α-Dihydroxyursolic acid,Corlumine,Madolin U,Trifolirhizin and etc.,and 52 action targets such as PTGS2,PTGS1,P2RX7,MMP1,and GABRB3,and anti-tumor signaling pathways were confirmed.The results of molecular docking showed that all the selected Viola compounds had good binding activity.The results of MTT colorimetric assay showed that the petroleum ether layer and n-butanol layer had a good inhibitory effect on the growth of tumor cell lines.[Conclusions]Viola medicinal materials have the potential of anti-tumor,triterpenoids and flavonoids may be the main active components,and the petroleum ether layer and n-butanol layer have better inhibitory effect on the growth of tumor cells.展开更多
Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enter...Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.展开更多
Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sit...Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.展开更多
[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to ...[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO databases.The Chinese medicine compound-target network was constructed by Cytoscape software.Besides,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed.Afterward,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the databases.After the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating keloids.Hub genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling pathways.The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways.The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.展开更多
[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were...[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.展开更多
文摘The natural alkaloids extracted from Chinese herbal medicine have shown high medicinal value in vivo and in vitro, such as bacteriostasis, anti-virus, anti-tumor and anti-inflammation. This paper focuses on matrine and reviews its action mechanism and toxicological action. It is concluded that the medicinal prospect of matrine is very broad, but more basic research and clinical trials are needed for more comprehensive evaluation.
文摘The role of the autopsy: 1) Whether the death is ascribable to a natural or unnatural cause and when natural, if cardiac or extra-cardiac;2) The nosology of the cardiac diseases and the mechanism of cardiac death, whether arrhythmic or mechanical;3) If the cardiac disease is inherited, screening and counselling of the next of kin is required. About 30% of sudden deaths is ascribable to genetically determined morbid entities, mostly transmissible with the autosomal dominant pattern of inheritance, so that 50% of the first degree relatives are genetically affected (“carriers”) and exposed at risk;4) If toxic or illicit drug abuse was involved.
文摘In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.
文摘Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.
基金Natural Science Foundation of Hebei Province,No.H2018307071Traditional Chinese Medicine Research Plan Project in Hebei Province,No.2022122Hebei Provincial Science and Technology Program,No.17397763D.
文摘BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.
基金supported by the National Natural Science Foundation of China(82172182 and 82102311)Natural Science Foundation of Jiangsu Province(BK20211136)+2 种基金China Postdoctoral Science Foundation(2018M643890 and 2020M683718)Xuzhou Science and Technology Project(KC21215 and KC22136)Development Fund Project of Affiliated Hospital of Xuzhou Medical University(XYFY202232)。
文摘BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.
基金supported by Key R&D Project in Shandong ProvinceChina(Grant number:2020CXGC010505)+2 种基金Qingdao Science and Technology Demonstration Program for the Benefit of the PeopleShandong ProvinceChina(Grant number:23-7-8-smjk-3-nsh)。
文摘Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.
基金Supported by Project of Science and Technology Department of Guizhou Province ([2019]1401)Guizhou Administration of Traditional Chinese Medicine (QZYY-2021-03)Guizhou Provincial Health Commission (gzwkj2021-464).
文摘[Objectives]To investigate the mechanism of action of glyasperin A(GAA)in intervening menopause using network pharmacology and molecular docking technology.[Methods]All target names of the active ingredients were screened using TCMSP,3D model molecules converted into SMILES online tool,Swiss target prediction and literature search.The relevant target genes corresponding to menopause were identified using the Genecards database.Venn 2.1.0 was then used to generate the corresponding Venn diagram.Finally,the protein-protein interaction(PPI)network was constructed using Cytoscape 3.9.1 software.The core targets that were screened underwent enrichment and analysis using the Gene Ontology(GO)biological process and KEGG pathways with the assistance of the DAVID database and bioinformatics.The molecular docking was then verified using AutoDock and Pymol software on the core targets.[Results]This study screened 100 target genes of active ingredients.In the PPI network,ESR1 and AKT1 were found to have a higher degree.The GO and KEGG enrichment analyses revealed that the biological processes primarily involved platelet activation,regulation of circadian rhythms,and regulation of mRNA stability.The signalling pathways included hepatitis B,cytotoxicity,and gastric cancer.The molecular docking results indicated that the key active ingredients and proteins bound well,as evidenced by their small binding energies.[Conclusions]Using a systematic network pharmacology approach,this study predicts the basic pharmacological effects and potential mechanisms of GAA in intervening menopause,which provides a foundation for further research on its pharmacological mechanisms.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.
基金Research and Development and Industrialization Demonstration of Xinjiang Special Medicinal Materials,Antiinfective Drugs and Disinfection Products-Construction of Xinjiang Special Resource Antiinfective Drug Research and Development Platform(No.2021A03002-4)。
文摘Objective: This study aims to investigate the potential targets of diosgenin for the treatment of Alzheimer's disease (AD) and Coronavirus Disease 2019 (COVID-19) through the utilization of bioinformatics, network pharmacology, and molecular docking techniques. Methods: Differential expression genes (DEGs) shared by AD and COVID-19 were enriched by bioinformatics. Additionally, regulatory networks were analyzed to identify key genes in the Transcription Factor (TF) of both diseases. The networks were visualized using Cytoscape. Utilizing the DGIdb database, an investigation was conducted to identify potential drugs capable of treating both Alzheimer's disease (AD) and COVID-19. Subsequently, a Venn diagram analysis was performed using the drugs associated with AD and COVID-19 in the CTD database, leading to the identification of diosgenin as a promising candidate for the treatment of both AD and COVID-19.SEA, SuperPred, Swiss Target Prediction and TCMSP were used to predict the target of diosgenin in the treatment of AD and COVID-19, and the target of diosgenin in the treatment of AD and COVID-19 was determined by Wayne diagram intersection analysis with the differentially expressed genes of AD and COVID- 19. Their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed jointly. Genomes The Protein Protein Interaction (PPI) network of these drug targets was constructed, and core targets with the highest correlation were screened out. The binding of diosgenin to these core targets was analyzed by molecular docking. Results: Through enrichment and cluster analysis, it was found that the biological processes, pathways and diseases enriched by DEGs in AD and COVID-19 were all related to inflammation and immune regulation. These common DEGs and Trust databases were used to construct AD and COVID-19 TFs regulatory networks. Diosgenin was predicted as a potential drug for the treatment of AD and COVID-19 by network pharmacology, and 36 targets of diosgenin for the treatment of AD and 27 targets for COVID-19 were revealed. The six core targets with the highest correlation were selected for molecular docking with diosgenin using CytohHubba to calculate the scores. Conclusions: This study firstly revealed that the common TFs regulatory network of AD and COVID-19, and predicted and verified diosgenin as a potential drug for the treatment of AD and COVID-19. The binding of diosgenin to the core pharmacological targets for the treatment of AD and COVID-19 was determined by molecular docking, which provides a theoretical basis for developing a new approach to clinical treatment of AD and COVID-19.
基金the Liaoning Provincial Science and Technology Plan Project(2023-MSLH-178)the Project Fund of Liaoning Provincial Department of Education(LJKMZ20221315,L202025)+1 种基金the Special Fund of Liaoning Provincial Department of Science and Technology for Central Guidance of Local Science and Technology Development(2018416016)the Project Fund of Liaoning Provincial Department of Human Resources and Social Security"Millions of Talents Program"(2020921097).
文摘Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage.This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment.Methods:Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension.Bioactive compounds related to BHD were screened,and relevant targets associated with hypertension and BHD were retrieved.Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores.Lastly,the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated.Results:Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress.Cell experiments further indicated the pivotal role of endothelial cells in hypertension,and validation analysis showed that BHD significantly preserved cell morphology,suppressed oxidative stress reactions,activated the PI3K/Akt/eNOS signaling pathways,preserved normal endothelial cell function,and reduced cell apoptosis.Conclusion:BHD effectively activates the PI3K/Akt/VEGF signaling pathway,attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels,and mitigates apoptosis,supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension.
基金supported by grants from the Special Project for Transformation of Scientific and Technological Achievements in Qinghai Province(No.2021-SF-150)the National Natural Science Foundation of China(No.82173929).
文摘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.
基金Supported by Guizhou Provincial Science and Technology Plan Project (Gui Qian He Ji Chu-ZK[2022]General 362)Guizhou Provincial Department of Education Science and Technology Achievement Transfer and Transformation Project (Gui Jiao Ji[2022]064)+2 种基金Guizhou Provincial Department of Education Higher Education Engineering Research Center (Gui Jiao Ji[2023]035)China National University Student Innovation&Entrepreneurship Development Program (202210660131&202310660082)Guizhou s Emerging University Think Tank Alliance Construction Project (Qian Jiao Zhe[2023]ZK01).
文摘[Objectives]To explore the therapeutic effect of Polygonum capitatum on renal calculus in rats based on network pharmacology.[Methods]Through the preliminary construction of P.capitatum-urolithiasis disease target network,explore the active components,action pathway and action target of P.capitatum-urolithiasis treatment,and use 1%ethylene glycol+2%ammonium chloride to induce SD rat kidney calcium oxalate stone model to verify the efficacy of P.capitatum-urolithiasis treatment.[Results]Through the network pharmacological prediction,it is found that the important active components in P.capitatum were quercetin,gallic acid,rutin,silybin,catechin,kaempferol and so on;potential active targets include INS,CAT,IL-6,MOCOS,etc.The results also suggest that forkhead transcription factor signaling pathway(FoxO signaling pathway),tumor necrosis factor signaling pathway(TNF signaling pathway)and hypoxia-inducible factor signaling pathway(HIF-1 signaling pathway)are the core pathways.The results of biochemical indicators in animal experiment showed that the contents of serum urea nitrogen(BUN),creatinine(Cr)and malondialdehyde(MDA)in renal tissue in the treatment group(200,500 mg/kg)were significantly lower than those in the model group,while the content of superoxide dismutase(SOD)was significantly higher than that in the model group.In addition,the kidney tissue H&E staining sections showed that P.capitatum alcohol extract administration group rats kidney calcium oxalate crystals were significantly reduced compared with the model group,the degree of renal tubular lumen expansion was lighter than the model group,suggesting that P.capitatum alcohol extract has the effect of improving renal calculus in rats.[Conclusions]This study provides a theoretical reference for the deep development of P.capitatum in the treatment of renal calculus.
基金Supported by Ningxia Science and Technology Benefiting People Program,No.2022CMG03064National Natural Science Foundation of China,No.82260879Ningxia Natural Science Foundation,No.2022AAC03144 and 2022AAC02039.
文摘BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.
基金Supported by the 2022 Shaoxing City Health Science and Technology Program(Health Science and Technology Program),No.2022KY050。
文摘BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.
基金Supported by the National Key Research and Development Plan (2018YFC1708005)Sichuan Provincial Natural Science Foundation (Young Scientist Fund Project-2022NSFSC1588)Leading Talent Support Plan of National Ethnic Affairs Commission in 2021,Double First-Class Initiative Project of Southwest Minzu University (CX2023054).
文摘[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through network pharmacological analysis,molecular docking simulation experiments and in vitro experiments,the main components and corresponding targets of Viola were screened out,and their anti-tumor signaling pathways were confirmed.MTT colorimetric assay was used to investigate the inhibitory effect of different extraction layers of Viola on the growth of tumor cells.[Results]18 anti-tumor active components such as 2α,19α-Dihydroxyursolic acid,Corlumine,Madolin U,Trifolirhizin and etc.,and 52 action targets such as PTGS2,PTGS1,P2RX7,MMP1,and GABRB3,and anti-tumor signaling pathways were confirmed.The results of molecular docking showed that all the selected Viola compounds had good binding activity.The results of MTT colorimetric assay showed that the petroleum ether layer and n-butanol layer had a good inhibitory effect on the growth of tumor cell lines.[Conclusions]Viola medicinal materials have the potential of anti-tumor,triterpenoids and flavonoids may be the main active components,and the petroleum ether layer and n-butanol layer have better inhibitory effect on the growth of tumor cells.
基金supported by National Science Fund for Young Scholars of China (Grant No.82204594).
文摘Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.
基金Emergency Research Project for Novel Coronavirus(2019-nCoV)Prevention and Control in Shanxi Province(No.202003D31012/GZ)Jingfang Fuyang Key Laboratory of Shanxi Province(No.202104010910011)Shanxi Provincial Health Commission Key Laboratory Construction Project。
文摘Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.
基金Supported by Central Government Funds of Guiding Local Scientific and Technological Development for Sichuan Province(2021ZYD0057).
文摘[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO databases.The Chinese medicine compound-target network was constructed by Cytoscape software.Besides,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed.Afterward,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the databases.After the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating keloids.Hub genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling pathways.The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways.The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.
基金Supported by Project of Science and Technology Department of Guizhou Province([2019]1401ZK[2021]-546)Guizhou Provincial Health Commission(gzwkj2021-464)。
文摘[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.