Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by sevoflurane.Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.

Effects of sevoflurane on left ventricular function by speckletracking echocardiography in coronary bypass patients: A randomized trial

The present study aimed to dynamically observe the segmental and global myocardial movements of the left ventricle during coronary artery bypass grafting by transesophageal speckle-tracking echocardiography,and to assess the effect of sevoflurane on cardiac function.Sixty-four patients scheduled for the off-pump coronary artery bypass grafting were randomly divided into a sevoflurane-based anesthesia(AS)group and a propofolbased total intravenous anesthesia(AA)group.The AS group demonstrated a higher absolute value of left ventricular global longitudinal strain than that of the AA group at both T1(after harvesting all grafts and before coronary anastomosis)and T_(2)(30 min after completing all coronary anastomoses)(P<0.05).Moreover,strain improvement in the segment with the highest preoperative strain was significantly reduced in the AS group,compared with the AA group at both T1 and T_(2)(P<0.01).The flow of the left internal mammary artery-left anterior descending artery graft was superior,and the postoperative concentration of troponin T decreased rapidly in the AS group,compared with the AA group(P<0.05).Compared with total intravenous anesthesia,sevoflurane resulted in a significantly higher global longitudinal strain,stroke volume,and cardiac output.Sevoflurane also led to an amelioration in the condition of the arterial graft.Furthermore,sevoflurane significantly reduced strain improvement in the segmental myocardium with a high preoperative strain value.The findings need to be replicated in larger studies.

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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.

Impact of propofol and sevoflurane anesthesia on cognition and emotion in gastric cancer patients undergoing radical resection

BACKGROUND Propofol and sevoflurane are commonly used anesthetic agents for maintenance anesthesia during radical resection of gastric cancer.However,there is a debate concerning their differential effects on cognitive function,anxiety,and depression in patients undergoing this procedure.AIM To compare the effects of propofol and sevoflurane anesthesia on postoperative cognitive function,anxiety,depression,and organ function in patients undergoing radical resection of gastric cancer.METHODS A total of 80 patients were involved in this research.The subjects were divided into two groups:Propofol group and sevoflurane group.The evaluation scale for cognitive function was the Loewenstein occupational therapy cognitive assessment(LOTCA),and anxiety and depression were assessed with the aid of the self-rating anxiety scale(SAS)and self-rating depression scale(SDS).Hemodynamic indicators,oxidative stress levels,and pulmonary function were also measured.RESULTS The LOTCA score at 1 d after surgery was significantly lower in the propofol group than in the sevoflurane group.Additionally,the SAS and SDS scores of the sevoflurane group were significantly lower than those of the propofol group.The sevoflurane group showed greater stability in heart rate as well as the mean arterial pressure compared to the propofol group.Moreover,the sevoflurane group displayed better pulmonary function and less lung injury than the propofol group.CONCLUSION Both propofol and sevoflurane could be utilized as maintenance anesthesia during radical resection of gastric cancer.Propofol anesthesia has a minimal effect on patients'pulmonary function,consequently enhancing their postoperative recovery.Sevoflurane anesthesia causes less impairment on patients'cognitive function and mitigates negative emotions,leading to an improved postoperative mental state.Therefore,the selection of anesthetic agents should be based on the individual patient's specific circumstances.

The Mechanism of Celastrol in the Treatment of Metastatic Lung Adenocarcinoma Revealed by Network Pharmacology and Molecular Docking

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.

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

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.

Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

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.

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

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.

Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments

BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

Exploring the Mechanism of Action of Glyasperin A in Intervening Menopause Based on Network Pharmacology and Molecular Docking Technology

[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.

Analyzing the potential mechanism of Buyang Huanwu decoction for the treatment of salt-sensitive hypertension based on network pharmacology and in vivo experiments

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.

Using Network Pharmacology to Explore Therapeutic Effect of Polygonum capitatum on Renal Calculus in Rats

[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.

Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification

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.

Bioinformatics and network pharmacology identify the therapeutic role and potential targets of diosgenin in Alzheimer disease and COVID-19

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.

Systematic investigation of Radix Salviae for treating diabetic peripheral neuropathy disease based on network Pharmacology

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.

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking

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.

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.

Network pharmacology combined with molecular docking revealed the potential targets of Coridius chinensis in prostate cancer treatment

BACKGROUND Prostate cancer(PCa)has high morbidity and mortality rates in elderly men.With a history of thousands of years,traditional Chinese medicine derived from insects could be an important source for developing cancer-targeted drugs to prevent tumorigenesis,enhance therapeutic effects,and reduce the risk of recurrence and metastasis.Multiple studies have shown that Coridius chinensis(Cc)has anticancer effects.AIM To elucidate the mechanism of action of Cc against PCa via network pharma-cology and molecular docking.METHODS Potential targets for Cc and PCa were predicted using ChemDraw 19.0 software,the PharmMapper database and the GeneCards database.Then,the STRING database was used to construct the protein–protein interaction network.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment and molecular docking analyses were subsequently conducted to identify the key targets,active ingredients and pathways involved.RESULTS GO and KEGG analyses indicated that the PI3K-Akt signalling pathway was the critical pathway(P value<1.0×10-8).Multiple targeting ingredients that can affect multiple pathways in PCa have been identified in Cc.Seven active compounds(asponguanosines A,asponguanine B,asponguanine C,aspong-pyrazine A,N-acetyldopamine,aspongadenine B and aspongpyrazine B)were selected for molecular docking with 9 potential targets,and the results revealed that aspongpyrazine A and asponguanosine A are the main components by which Cc affects PCa(affinity<-5 kcal/mol,hydrogen bonding),but more studies are needed.CONCLUSION We used network pharmacology to predict the bioactive components and important targets of Cc for the treatment of PCa,supporting the development of Cc as a natural anticancer agent.

Exploring the Mechanism of Action of Gastrodin in Parkinson s Disease Based on Network Pharmacology

[Objectives]To explore the mechanism of action of gastrodin in the treatment of Parkinson s disease(PD)by employing network pharmacology technology,and to provide a scientific theoretical basis for the rational clinical application of gastrodin.[Methods]The target of gastrodin was identified through a search of the SwissTargetPrediction database.The keyword"Parkinson Disease"was employed to identify the pertinent targets of PD in the GeneCards and OMIM databases.The relationship between gastrodin and PD was elucidated,and a Veen map was constructed to identify the genes that were common to both.A total of 52 common drug targets associated with PD as identified in the Wayne chart were imported into the String database(https://string-db.org/)for protein-protein interaction prediction.Subsequently,Cytoscape 3.9.1 software was employed to construct a"drug-target"network.The potential targets of gastrodin in the treatment of PD were then imported into the DAVID database,where GO analysis and KEGG enrichment results were obtained.[Results]A total of 22 core targets and 53 related pathways of gastrodin were identified as potentially beneficial for the treatment of PD.[Conclusions]Gastrodin may be a potential therapeutic agent for the treatment of PD by modulating the biological process of apoptosis,affecting the relevant pathways such as the IL-17 signaling pathway and the TNF signaling pathway,and acting on GAPDH,EGFR,CASP3,MMP9 and other targets.

Potential pharmacological mechanisms of digallate in the treatment of enteritis based on network pharmacology and molecular docking

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.