Active components of Bupleuri Radix in the treatment of schizophrenia analyzed by network pharmacology and clinical verification

Background:Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine.Currently,the therapeutic effect of treating schizophrenia is relatively well understood.However,there are fewer studies examining the underlying mechanisms of its treatment.The objective of the study was to investigate the primary mechanisms of Bupleuri Radix in treating schizophrenia through network pharmacology and clinical validation.Method:Network pharmacology revealed possible molecular mechanisms,followed by clinical verification.Sixty-seven schizophrenia patients undergoing treatment at the Hunan Brain Hospital between October and November 2022 were recruited and randomly divided into the olanzapine group and the olanzapine+Bupleuri Radix group.Additionally,32 healthy people undergoing physical examinations during the same period were included as the control group.The patient’s positive and negative symptom scale scores were compared.qPCR was used to detect the mRNA expression levels of ESR1,mTOR,EIF4E,and SMAD4 in peripheral blood.Results:Through network pharmacological analysis,it was concluded in this study that Bupleuri Radix might regulate the mTOR,PI3K-Akt,and HIF-1 signaling pathways.Clinical experiments indicated that compared with before treatment,the positive and negative symptom scale scores and total scores of the two treatment groups were significantly decreased after treatment(P<0.01).In addition,the positive and negative symptom scale scores and total scores in the olanzapine+Bupleuri Radix group were significantly decreased(P<0.01)compared to the olanzapine group after treatment.Before treatment,ESR1 mRNA expression levels in peripheral blood were significantly higher in the two treatment groups than in the control group,whereas the mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly lower(P<0.01).The mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly higher after therapy than before treatment,whereas the mRNA expression levels of ESR1 in peripheral blood were significantly lower(P<0.01).After therapy,the olanzapine+Bupleuri Radix group’s mRNA expression levels of mTOR,EIF4E,and SMAD4 were significantly higher than those of the olanzapine group,whereas the mRNA expression levels of ESR1 were significantly lower(P<0.01).Conclusion:The mechanism of Bupleuri Radix’s therapeutic efficacy in schizophrenia may involve the up-regulation of mTOR,EIF4E,and SMAD4 mRNA expression and the down-regulation of ESR1 mRNA expression in peripheral blood.

PREDICTION OF THE THERAPEUTIC EFFECTIVENESS OF NEW DRUGS FROM CLINICAL PHARMACOLOGY STUDIES

The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-

Pediatric Clinical Pharmacology and Child Health:A Canadian Perspective

Introduction Canadian academic centres and children’s hospitals have had a longstanding interest in the improvement of drug therapy for children through research conducted across the four pillars of activity identified as being of

Systems pharmacology modeling in neuroscience: Prediction and outcome of PF-04995274, a 5-HT4 partial agonist, in a clinical scopolamine impairment trial

Background: 5-HT4receptors in cortex and hippocampus area are considered as a possible target for modulation of cognitive functions in Alzheimer’s disease (AD). A systems pharmacology approach was adopted to evaluate the potential of the 5-HT4 modulation in providing beneficialeffects on cognition in AD. Methods: A serotonergic synaptic cleft model was developed by integrating serotonin firing, release, synaptic half-life, drug/tracer properties (affinity and agonism) as inputs and5-HT4 activity as output. The serotonergic model was calibrated using bothinvivo data on free 5-HT levels in preclinical models and human imaging data. The model was further expanded to other neurontransmitter systems and incorporated into a computer-based cortical network model which implemented the physiology of 12 different membrane CNS targets. A biophysically realistic, multi-compartment model of 80 pyramidal cells and 40 interneurons was further calibrated usingdata reported for working memory tasks in healthyhumans and schizophrenia patients. Model output was the duration of the network firing activity in response to an external stimulus. Alzheimer’s disease (AD) pathology, in particular synapse and neuronal cell loss in addition to cholinergic deficits, was calibrated to align with the natural clinical disease progression. The model was used to provide insights into the effect of 5-HT4 activation on working memory and to prospectively simulate the response of PF- 04995274, a 5-HT4partial agonist, in a scopolamine-reversal trial in healthy human subjects. Results: The model output suggested a beneficial effect of 5-HT4 agonism on working memory. The model also projected no effect or an exacerbation of scopolamine impairment for low in- trinsic activity 5-HT4agonists, which was supported by the subsequent human trial outcome. The clinical prediction of the disease model strongly suggests that 5-HT4 agonists with high intrinsic activity may have a beneficial effect on cognition in AD patients.

Teaching Clinical Pharmacology to Undergraduate Nursing Students: Barriers and Strategies

This study examined perceived learning barriers to and strategies for teaching clinical pharmacology to undergraduate nursing students. The purposes of this study were to discuss barriers and strategies for teaching clinical pharmacology to undergraduate nursing students and compare those findings to student evaluation responses. This study used a comparative, cross-sectional design and examined data from nursing faculty who had taught pharmacology and from student evaluations over the past five years to compare perceived barriers and strategies. Several barriers were identified, including content saturation, course placement, English as a second language, and resources. Effective teaching strategies identified were lectures, teaching by drug class, reviewing pathophysiology, and case studies. Students’ evaluations revealed that students found that the course content was substantial and felt that the textbook did not fully demonstrate nursing considerations. Other answers were nonspecific. Using these strategies is critical to effectively deliver pharmacological material and to foster understanding among undergraduate students. Faculty members agree that having pharmacological concepts threaded throughout the curriculum increases students’ knowledge of medications and medication management. Additional creative approaches to teaching clinical pharmacology to undergraduate nursing students are needed.

Research on the mechanism of Chaihu Huangqin medicine based on integrated pharmacology to improve the clinical symptoms of COVID-19

Objective:Novel coronavirus(COVID-19)was used to improve the clinical symptoms of the new type coronavirus(LV),based on integrated pharmacology.Methods:TCMIP v2.0 was used to predict the key target and action pathway of Bupleurum baicalensis Georgi in improving the clinical symptoms of covid-19.The multi-dimensional network diagram of"drug pair active component key target action pathway"was drawn to explore its action mechanism from the molecular level.Results:Bupleurum and Scutellaria baicalensis could regulate IL signaling pathway and clec7a(a member of C-type lectin domain 7 family)/Inflammatory pathway,immune stress and other related signaling pathways can inhibit activated cytokines,alleviate excessive immune response,eliminate inflammation,and resist virus.In addition,the core targets of Bupleurum baicalensis baicalensis Georgi:nuclear factor kB(NFKB2,NFKB1),interleukin(IL-6,IL-1B),toll like receptor 4(TLR4),tumor necrosis factor(TNF)and so on are mostly induced by inflammation It is related to body damage.Bupleurum and scutellaria have the clinical effects of anti-inflammatory,antiviral,strengthening immunity,inhibiting pulmonary fibrosis and so on.Conclusion:Radix Bupleuri Scutellariae can be used to treat covid-19 by multi-channel,multi-target and multi ring.The results of this study provide a theoretical basis for Bupleurum Scutellaria to improve the use of COVID-19.

Mechanism of Liangxue Huayu decoction in treatment of age-related macular degeneration based on network pharmacology and clinical validation

Background:This paper investigates the mechanism of Liangxue Huayu decoction treating age-related macular degeneration through network pharmacology and clinical verification.Methods:The potential targets of Liangxue Huayu decoction were retrieved by the BATMAN-TCM database,and age-related macular degeneration-related disease targets were collected using the OMIM,GeneCards,and CTD databases.The intersection of targets for Liangxue Huayu decoction for age-related macular degeneration was performed using the online tool Venny2.1.0.Protein-protein interaction network was drawn using the String database.And core targets were obtained with the CytoNCA plugin.The gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape database.Finally,targets of Liangxue Huayu decoction for age-related macular degeneration were identified in clinical research.Results:In this study,832 potential action targets and 9,475 age-related macular degeneration-related disease targets were screened,and 575 intersection targets of Liangxue Huayu decoction and age-related macular degeneration were obtained.Protein-protein interaction network analysis showed that 15 core targets include chemokine 8,interleukin 1,histone deacetylase 2,estrogen receptor 2,and glutamate ionotropic receptor NMDA type subunit 1,et al.Gene ontology enrichment analysis included 2,727 biological processes,434 molecular functions,and 206 cellular components.Kyoto Encyclopedia of Genes and Genomes enrichment analysis selected 107 signaling pathways.Clinical validation showed that peripheral blood chemokine 8 and interleukin 1 levels were significantly lower after age-related macular degeneration patients compared with before treatment,and the difference was statistically significant(t chemokine 8=12.684,t interleukin 1=11.405,all P<0.001).Conclusion:By treating age-related macular degeneration with multiple targets and multiple pathways,Liangxue Huayu decoction can down-regulate the expression of inflammatory factors and treat age-related macular degeneration,which provides a basis for further studying the action mechanism of regulating age-related macular degeneration.

Research progress of Sini decoction in pharmacy, pharmacology and clinical application

Sini decoction originated from Zhang Zhongjing's Treatise on Cold Pathogenic and Miscellaneous Diseases(200-210 C.E.)in the Eastern Han Dynasty.It is a traditional and famous prescription in China.Its preparations mainly include Sini decoction,Sini decoction drop pills and Sini decoction suppositories.The main chemical components are diterpenoid alkaloids,gingerol,volatile oil,coumarin,polysaccharide,triterpene saponins,flavonoids,amino acids,and alkaloids.This product has a cardiovascular function,anti-shock,anti-diabetes complications,anti-tumor,anti-atherosclerosis,and effects on the nervous system.Modern clinical practice is widely used in cardiovascular,respiratory,digestive,neurological and gynecological diseases.This paper reviews the pharmaceutical research,pharmacological effects,safety evaluation and clinical application of Sini decoction,including the source and composition of Sini decoction,the origin and resource status of authentic medicinal materials of Sini decoction,the research on preparation form reform,chemical composition and quality control,to provide a reference for further research and clinical promotion of Sini decoction.

Efficacy of Tounongsan decoction(透脓散方)on pyogenic liver abscess:network pharmacology and clinical trial validation

OBJECTIVE:To elucidate the molecular mechanisms governing the effect of Tounongsan decoction(透脓散方,TNS)on the pyogenic liver abscess.METHODS:Based on oral bioavailability and druglikeness,the main active components of TNS were screened using the Traditional Chinese Medicine Systems Pharmacology platform.The Gene Card and Uni Prot databases were used to establish a database of pyogenic liver abscess targets.The interactive network map of drug-ingredients-target-disease was constructed using Cytoscape software(Version 3.7.2).A proteinprotein interaction network was constructed using the STRING database,and the related protein interaction relationships were analyzed.biological process of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for the core targets.Finally,a clinical trial was performed to verify the reliability of the network pharmacology.RESULTS:Forty active components of TNS decoction were obtained,and 61 potential targets and 11 proteins were identified.Pathways involved in the treatment of pyogenic liver abscess include the phosphatidylinositide 3-kinases-protein kinase B(PI3K-AKT),advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE),and tumor necrosis factor(TNF)signaling pathways.The results of network pharmacology analysis combined with clinical trials validated that TNS decoction could alleviate the inflammatory response of pyogenic liver abscesses by decreasing interleukin 6(IL-6)levels.CONCLUSIONS:TNS decoction has the characteristics of being multi-system,multi-component,and multi-target.Active ingredients in TNS,such as quercetin,kaempferol,fisetin,andβ-sitosterol,have strong potential to be candidate drugs for treating pyogenic liver abscesses.The possible mechanism of TSN decoction includes regulating immune and inflammatory responses and reducing IL-6 production to control inflammatory development.

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.

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.

Comparative analysis of breast and lung cancer survival rates and clinical trial enrollments among rural and urban patients in Georgia

Objectives:Rural patients have poor cancer outcomes and clinical trial(CT)enrollment compared to urban patients due to attitudinal,awareness,and healthcare access differential.Knowledge of cancer survival disparities and CT enrollment is important for designing interventions and innovative approaches to address the stated barriers.The study explores the potential disparities in cancer survival rates and clinical trial enrollments in rural and urban breast and lung cancer patients.Our hypotheses are that for both cancer types,urban cancer patients will have longer 5-year survival rates and higher enrollment rates in clinical trials than those in rural counties.Methods:We compared breast and lung cancer patients’survival rates and enrollment ratios in clinical trials between rural(RUCC 4-9)and urban counties in Georgia at a Comprehensive Cancer Center(CCC).To assess these differences,we carried out a series of independent samples t-tests and Chi-Square tests.Results:The outcomes indicate comparable 5-year survival rates across rural and urban counties for breast and lung cancer patients,failing to substantiate our hypothesis.While clinical trial enrollment rates demonstrated a significant difference between breast and lung cancer patients at CCC,no significant variation was observed based on rural or urban classification.Conclusion:These findings underscore the need for further research into the representation of rural patients with diverse cancer types at CCC and other cancer centers.Further,the findings have considerable implications for the initiation of positive social change to improve CT participation and reduce cancer survival disparities.

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.