The article concluded that network pharmacology provides new ideas and insights into the molecular mechanism of traditional Chinese medicine(TCM)treatment of cancer.TCM is a new choice and hot spot in the field of can...The article concluded that network pharmacology provides new ideas and insights into the molecular mechanism of traditional Chinese medicine(TCM)treatment of cancer.TCM is a new choice and hot spot in the field of cancer treatment.We have also previously published studies on TCM and network pharmacology.In this letter,we summarize the new paradigm of network pharmacology in cancer treatment mechanisms.展开更多
Erigerontis Herba(EH),the dried whole plant of Erigeron breviscapus,is well-known for circulating blood,activating meridians to alleviate pain,expelling wind,and clearing away cold.It has been extensively utilized in ...Erigerontis Herba(EH),the dried whole plant of Erigeron breviscapus,is well-known for circulating blood,activating meridians to alleviate pain,expelling wind,and clearing away cold.It has been extensively utilized in southern China for the treatment of stroke hemiplegia,chest stuffiness and pains,rheumatic arthralgia,headache,and toothache.This review focuses on the botany,ethnopharmacology,phytochemistry,pharmacology and toxicity of EH and its related prescriptions to offer new insights for prospective research of EH.Relevant information about EH was retrieved from ancient records and books,PubMed,China National Knowledge Infrastructure,Chinese Pharmacopoeia,Web of Science,Doctoral and Master’s Theses,and various electronic databases.EH is a member of Compositae family and is mainly grown in southern China.Traditional Chinese medicine records that EH has the effects of circulating blood and removing blood stasis,expelling wind,and removing cold,as well as relieving rigidity of muscle and relieving pain.By now,nearly 200 ingredients have been characterized from EH,including flavonoids,caffeoyls,aromatic acids,coumarins,pentacyclic terpenoids,volatile oil and other compounds.EH extracts,EH related prescriptions(Dengzhan Xixin injection,Dengzhan Shengmai capsules,etc.)or compounds(scutellarin,scutellarein,etc.)possessed obvious therapeutic effects of ischemic stroke,cerebral hemorrhage,myocardial infarction,Alzheimer’s disease,diabetes and its complications,gastric cancer,bone,and joint degenerative diseases.Scutellarin,the major active compound of EH,has been used as a quality marker.And no obvious toxicity of EH has been reported.According to its traditional applications,ethnopharmacology,phytochemistry,pharmacology,and toxicity,EH was applied as a valuable herb for clinical application in food and medicine fields.While several compounds have been shown to possess diverse biological activities,the underlying mechanisms of their actions remain elusive.To fully exploit the medicinal potential of EH,further studies on understanding the effective material basis and mechanisms are warranted.展开更多
Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mou...Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.展开更多
Naru Sanwei Pill,also known as Naru-3,a Mongolian medicine originating from Zhigao Pharmacopoeia,is a classic prescription used in the treatment of rheumatism.It is composed of Terminalia chebula,processed Aconitum ku...Naru Sanwei Pill,also known as Naru-3,a Mongolian medicine originating from Zhigao Pharmacopoeia,is a classic prescription used in the treatment of rheumatism.It is composed of Terminalia chebula,processed Aconitum kusnezoffii Reichb.,and Piper longum,and is known for its effects in eliminating“mucus,”relieving pain,and reducing swelling,with significant efficacy in treating joint effusion and lumbar pain.In recent years,researchers have summarized its chemical components and pharmacological effects,and employed network pharmacology methods based on the core theory of Traditional Chinese Medicine quality markers(Q-Markers)to analyze and predict its markers.The results identified potential Q-Markers for Naru-3,providing a scientific basis for quality control and further research.展开更多
Objective:To explore the mechanism of action of"Weilingxian-Guizhi"two drugs in the treatment of gout.Method:First obtain the 15 chemical components contained in the"Weilingxian-Guizhi"drug,predict...Objective:To explore the mechanism of action of"Weilingxian-Guizhi"two drugs in the treatment of gout.Method:First obtain the 15 chemical components contained in the"Weilingxian-Guizhi"drug,predict its target points through the database,and then construct the gout-related protein-protein interaction network(PPI),and then construct the"Weiling,"the"Xian,Guizhi"drug pair"active ingredient-predicted target"network,the construction of the gout-related"Weilingxian-Guizhi"drug pair"active ingredient-potential target"network,based on the Kyoto Encyclopedia of Genes and Genomes(KEGG)biological pathway enrichment analysis and gene ontology(GO)functional enrichment analysis,to study the mechanism of action of the two drugs"Weilingxian-Guizhi"in the treatment of gout.Results:The goutrelated"Weilingxian-Guizhi"drug pair"active ingredient-potential target"network contains 14 targets.KEGG pathway enrichment analysis yields 32 pathways,and GO functional enrichment analysis yields 517 GO entries.Among them,there are 468 items related to biological processes,21 items related to molecular functions,and 28 items related to cell composition.Conclusion:The results of this study initially verified and predicted the mechanism of the"Weilingxian-Cinnamon Stick"medicine on the treatment of gout,and laid a good foundation for further revealing its mechanism of action.展开更多
Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary a...Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.展开更多
The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used ...The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.展开更多
Moringa oleifera have laxative effects,but their active compositions and mechanisms are not very clear thus far.To this end,we systematically explored the active components and mechanism of M.oleifera leaves in reliev...Moringa oleifera have laxative effects,but their active compositions and mechanisms are not very clear thus far.To this end,we systematically explored the active components and mechanism of M.oleifera leaves in relieving constipation by using the slow transit constipation(STC)mouse model and network pharmacology.The results of animal experiments showed that M.oleifera aqueous extract(MOA)had good laxative activity,and its 70%alcohol soluble part(ASP)also showed significant laxative activity(P<0.01).Network pharmacological prediction results suggested that L-phenylalanine(Phe)was the key compound of ASP,and it might relieve constipation through tachykinin receptor 1(TACR1)and three kinds of adrenergic receptors,includingα_(1A)(ADRA1A),α_(2A)(ADRA2A),andα_(2B)(ADRA2B).Further animal experiment results showed that Phe significantly promoted gastrointestinal motility.Phe may relieve STC by enhancing the release of substance P(SP)and upregulating the m RNA expression of TACR1 in the ileum.Importantly,Phe may also promote intestinal movement by downregulating the m RNA expression of ADRA2A and ADRA2B and upregulating the m RNA expression of Calm and the m RNA and protein expression of myosin light chain 9 in the ileum,thereby activating the G protein-coupled receptor-myosin light chain signaling pathway.These results lay a foundation for the application of M.oleifera and Phe in constipation.展开更多
Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analys...Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analysis and network pharmacology were used to examine the pharmacological properties of Baitouweng decoction in the treatment of UC.Additionally,the potential mechanisms of action were investigated.In the meta-analysis,studies were searched from databases up to March 2024.Data from the included studies were extracted.The results were quantified by calculating the standardized mean difference(SMD).Additionally,95%confidence intervals(CI)were used to assess the precision of the estimates.Results:It was found that 201 components of Baitouweng decoction,including Pulsatillae Radix(Baitouweng),Coptidis Rhizoma(Huanglian),Phellodendri Chinensis Cortex(Huangbo),Fraxini Cortex(Qinpi),and 106 intersecting targets of UC,were obtained from INPUT.PPI and enrichment analyses showed Baitouweng decoction might regulate inflammatory response to improve UC injury.Seventeen included studies were published between 2004 and 2024.The meta-analysis results suggested that Baitouweng decoction may help increase body weight,decrease DAI and CMDI,reduce colon length shortening associated with UC,lower the spleen index,and alleviate tissue damage in colitis.In addition,Baitouweng decoction could inhibit inflammatory response and repair intestinal barrier in UC model.The protective mechanism of Baitouweng decoction was consistent with the predicted targets of network pharmacology,which suggested the results were accurate.Conclusion:Baitouweng decoction could improve UC injury by regulating the inflammatory response,cell apoptosis,and body metabolism through the integration of network pharmacology and meta-analysis.Its protective mechanisms are related to anti-inflammation,regulation of intestinal flora,brain-gut peptides,and protection of the intestinal mucosal barrier,along with modulation of body metabolism,including SCFA,bile acids,and tryptophan metabolism.展开更多
The purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn.(SNL),by LC-MS/MS,and to identify 33 compounds by positive and negative total ion flow maps.Network pharmacol...The purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn.(SNL),by LC-MS/MS,and to identify 33 compounds by positive and negative total ion flow maps.Network pharmacology and molecular docking methods were used to investigate the mechanism of action of SNL against ulcerative colitis(UC).A total of 282 component target genes and 1850 disease target genes were obtained,and 157 cross-targets and 16 core-targets were obtained after crossover.A total of 20 signaling pathways such as anti-inflammatory and anti-apoptotic were obtained by GO analysis and KEGG analysis,respectively.It is possible that the anti UC eff ect can be achieved by regulating proteins such as AKT1,EGFR,NFKB1,JUN,and HSP90AA1.Molecular docking results show that the anti UC active ingredients are well docked with the target protein molecules This study provides a scientific basis for the development and utilization of SNL.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a malignant disease with high incidence and mortality worldwide.This study focuses on the TP53 target protein to investigate the potential therapeutic effect of tetrahydrocur...BACKGROUND Hepatocellular carcinoma(HCC)is a malignant disease with high incidence and mortality worldwide.This study focuses on the TP53 target protein to investigate the potential therapeutic effect of tetrahydrocurcumin(THC)on HCC and its mechanism of action.The research hypothesis is that THC can inhibit the proliferation,migration,and invasion of HCC cells,and promote their apoptosis by regulating the TP53 target protein.AIM To explore the mechanism by which THC inhibits HCC cell proliferation via the TP53 signaling pathway.METHODS Potential targets of THC and HCC were identified from multiple databases.The core targets were subjected to analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases,and visualization processing,using the online platform Metascape to identify the key molecules and signaling pathways involved in the action of THC against HCC.The molecular mechanisms of action of THC against TP53 in the inhibition of HCC cells were verified using cell counting kit-8,Transwell,apoptosis,and western blotting assays.RESULTS Molecular docking results showed that THC had a high score for the TP53 target protein.In vitro experiments indicated that THC effectively inhibited the proliferation and migration of HCC cells,and affected the expression levels of TP53,MDM2,cyclin B,Bax,Bcl-2,caspase-9,and caspase-3.CONCLUSION THC induces the apoptosis of HCC cells through the TP53 signaling pathway,thereby inhibiting their proliferation and migration.展开更多
Objective:To screen and identify the key active molecules,signaling pathways,and therapeutic targets of Shuxuening(SXN)injection for treating liver cirrhosis(LC)and to evaluate its therapeutic potential using a mouse ...Objective:To screen and identify the key active molecules,signaling pathways,and therapeutic targets of Shuxuening(SXN)injection for treating liver cirrhosis(LC)and to evaluate its therapeutic potential using a mouse model.Methods:Target genes of SXN and LC were retrieved from public databases,and enrichment analysis was performed.A proteineprotein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),and hub genes were identified using Molecular Complex Detection(MCODE).LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride(CCl4)for 12 weeks.Starting at week 7,SXN was administered intraperitoneally to the mice in the treatment group.Serum and liver tissues of the mice were collected for the detection of indicators,pathological staining,and expression analysis of hub targets using quantitative real-time polymerase chain reaction(qRT-PCR).Results:We identified 368 overlapping genes(OLGs)between SXN and LC targets.These OLGs were subsequently used to build a PPI network and to screen for hub genes.Enrichment analysis showed that these genes were associated with cancer-related pathways,including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes,such as responses to chemicals and metabolic regulation.In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition.Furthermore,qRT-PCR demonstrated that SXN regulated the expression of MAPK8,AR and CASP3 in the livers of LC mice.Conclusion:This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods.The observed effect was associated with modulation of hub gene expression,particularly MAPK8,and CASP3.展开更多
In this editorial,we comment on the article by Micucci et al published in the recent issue.We focus on the heterogenous nature of gastric cancer(GC)and the potential benefits of integrating traditional Chinese medicin...In this editorial,we comment on the article by Micucci et al published in the recent issue.We focus on the heterogenous nature of gastric cancer(GC)and the potential benefits of integrating traditional Chinese medicine(TCM)with the modern technology of network pharmacology(NP)and omics sequencing.GC is a heterogenous disease,as it incorporates several biochemical pathways that contribute to pathogenesis.TCM acknowledges the multifactorial,heterogenous nature of disease and utilizes an integrative approach to medicine.NP,a modern philosophy within drug development,integrates traditional knowledge of nutraceuticals and modern technologies to address the complex interactions of pathways within the body.Omics technologies,which is at the core of precision medicine,has allowed for this newfound principle of drug development.Metabolic pathways are better distinguished,leading to more targeted drug development.However,the use of omics technology needs to be employed to better characterize the subtypes of GC.This will allow TCM’s use of nutraceuticals in the application of NP to better target metabolic pathways that may aid in the prevention of GC as well as enhance treatment.展开更多
KangBingDuKouFuYe(KBDKFY)is widely used to treat influenza,upper respiratory tract infections,mumps and other diseases.Due to their diverse active ingredients,it is believed that they may have excellent anti-inflammat...KangBingDuKouFuYe(KBDKFY)is widely used to treat influenza,upper respiratory tract infections,mumps and other diseases.Due to their diverse active ingredients,it is believed that they may have excellent anti-inflammatory,antibacterial and antiviral effects.Therefore,we believe they may have multiple therapeutic targets for throat inflammation caused by bacterial or viral infections.This study utilizes network pharmacology methods to analyze the therapeutic effects of KBDKFY on Bacterial Pharyngeal Tonsillitis and Viral Pharyngitis,aiming to identify its active ingredients,action targets and related pathways through molecular docking.Additionally,it determines the affinity between the main active ingredient and the core target before conducting in vitro bacteriostatic tests.The analysis results show that KBDKFY contains multiple active ingredients and potential targets for treating Bacterial Pharyngeal Tonsillitis and Viral Pharyngitis.KEGG enrichment analysis indicates that KBDKFY may have therapeutic effects on these conditions through pathways such as pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,PI3K-Akt signaling pathway,and others.This provides a theoretical basis for further exploring pharmacological effects and clinical applications of KBDKFY.展开更多
BACKGROUND Ulcerative colitis(UC),a chronic and challenging condition,necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications...BACKGROUND Ulcerative colitis(UC),a chronic and challenging condition,necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications.Traditional Chinese medicine(TCM),known for its multi-stage and multi-targeted approach,has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment.Panax ginseng(P.ginseng),a commonly used remedy for UC in TCM,exemplifies this potential,although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated,highlighting the need for further research to unlock its full potential as a treatment option.AIM To investigate the key constituents and biological pathways through which P.ginseng exerts therapeutic effects on UC.METHODS Network pharmacology investigated the UC-alleviating mechanism of P.ginseng,including“active ingredient-target-disease”network analysis,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.Panaxadiol(PD;active ingredient of P.ginseng)was tested in a mouse model of 3%dextran sulfate sodium-induced UC,with assessments of body weight,Disease Activity Index scores,and colon length.Colitis and intestinal barrier integrity were analyzed via hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining,immunohistochemistry,real time-quantitative PCR,and western blotting.RESULTS By integrating and analyzing the targets of P.ginseng and UC,15 critical hub genes were discovered.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling.Among the 10 main active ingredients identified as potentially effective,PD was most abundant and was validated in vivo to mitigate weight loss,reduce Disease Activity Index scores,and prevent colon shortening.PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators.In addition,PD increased expression of mucin and tight junction proteins.Ultimately,PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK,while increasing phosphorylation of AMPK and expression of NRF2 and NQO1.CONCLUSION PD alleviates colitis and aids intestinal barrier repair,partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways.These findings also suggest new research methods for treatment of UC with TCM.展开更多
[Objectives]To explore the mechanism of Mongolian medicine Valeriana officinalis L.on liver cancer by network pharmacology.[Methods]The HERB database of V.officinalis L.was searched,and the Uniprot database was used t...[Objectives]To explore the mechanism of Mongolian medicine Valeriana officinalis L.on liver cancer by network pharmacology.[Methods]The HERB database of V.officinalis L.was searched,and the Uniprot database was used to normalize and standardize the targets.Liver cancer targets were searched through GeneCards,DISGENET,and other databases.Venny website was used to obtain the intersection target of valerian active ingredients and liver cancer disease.The protein-protein interaction(PPI)network of the intersection targets was analyzed by STRING database,and the PPI network was constructed by Cytoscape software.The David database was used for GO functional annotation and KEGG pathway enrichment analysis to obtain the relevant pathways in the treatment of liver cancer with Mongolian medicine V.officinalis.The corresponding chemical components,targets and pathways of liver cancer were imported into Cytoscape software to construct the network topology of"chemical component-disease-target-pathway".According to the analysis results,the potential of the active components in V.officinalis as a therapeutic drug for liver cancer was evaluated,and the correlation between the results of network pharmacology analysis and clinical treatment of liver cancer was discussed,which provided a reference for clinical application.[Results]A total of 13 kinds of chemical components and 108 drug disease intersection target genes were screened,and the core genes acting on diseases were caffeic acid,perillyl acetate,(+)-alpha-Terpineol,eucalyptol,etc.;GO functional enrichment analysis involved 389 items of biological processes,62 items of cellular components and 120 items of molecular functions.Enrichment analysis of KEGG signaling pathways screened out chemical carcinogenesis-receptor activation,cancer pathways,prolactin signaling pathways,proteoglycans in cancer,EGFR tyrosine kinase inhibitor resistance and other signaling pathways.[Conclusions]The mechanism of Mongolian medicine V.officinalis on liver cancer was studied by network pharmacology.It was found that it can inhibit the proliferation of liver cancer cells from multiple targets and pathways.This is expected to provide a theoretical basis for further basic experimental research.展开更多
[Objectives]To investigate the efficacy and mechanisms of action of the Dangshen Xiangfu Chinese herbal patch through the application of network pharmacology.[Methods]The HIT 2.0 database and the TCMSP database were u...[Objectives]To investigate the efficacy and mechanisms of action of the Dangshen Xiangfu Chinese herbal patch through the application of network pharmacology.[Methods]The HIT 2.0 database and the TCMSP database were utilized to identify and gather the active ingredients and corresponding action targets of the Dangshen Xiangfu Chinese herbal patch.Cytoscape software was utilized to create network diagrams and analyze the primary active ingredients and action targets of the herbal patch formulation.Gene Ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the identified action targets were conducted using the DAVID database.The SymMap database was utilized to analyze the network information pertaining to traditional Chinese medicine(TCM),syndromes and the associated symptoms of the medicinal plants found in the Chinese herbal patch.[Results]The network pharmacological analysis suggested that the primary Chinese herbal ingredients of the Dangshen Xiangfu Chinese herbal patch may include Radix Glycyrrhizae Preparata,Fructus Aurantii,Cyperi Rhizoma,Radix Codonopsis,etc.The primary active ingredients may include quercetin,luteolin,kaempferol,fisetin,nobiletin,naringenin,isosinensetin,baicalin,etc.These ingredients exhibited a protective effect on the intestinal tract and were advantageous in the regulation of abnormal intestinal function.The primary targets of action included PTGS2,CASP3,HSP90AA1,PTGS1,AKT1,and MMP9.The active ingredients of the Dangshen Xiangfu Chinese herbal patch may exert a regulatory effect on gastrointestinal inflammation by interacting with the pertinent targets within the PI3K-Akt signaling pathway,the IL-17 signaling pathway,and other related pathways in the body.The principal symptoms associated with this condition may include qi stagnation,qi deficiency,and food accumulation.[Conclusions]This study offers a framework for analyzing the efficacy and mechanisms of action of external preparations derived from medicinal plants.展开更多
OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential ...OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential mechanism of TFK against T2DM.Initially,we filtered bioactive compounds with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Symptom Mapping(Sym Map),and gathered targets of TFK and T2DM.Subsequently,we constructed a protein-protein interaction(PPI)network,enriched core targets through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and adopted molecular docking to study the binding mode of compounds and the signaling pathway.Finally,we employed a KKAy mice model to investigate the effect and mechanism of TFK against T2DM.Biochemical assay,histology assay,and Western blot(WB)were used to assess the mechanism.RESULTS:There were 492 bioactive compounds of TFK screened,and 1226 overlapping targets of TFK against T2DM identified.A compound-T2DM-related target network with 997 nodes and 4439 edges was constructed.KEGG enrichment analysis identified some core pathways related to T2DM,including adenosine 5-monophosphate-activated protein kinase(AMPK)signaling pathway.Molecular docking study revealed that compounds of TFK,including citric acid,could bind to the active pocket of AMPK crystal structure with free binding energy of-4.8,-8 and-7.9,respectively.Animal experiments indicated that TFK decreased body weight,fasting blood glucose,fasting serum insulin,homeostasis model of insulin resistance,glycosylated serum protein,total cholesterol,triglyceride,and low-density lipoprotein cholesterol,and improve oral glucose tolerance test results.TFK reduced steatosis in liver tissue,and infiltration of inflammatory cells,and protected liver cells to a certain extent.WB analysis revealed that,TFK upregulated the phosphorylation of AMPK and branchedchainα-ketoacid dehydrogenase proteins.CONCLUSION:TFK has the potential to effectively manage T2DM,possibly by regulating the AMPK signaling pathway.The present study lays a new foundation for the therapeutic application of TFK in the treatment of T2DM.展开更多
Objective:To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata(Willd.)Ohwi root(P.lobata,Ge Gen)and Hovenia dulcis Thunb.(H.dulcis,Zhi Ju Zi)against ethanol-induced live...Objective:To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata(Willd.)Ohwi root(P.lobata,Ge Gen)and Hovenia dulcis Thunb.(H.dulcis,Zhi Ju Zi)against ethanol-induced liver damage in vitro,using a human hepatoma cell line G2(HepG2)cell model.Methods:HepG2 cells were cultured in medium containing 4%ethanol to establish a model of alcoholic liver damage.The cells were then treated with the combined extract obtained via cryogenic extraction.Biochemical assays and Western blot analyses were performed to assess the levels of oxidative stress markers,antioxidant enzymes,and inflammatory cytokines.In addition,activation of the phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)pathway was examined to elucidate the mechanisms underlying the effects of the extract.Results:Treatment with the extract contributed to a significant reduction in the release of nitric oxide and reactive oxygen species in the ethanol-treated HepG2 cells;promoted the elevated expression of superoxide dismutase,catalase,and glutathione,indicating enhanced antioxidant defenses;and showed strong free radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radicals.In addition,by activating the PI3K/AKT pathway,treatment promoted increases in the expression of nuclear factor erythroid 2-related factor 2 and its downstream targets,subsequently inhibiting apoptosis.Moreover.inflammatory responses were mitigated,as indicated by reductions in the expression of tumor necrosis factor-alpha and interleukin-6,and we detected reduction in the levels of alanine aminotransferase and aspartate aminotransferase,thereby indicating hepatoprotective effects.Conclusion:The combined P.lobata root and H.dulcis extract was established to have notable antioxidative and anti-inflammatory properties,effectively alleviating ethanol-induced liver damage in vitro.These findings highlight the potential applicability of this extract as a candidate for treating alcoholic liver disease.展开更多
BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine t...BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.展开更多
文摘The article concluded that network pharmacology provides new ideas and insights into the molecular mechanism of traditional Chinese medicine(TCM)treatment of cancer.TCM is a new choice and hot spot in the field of cancer treatment.We have also previously published studies on TCM and network pharmacology.In this letter,we summarize the new paradigm of network pharmacology in cancer treatment mechanisms.
基金funded by the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources(Guangxi Normal University)(CMEMR2022-B11)the Natural Science Research of Jiangsu Higher education Institution of China(22KJB360018)Jiangsu Province University Student Innovation and Entrepreneurial Training Program(202311117019Z).
文摘Erigerontis Herba(EH),the dried whole plant of Erigeron breviscapus,is well-known for circulating blood,activating meridians to alleviate pain,expelling wind,and clearing away cold.It has been extensively utilized in southern China for the treatment of stroke hemiplegia,chest stuffiness and pains,rheumatic arthralgia,headache,and toothache.This review focuses on the botany,ethnopharmacology,phytochemistry,pharmacology and toxicity of EH and its related prescriptions to offer new insights for prospective research of EH.Relevant information about EH was retrieved from ancient records and books,PubMed,China National Knowledge Infrastructure,Chinese Pharmacopoeia,Web of Science,Doctoral and Master’s Theses,and various electronic databases.EH is a member of Compositae family and is mainly grown in southern China.Traditional Chinese medicine records that EH has the effects of circulating blood and removing blood stasis,expelling wind,and removing cold,as well as relieving rigidity of muscle and relieving pain.By now,nearly 200 ingredients have been characterized from EH,including flavonoids,caffeoyls,aromatic acids,coumarins,pentacyclic terpenoids,volatile oil and other compounds.EH extracts,EH related prescriptions(Dengzhan Xixin injection,Dengzhan Shengmai capsules,etc.)or compounds(scutellarin,scutellarein,etc.)possessed obvious therapeutic effects of ischemic stroke,cerebral hemorrhage,myocardial infarction,Alzheimer’s disease,diabetes and its complications,gastric cancer,bone,and joint degenerative diseases.Scutellarin,the major active compound of EH,has been used as a quality marker.And no obvious toxicity of EH has been reported.According to its traditional applications,ethnopharmacology,phytochemistry,pharmacology,and toxicity,EH was applied as a valuable herb for clinical application in food and medicine fields.While several compounds have been shown to possess diverse biological activities,the underlying mechanisms of their actions remain elusive.To fully exploit the medicinal potential of EH,further studies on understanding the effective material basis and mechanisms are warranted.
基金Science Foundation of Hunan Province(2021JJ40510)General Guidance Project of Hunan Health Commission(202203074169)+1 种基金Clinical Medical Technology Innovation Guidance Project of Hunan Province(2021SK51901)and Key Guiding Projects of Hunan Health Commission(20201918)for supporting this study.
文摘Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.
文摘Naru Sanwei Pill,also known as Naru-3,a Mongolian medicine originating from Zhigao Pharmacopoeia,is a classic prescription used in the treatment of rheumatism.It is composed of Terminalia chebula,processed Aconitum kusnezoffii Reichb.,and Piper longum,and is known for its effects in eliminating“mucus,”relieving pain,and reducing swelling,with significant efficacy in treating joint effusion and lumbar pain.In recent years,researchers have summarized its chemical components and pharmacological effects,and employed network pharmacology methods based on the core theory of Traditional Chinese Medicine quality markers(Q-Markers)to analyze and predict its markers.The results identified potential Q-Markers for Naru-3,providing a scientific basis for quality control and further research.
文摘Objective:To explore the mechanism of action of"Weilingxian-Guizhi"two drugs in the treatment of gout.Method:First obtain the 15 chemical components contained in the"Weilingxian-Guizhi"drug,predict its target points through the database,and then construct the gout-related protein-protein interaction network(PPI),and then construct the"Weiling,"the"Xian,Guizhi"drug pair"active ingredient-predicted target"network,the construction of the gout-related"Weilingxian-Guizhi"drug pair"active ingredient-potential target"network,based on the Kyoto Encyclopedia of Genes and Genomes(KEGG)biological pathway enrichment analysis and gene ontology(GO)functional enrichment analysis,to study the mechanism of action of the two drugs"Weilingxian-Guizhi"in the treatment of gout.Results:The goutrelated"Weilingxian-Guizhi"drug pair"active ingredient-potential target"network contains 14 targets.KEGG pathway enrichment analysis yields 32 pathways,and GO functional enrichment analysis yields 517 GO entries.Among them,there are 468 items related to biological processes,21 items related to molecular functions,and 28 items related to cell composition.Conclusion:The results of this study initially verified and predicted the mechanism of the"Weilingxian-Cinnamon Stick"medicine on the treatment of gout,and laid a good foundation for further revealing its mechanism of action.
基金supported by the National Natural Science Foundation of China(Grant No.82270892)Natural Science Foundation of Hubei Province(Grant No.2022CFB287)+2 种基金Xianning City Science and Technology Plan Project(Grant No.2022ZRKX052)School projects of Hubei University of Science and Technology(Grant No.2022T01,2021WG05,2021TNB01)Hubei University of Science and Technology School-level Fund(Grant No.BK202122).
文摘Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.
基金supported by 2024 Liaoning Province Graduate Education Teaching Reform Research Project(LNYJG2024251).
文摘The aim of this study was to explore the mechanism of action of sea buckthorn polyphenols in the treatment of hyperlipidemia through network pharmacology and molecular docking.The TCMSP pharmacology database was used to screen the polyphenols present in sea buckthorn,and then the SwissTargetPrediction and Uniprot databases were used to obtain the potential targets of sea buckthorn polyphenols,which were supplemented by the literature.In total,7 polyphenols and 154 potential targets were obtained.Through GeneCards,OMIM database,1358 hyperlipidemia-related targets were collected.We found that there were 101 targets at the intersection of components and diseases.Through GO and KEGG enrichment analysis,27 core targets were obtained,which were AKT1,TNF,TP53,IL-6,etc.in order of degree value.174 pathways were obtained from KEGG enrichment analysis,including AGE-RAGE signaling pathway in diabetic complications,fl uid shear stress and atherosclerosis,lipid and atherosclerosis,etc.The molecular docking of the main components to the targets was performed using OpenBabelGUI,AutoDockTools-1.5.6 software.Finally,the results were visualized using Cytoscape 3.9.1 software.The molecular docking results showed that sea buckthorn polyphenols have good binding ability with the key targets.Among them,such as quercetin and kaempferol,have good binding ability with TNF,TP53 and IL-6.For example,TNF binds to quercetin with a binding energy of-5.34 kcal/mol and to kaempferol with a binding energy of-6.22 kcal/mol;TP53 binds to kaempferol with a binding energy of-5.32 kcal/mol;IL-6 binds to quercetin with a binding energy of-5.62 kcal/mol,etc.Therefore,the network pharmacology study showed that the treatment of hyperlipidemia by sea buckthorn polyphenols can be realized by multi-component-multi-target-multi-pathway together,which provides some reference for the later study of sea buckthorn polyphenols in the treatment of hyperlipidemia.
文摘Moringa oleifera have laxative effects,but their active compositions and mechanisms are not very clear thus far.To this end,we systematically explored the active components and mechanism of M.oleifera leaves in relieving constipation by using the slow transit constipation(STC)mouse model and network pharmacology.The results of animal experiments showed that M.oleifera aqueous extract(MOA)had good laxative activity,and its 70%alcohol soluble part(ASP)also showed significant laxative activity(P<0.01).Network pharmacological prediction results suggested that L-phenylalanine(Phe)was the key compound of ASP,and it might relieve constipation through tachykinin receptor 1(TACR1)and three kinds of adrenergic receptors,includingα_(1A)(ADRA1A),α_(2A)(ADRA2A),andα_(2B)(ADRA2B).Further animal experiment results showed that Phe significantly promoted gastrointestinal motility.Phe may relieve STC by enhancing the release of substance P(SP)and upregulating the m RNA expression of TACR1 in the ileum.Importantly,Phe may also promote intestinal movement by downregulating the m RNA expression of ADRA2A and ADRA2B and upregulating the m RNA expression of Calm and the m RNA and protein expression of myosin light chain 9 in the ileum,thereby activating the G protein-coupled receptor-myosin light chain signaling pathway.These results lay a foundation for the application of M.oleifera and Phe in constipation.
基金supported by the National Natural Science Foundation of China(No.82405237,82373835,82173781)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515110768,2019A1515010806)+3 种基金Foshan Science and Technology Bureau’s self funded project(No.2320001007283)Key Field Projects(Intelligent Manufacturing)of General Universities in Guangdong Province(No.2020ZDZX2057)the Scientific Research Projects(Characteristic Innovation)of General Universities in Guangdong Province(No.2019KTSCX195)Guangdong Provincial Medical Research Foundation(No.A2022061).
文摘Background:Baitouweng decoction is a classic prescription for treating chronic dysentery and mainly used to treat heat-toxic dysentery and is widely used in damp-heat ulcerative colitis(UC)in China.Methods:Meta-analysis and network pharmacology were used to examine the pharmacological properties of Baitouweng decoction in the treatment of UC.Additionally,the potential mechanisms of action were investigated.In the meta-analysis,studies were searched from databases up to March 2024.Data from the included studies were extracted.The results were quantified by calculating the standardized mean difference(SMD).Additionally,95%confidence intervals(CI)were used to assess the precision of the estimates.Results:It was found that 201 components of Baitouweng decoction,including Pulsatillae Radix(Baitouweng),Coptidis Rhizoma(Huanglian),Phellodendri Chinensis Cortex(Huangbo),Fraxini Cortex(Qinpi),and 106 intersecting targets of UC,were obtained from INPUT.PPI and enrichment analyses showed Baitouweng decoction might regulate inflammatory response to improve UC injury.Seventeen included studies were published between 2004 and 2024.The meta-analysis results suggested that Baitouweng decoction may help increase body weight,decrease DAI and CMDI,reduce colon length shortening associated with UC,lower the spleen index,and alleviate tissue damage in colitis.In addition,Baitouweng decoction could inhibit inflammatory response and repair intestinal barrier in UC model.The protective mechanism of Baitouweng decoction was consistent with the predicted targets of network pharmacology,which suggested the results were accurate.Conclusion:Baitouweng decoction could improve UC injury by regulating the inflammatory response,cell apoptosis,and body metabolism through the integration of network pharmacology and meta-analysis.Its protective mechanisms are related to anti-inflammation,regulation of intestinal flora,brain-gut peptides,and protection of the intestinal mucosal barrier,along with modulation of body metabolism,including SCFA,bile acids,and tryptophan metabolism.
文摘The purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn.(SNL),by LC-MS/MS,and to identify 33 compounds by positive and negative total ion flow maps.Network pharmacology and molecular docking methods were used to investigate the mechanism of action of SNL against ulcerative colitis(UC).A total of 282 component target genes and 1850 disease target genes were obtained,and 157 cross-targets and 16 core-targets were obtained after crossover.A total of 20 signaling pathways such as anti-inflammatory and anti-apoptotic were obtained by GO analysis and KEGG analysis,respectively.It is possible that the anti UC eff ect can be achieved by regulating proteins such as AKT1,EGFR,NFKB1,JUN,and HSP90AA1.Molecular docking results show that the anti UC active ingredients are well docked with the target protein molecules This study provides a scientific basis for the development and utilization of SNL.
基金The Central Government Guides Local Science and Technology Development Fund,No.2023JH6/100100021Liaoning Province Education Department Foundation of China,No.JYTMS20231393 and No.LJ212410164032+2 种基金Scientific Research Project of the Liaoning Province Education Department,No.SYYX2019015Science and Technology Foundation of Shenyang Medical College,No.20171004the Science and Technology Innovation Fund for Master Students of Shenyang Medical College,No.Y20220509.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a malignant disease with high incidence and mortality worldwide.This study focuses on the TP53 target protein to investigate the potential therapeutic effect of tetrahydrocurcumin(THC)on HCC and its mechanism of action.The research hypothesis is that THC can inhibit the proliferation,migration,and invasion of HCC cells,and promote their apoptosis by regulating the TP53 target protein.AIM To explore the mechanism by which THC inhibits HCC cell proliferation via the TP53 signaling pathway.METHODS Potential targets of THC and HCC were identified from multiple databases.The core targets were subjected to analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases,and visualization processing,using the online platform Metascape to identify the key molecules and signaling pathways involved in the action of THC against HCC.The molecular mechanisms of action of THC against TP53 in the inhibition of HCC cells were verified using cell counting kit-8,Transwell,apoptosis,and western blotting assays.RESULTS Molecular docking results showed that THC had a high score for the TP53 target protein.In vitro experiments indicated that THC effectively inhibited the proliferation and migration of HCC cells,and affected the expression levels of TP53,MDM2,cyclin B,Bax,Bcl-2,caspase-9,and caspase-3.CONCLUSION THC induces the apoptosis of HCC cells through the TP53 signaling pathway,thereby inhibiting their proliferation and migration.
基金Our study was funded by the Clinical Research Special Fund of Wu Jieping Medical Foundation(320.6750.2022-25-8)the Fundamental Research Funds for the Cornell University(2024-JYBXJSJJ042 and 2024-JYB-JBZD-058).
文摘Objective:To screen and identify the key active molecules,signaling pathways,and therapeutic targets of Shuxuening(SXN)injection for treating liver cirrhosis(LC)and to evaluate its therapeutic potential using a mouse model.Methods:Target genes of SXN and LC were retrieved from public databases,and enrichment analysis was performed.A proteineprotein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),and hub genes were identified using Molecular Complex Detection(MCODE).LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride(CCl4)for 12 weeks.Starting at week 7,SXN was administered intraperitoneally to the mice in the treatment group.Serum and liver tissues of the mice were collected for the detection of indicators,pathological staining,and expression analysis of hub targets using quantitative real-time polymerase chain reaction(qRT-PCR).Results:We identified 368 overlapping genes(OLGs)between SXN and LC targets.These OLGs were subsequently used to build a PPI network and to screen for hub genes.Enrichment analysis showed that these genes were associated with cancer-related pathways,including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes,such as responses to chemicals and metabolic regulation.In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition.Furthermore,qRT-PCR demonstrated that SXN regulated the expression of MAPK8,AR and CASP3 in the livers of LC mice.Conclusion:This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods.The observed effect was associated with modulation of hub gene expression,particularly MAPK8,and CASP3.
文摘In this editorial,we comment on the article by Micucci et al published in the recent issue.We focus on the heterogenous nature of gastric cancer(GC)and the potential benefits of integrating traditional Chinese medicine(TCM)with the modern technology of network pharmacology(NP)and omics sequencing.GC is a heterogenous disease,as it incorporates several biochemical pathways that contribute to pathogenesis.TCM acknowledges the multifactorial,heterogenous nature of disease and utilizes an integrative approach to medicine.NP,a modern philosophy within drug development,integrates traditional knowledge of nutraceuticals and modern technologies to address the complex interactions of pathways within the body.Omics technologies,which is at the core of precision medicine,has allowed for this newfound principle of drug development.Metabolic pathways are better distinguished,leading to more targeted drug development.However,the use of omics technology needs to be employed to better characterize the subtypes of GC.This will allow TCM’s use of nutraceuticals in the application of NP to better target metabolic pathways that may aid in the prevention of GC as well as enhance treatment.
基金supported by Scientific Research Fund Project of Education Department of Liaoning Province(LJKZ0960)Science Foundation of Shenyang Pharmaceutical University(GGJJ2021105)National College Student Innovation and Entrepreneurship Project.
文摘KangBingDuKouFuYe(KBDKFY)is widely used to treat influenza,upper respiratory tract infections,mumps and other diseases.Due to their diverse active ingredients,it is believed that they may have excellent anti-inflammatory,antibacterial and antiviral effects.Therefore,we believe they may have multiple therapeutic targets for throat inflammation caused by bacterial or viral infections.This study utilizes network pharmacology methods to analyze the therapeutic effects of KBDKFY on Bacterial Pharyngeal Tonsillitis and Viral Pharyngitis,aiming to identify its active ingredients,action targets and related pathways through molecular docking.Additionally,it determines the affinity between the main active ingredient and the core target before conducting in vitro bacteriostatic tests.The analysis results show that KBDKFY contains multiple active ingredients and potential targets for treating Bacterial Pharyngeal Tonsillitis and Viral Pharyngitis.KEGG enrichment analysis indicates that KBDKFY may have therapeutic effects on these conditions through pathways such as pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,PI3K-Akt signaling pathway,and others.This provides a theoretical basis for further exploring pharmacological effects and clinical applications of KBDKFY.
基金Supported by Provincial Key Cultivation Laboratory for Digestive Disease Research,Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021SYS13,No.2020SYS13 and No.2021MX03.
文摘BACKGROUND Ulcerative colitis(UC),a chronic and challenging condition,necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications.Traditional Chinese medicine(TCM),known for its multi-stage and multi-targeted approach,has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment.Panax ginseng(P.ginseng),a commonly used remedy for UC in TCM,exemplifies this potential,although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated,highlighting the need for further research to unlock its full potential as a treatment option.AIM To investigate the key constituents and biological pathways through which P.ginseng exerts therapeutic effects on UC.METHODS Network pharmacology investigated the UC-alleviating mechanism of P.ginseng,including“active ingredient-target-disease”network analysis,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.Panaxadiol(PD;active ingredient of P.ginseng)was tested in a mouse model of 3%dextran sulfate sodium-induced UC,with assessments of body weight,Disease Activity Index scores,and colon length.Colitis and intestinal barrier integrity were analyzed via hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining,immunohistochemistry,real time-quantitative PCR,and western blotting.RESULTS By integrating and analyzing the targets of P.ginseng and UC,15 critical hub genes were discovered.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling.Among the 10 main active ingredients identified as potentially effective,PD was most abundant and was validated in vivo to mitigate weight loss,reduce Disease Activity Index scores,and prevent colon shortening.PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators.In addition,PD increased expression of mucin and tight junction proteins.Ultimately,PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK,while increasing phosphorylation of AMPK and expression of NRF2 and NQO1.CONCLUSION PD alleviates colitis and aids intestinal barrier repair,partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways.These findings also suggest new research methods for treatment of UC with TCM.
基金Supported by National Natural Science Foundation of China(82260844)Natural Science Foundation of Inner Mongolia(2022LHMS08021).
文摘[Objectives]To explore the mechanism of Mongolian medicine Valeriana officinalis L.on liver cancer by network pharmacology.[Methods]The HERB database of V.officinalis L.was searched,and the Uniprot database was used to normalize and standardize the targets.Liver cancer targets were searched through GeneCards,DISGENET,and other databases.Venny website was used to obtain the intersection target of valerian active ingredients and liver cancer disease.The protein-protein interaction(PPI)network of the intersection targets was analyzed by STRING database,and the PPI network was constructed by Cytoscape software.The David database was used for GO functional annotation and KEGG pathway enrichment analysis to obtain the relevant pathways in the treatment of liver cancer with Mongolian medicine V.officinalis.The corresponding chemical components,targets and pathways of liver cancer were imported into Cytoscape software to construct the network topology of"chemical component-disease-target-pathway".According to the analysis results,the potential of the active components in V.officinalis as a therapeutic drug for liver cancer was evaluated,and the correlation between the results of network pharmacology analysis and clinical treatment of liver cancer was discussed,which provided a reference for clinical application.[Results]A total of 13 kinds of chemical components and 108 drug disease intersection target genes were screened,and the core genes acting on diseases were caffeic acid,perillyl acetate,(+)-alpha-Terpineol,eucalyptol,etc.;GO functional enrichment analysis involved 389 items of biological processes,62 items of cellular components and 120 items of molecular functions.Enrichment analysis of KEGG signaling pathways screened out chemical carcinogenesis-receptor activation,cancer pathways,prolactin signaling pathways,proteoglycans in cancer,EGFR tyrosine kinase inhibitor resistance and other signaling pathways.[Conclusions]The mechanism of Mongolian medicine V.officinalis on liver cancer was studied by network pharmacology.It was found that it can inhibit the proliferation of liver cancer cells from multiple targets and pathways.This is expected to provide a theoretical basis for further basic experimental research.
基金Supported by Shanghai Putuo District Science and Technology R&D Platform Project(2024QX04).
文摘[Objectives]To investigate the efficacy and mechanisms of action of the Dangshen Xiangfu Chinese herbal patch through the application of network pharmacology.[Methods]The HIT 2.0 database and the TCMSP database were utilized to identify and gather the active ingredients and corresponding action targets of the Dangshen Xiangfu Chinese herbal patch.Cytoscape software was utilized to create network diagrams and analyze the primary active ingredients and action targets of the herbal patch formulation.Gene Ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the identified action targets were conducted using the DAVID database.The SymMap database was utilized to analyze the network information pertaining to traditional Chinese medicine(TCM),syndromes and the associated symptoms of the medicinal plants found in the Chinese herbal patch.[Results]The network pharmacological analysis suggested that the primary Chinese herbal ingredients of the Dangshen Xiangfu Chinese herbal patch may include Radix Glycyrrhizae Preparata,Fructus Aurantii,Cyperi Rhizoma,Radix Codonopsis,etc.The primary active ingredients may include quercetin,luteolin,kaempferol,fisetin,nobiletin,naringenin,isosinensetin,baicalin,etc.These ingredients exhibited a protective effect on the intestinal tract and were advantageous in the regulation of abnormal intestinal function.The primary targets of action included PTGS2,CASP3,HSP90AA1,PTGS1,AKT1,and MMP9.The active ingredients of the Dangshen Xiangfu Chinese herbal patch may exert a regulatory effect on gastrointestinal inflammation by interacting with the pertinent targets within the PI3K-Akt signaling pathway,the IL-17 signaling pathway,and other related pathways in the body.The principal symptoms associated with this condition may include qi stagnation,qi deficiency,and food accumulation.[Conclusions]This study offers a framework for analyzing the efficacy and mechanisms of action of external preparations derived from medicinal plants.
基金Tsinghua Precision Medicine Foundation:Tangfukang Plays the Therapeutic Role in Type 2 Diabetes Patients with Qi and Yin Deficiency Syndrome by Regulating the Intestinal Flora Mediated Branched-chain Amino Acids-Phosphatidylinositide 3-Kinases-Protein Kinase B Signaling Pathway(grant number 10001020105)National Natural Science Foundation of China:Tangfukang Plays the Therapeutic Role in Type 2 Diabetes Mellitus by Regulating the Intestinal Flora Mediated Adiponectin-adenosine 5-Monophosphate-activated Protein Kinase-branched-chain Amino Acids Signaling Pathway(grant number 82104812)。
文摘OBJECTIVE:To explore the mechanism of Tangfukang formula(糖复康方,TFK)in treating type 2 diabetes mellitus(T2DM).METHODS:We employed network pharmacology combined with experimental validation to explore the potential mechanism of TFK against T2DM.Initially,we filtered bioactive compounds with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Symptom Mapping(Sym Map),and gathered targets of TFK and T2DM.Subsequently,we constructed a protein-protein interaction(PPI)network,enriched core targets through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and adopted molecular docking to study the binding mode of compounds and the signaling pathway.Finally,we employed a KKAy mice model to investigate the effect and mechanism of TFK against T2DM.Biochemical assay,histology assay,and Western blot(WB)were used to assess the mechanism.RESULTS:There were 492 bioactive compounds of TFK screened,and 1226 overlapping targets of TFK against T2DM identified.A compound-T2DM-related target network with 997 nodes and 4439 edges was constructed.KEGG enrichment analysis identified some core pathways related to T2DM,including adenosine 5-monophosphate-activated protein kinase(AMPK)signaling pathway.Molecular docking study revealed that compounds of TFK,including citric acid,could bind to the active pocket of AMPK crystal structure with free binding energy of-4.8,-8 and-7.9,respectively.Animal experiments indicated that TFK decreased body weight,fasting blood glucose,fasting serum insulin,homeostasis model of insulin resistance,glycosylated serum protein,total cholesterol,triglyceride,and low-density lipoprotein cholesterol,and improve oral glucose tolerance test results.TFK reduced steatosis in liver tissue,and infiltration of inflammatory cells,and protected liver cells to a certain extent.WB analysis revealed that,TFK upregulated the phosphorylation of AMPK and branchedchainα-ketoacid dehydrogenase proteins.CONCLUSION:TFK has the potential to effectively manage T2DM,possibly by regulating the AMPK signaling pathway.The present study lays a new foundation for the therapeutic application of TFK in the treatment of T2DM.
基金supported by the National Natural Science Foundation of China(82004027)the Fundamental Research Funds for the Central Universities(JUSRP11961).
文摘Objective:To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata(Willd.)Ohwi root(P.lobata,Ge Gen)and Hovenia dulcis Thunb.(H.dulcis,Zhi Ju Zi)against ethanol-induced liver damage in vitro,using a human hepatoma cell line G2(HepG2)cell model.Methods:HepG2 cells were cultured in medium containing 4%ethanol to establish a model of alcoholic liver damage.The cells were then treated with the combined extract obtained via cryogenic extraction.Biochemical assays and Western blot analyses were performed to assess the levels of oxidative stress markers,antioxidant enzymes,and inflammatory cytokines.In addition,activation of the phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)pathway was examined to elucidate the mechanisms underlying the effects of the extract.Results:Treatment with the extract contributed to a significant reduction in the release of nitric oxide and reactive oxygen species in the ethanol-treated HepG2 cells;promoted the elevated expression of superoxide dismutase,catalase,and glutathione,indicating enhanced antioxidant defenses;and showed strong free radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radicals.In addition,by activating the PI3K/AKT pathway,treatment promoted increases in the expression of nuclear factor erythroid 2-related factor 2 and its downstream targets,subsequently inhibiting apoptosis.Moreover.inflammatory responses were mitigated,as indicated by reductions in the expression of tumor necrosis factor-alpha and interleukin-6,and we detected reduction in the levels of alanine aminotransferase and aspartate aminotransferase,thereby indicating hepatoprotective effects.Conclusion:The combined P.lobata root and H.dulcis extract was established to have notable antioxidative and anti-inflammatory properties,effectively alleviating ethanol-induced liver damage in vitro.These findings highlight the potential applicability of this extract as a candidate for treating alcoholic liver disease.
基金West Light Foundation of the Ningxia Key Research and Development Program,No.2023BEG02015High-level Key Discipline Construction Project of State Administration of Traditional Chinese Medicine,No.2022-226+1 种基金Talent Development Projects of Young Qihuang of National Administration of Traditional Chinese Medicine,No.2020-218National Natural Science Foundation of China,No.82374261.
文摘BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.
