1.Discipline origins In 1984,“analytical pharmacology”was firstly used in the paper entitled“The future of analytical pharmacologyda personal view”by Dr.J.S.Cridland,director of a clinical pharmacological laborato...1.Discipline origins In 1984,“analytical pharmacology”was firstly used in the paper entitled“The future of analytical pharmacologyda personal view”by Dr.J.S.Cridland,director of a clinical pharmacological laboratory at Department of Pharmacology,University of Cape Town.He proposed“Analytical pharmacology is at present usually a tool of clinical pharmacology”,which is mainly used for therapeutic drug monitoring,analysis of clinical pharmacokinetics,and toxicological screening to provide a basis for reasonable medication and clinical dose adjustment[1].In 1984,W.J.Black,Director of Wellcome Research Laboratories,was offered a personal Chair at King's College Hospital School of Medicine and Dentistry,part of King's College London.He chose“Analytical Pharmacology”as a title for the Chair[2].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 Meat originating from the spent hen is an important source of poultry meat production;however,multiple factors cause the decline in the meat quality of spent hens.Chinese herbs have been widely used as medi...Background Meat originating from the spent hen is an important source of poultry meat production;however,multiple factors cause the decline in the meat quality of spent hens.Chinese herbs have been widely used as medi-cine for a long time to prevent diseases and as nutrient supplements to improve the product quality.This experi-ment explored the effects of adding 1.0%Chinese herbal formula(CHF,including 0.30%Leonurus japonicus Houtt.,0.20%Salvia miltiorrhiza Bge.,0.25%Ligustrum lucidum Ait.,and 0.25%Taraxacum mongolicum Hand.-Mazz.)for 120 d to the spent hens’diet through metabolomics,network pharmacology,and microbiome strategies.Results The results indicated that CHF supplementation improved the meat quality by reducing drip loss(P<0.05),b*value(P=0.058),and shear force(P=0.099)and increasing cooked meat percentage(P=0.054)and dry matter(P<0.05)of breast muscle.The addition of CHF improved the nutritional value of breast muscle by increasing(P<0.05)the content of C18:2n-6,n-6/n-3 polyunsaturated fatty acids(PUFA),total PUFA,PUFA-to-saturated fatty acids(SFA)ratio,and hypocholesterolemic-to-hypercholesterolemic ratio,and tending to increase serine content(P=0.069).The targeted metabolomics analysis revealed that the biosynthesis of SFA,linoleic acid metabolism,fatty acid degradation,fatty acid elongation,and fatty acid biosynthesis pathways were enriched by CHF supplementation.Furthermore,the network pharmacology analysis indicated that CHF was closely associated with oxidative stress and lipid metabo-lism.The CHF supplementation increased the glutathione peroxidase level(P<0.05)and upregulated gene expres-sion related to the Nrf2 pathway(including HO-1,P<0.05;Nrf2,P=0.098;CAT,P=0.060;GPX1,P=0.063;and SOD2,P=0.052)and lipid metabolism(including PPARγ,P<0.05;SREBP1,P=0.059;and CPT1A,P=0.058).Additionally,CHF supplementation increased Firmicutes and decreased Bacteroidetes,Spirochaetes,and Synergistetes abundances(P<0.05),which may contribute to better meat quality.Conclusions Our results suggest that CHF supplementation improved the quality and nutritional value of meat,which will provide a theoretical basis for the utilization of CHF as a feed additive in spent hens’diets.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
The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three ...The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three Combinations”).However,considering TCM's distinctive features of“syndrome differentiation and treatment”and“multicomponent formulations and complex mechanisms”,current TCM drug development faces challenges such as insufficient understanding of the material basis and the overall mechanism of action and an incomplete evidence chain system.Moreover,significant obstacles persist in gathering human experience data,evaluating clinical efficacy,and controlling the quality of active ingredients,which impede the innovation process in TCM drug development.Network pharmacology,centered on the“network targets”theory,transcends the limitations of the conventional“single target”reductionist research model.It emphasizes the comprehensive effects of disease or syndrome biological networks as targets to elucidate the overall regulatory mechanism of TCM prescriptions.This approach aligns with the holistic perspective of TCM,offering a novel method consistent with TCM's holistic view for investigating the complex mechanisms of TCM and developing new TCM drugs.It is internationally recognized as a“next-generation drug research model”.To advance the research of new tools,methods,and standards for TCM evaluation and to overcome fundamental,critical,and cutting-edge technical challenges in TCM regulation,this consensus aims to explore the characteristics,progress,challenges,applicable pathways,and specific applications of network pharmacology as a new theory,method,and tool in TCM drug development.The goal is to enhance the quality of TCM drug research and development and accelerate the efficiency of developing new TCM products.展开更多
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
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
The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,...The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,and the network pharmacology was used to elucidate their anti-hair loss mechanism,which was verified by molecular docking technology.572 active compounds were identified from the ASE by metabolomics methods,where there are 1447 corresponding targets and 492 targets related to hair loss,totaling 88 targets.20 core active substances were identified by constructing a network between common targets and active substances,which include vanillic acid,chorionic acid,caffeic acid and apigenin.The five key targets of TNF,TP53,IL6,PPARG,and EGFR were screened out by the PPI network analysis on 88 common targets.The GO and KEGG pathway enrichment analysis showed that the inflammation,hormone balance,cell growth,proliferation,apoptosis,and oxidative stress are involved.Molecular docking studies have confirmed the high binding affinity between core active compounds and key targets.The drug similarity assessment on these core compounds suggested that they have the potential to be used as potential hair loss treatment drugs.This study elucidates the complex molecular mechanism of ASE in treating hair loss,and provides a reference for the future applications in hair care products.展开更多
Objective Traditional Chinese medicine(TCM)constitutes a valuable cultural heritage and an important source of antitumor compounds.Poria(Poria cocos(Schw.)Wolf),the dried sclerotium of a polyporaceae fungus,was first ...Objective Traditional Chinese medicine(TCM)constitutes a valuable cultural heritage and an important source of antitumor compounds.Poria(Poria cocos(Schw.)Wolf),the dried sclerotium of a polyporaceae fungus,was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia.Traditionally recognized for its diuretic,spleen-tonifying,and sedative properties,modern pharmacological studies confirm that Poria exhibits antioxidant,anti-inflammatory,antibacterial,and antitumor activities.Pachymic acid(PA;a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid),isolated from Poria,is a principal bioactive constituent.Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms,though these remain incompletely characterized.Neuroblastoma(NB),a highly malignant pediatric extracranial solid tumor accounting for 15%of childhood cancer deaths,urgently requires safer therapeutics due to the limitations of current treatments.Although PA shows multi-mechanistic antitumor potential,its efficacy against NB remains uncharacterized.This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking,dynamic simulations,and in vitro assays,aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays.Methods This study employed network pharmacology to identify potential targets of PA in NB,followed by validation using molecular docking,molecular dynamics(MD)simulations,MM/PBSA free energy analysis,RT-qPCR and Western blot experiments.Network pharmacology analysis included target screening via TCMSP,GeneCards,DisGeNET,SwissTargetPrediction,SuperPred,and PharmMapper.Subsequently,potential targets were predicted by intersecting the results from these databases via Venn analysis.Following target prediction,topological analysis was performed to identify key targets using Cytoscape software.Molecular docking was conducted using AutoDock Vina,with the binding pocket defined based on crystal structures.MD simulations were performed for 100 ns using GROMACS,and RMSD,RMSF,SASA,and hydrogen bonding dynamics were analyzed.MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex.In vitro validation included RT-qPCR and Western blot,with GAPDH used as an internal control.Results The CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability.GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress,vesicle lumen,and protein tyrosine kinase activity.KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT,MAPK,and Ras signaling pathways.Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1,EGFR,SRC,and HSP90AA1.RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1,EGFR,and SRC while increasing the HSP90AA1 mRNA and protein levels.Conclusion It was suggested that PA may exert its anti-NB effects by inhibiting AKT1,EGFR,and SRC expression,potentially modulating the PI3K/AKT signaling pathway.These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.展开更多
[Objectives]To investigate the antibacterial mechanism of Common Cnidium Fruit using network pharmacology.[Methods]Active components and targets of Common Cnidium Fruit were screened and obtained using the TCMSP datab...[Objectives]To investigate the antibacterial mechanism of Common Cnidium Fruit using network pharmacology.[Methods]Active components and targets of Common Cnidium Fruit were screened and obtained using the TCMSP database and HIT2.0 database.The collected targets were intersected with antibacterial/bacteriostatic targets obtained from the GeneCards database and OMIM database to identify the antibacterial/bacteriostatic targets of Common Cnidium Fruit.The active component-target network diagram of Common Cnidium Fruit was constructed using Cytoscape software and topological analysis was performed.GO enrichment analysis was performed on the target genes using the DAVID database.[Results]Screening yielded 25 active components of Common Cnidium Fruit,corresponding to 77 targets.Analysis identified 25 core antibacterial/bacteriostatic targets for Common Cnidium Fruit.Network analysis indicated that Common Cnidium Fruit may exert antibacterial/bacteriostatic effects through active components such asβ-sitosterol,stigmasterol,and xanthoxylin,while activating the body's immune regulatory functions by acting on targets including CASP3,PTGS2,BCL2,JUN,and ESR1.[Conclusions]Common Cnidium Fruit may exert antibacterial/bacteriostatic effects through multiple pathways via a mechanism involving multiple components,multiple targets,and multiple pathways.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
OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determ...OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determined via linear ion trap/electrostatic field orbital trap tandem highresolution mass spectrometry,and the identified compounds were performed network pharmacological analysis to predict possible pathways of the effects of GL on CP.A CP rat model was established by carrageenan,and rats were randomly assigned into a Control group,Sham group,CP group,GL low dose(3.5 g/kg)group,GL medium dose(7 g/kg)group,and GL high dose(14 g/kg)group.Hematoxylin-eosin staining of the prostate,and prostate blood-perfusion measured by laser speckle contrast analysis were used to evaluate the efficacy of GL.Expression of intercellular cell adhesion molecule-1(ICAM-1)and induce nitric oxide synthase(i NOS)were determined by immunohistochemistry,and the content of interferon-γ(IFN-γ),interleukin-1β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),chemokine ligand 1(CXCL1)and tumor necrosis factor-α(TNF-α)were determined by electro-chemiluminescence assays.The expression of p38 mitogen-activated protein kinase(p38 MAPK),phosphatidylinositol 3-kinase(PI3K),ribosomeassociated complex-alpha serine/threonine-protein kinase(Akt),nuclear factor-κ-gene binding p65(NF-κB p65),inhibitor of NF-κB-α(IκBα),glycogen synthase kinase-3β(GSK-3β),and their phosphorylated forms were tested by Western blot.RESULTS:In GL,a total of 48 compounds were identified,including 14 flavonoids,14 alkaloids,11 carboxylic acids,4 lactones,2 glycosides,2 terpenoids and 1 aldehyde.Network pharmacological analysis suggested that the mechanism of GL may be related to PI3K-Akt signaling pathway and cytokine expression.After treatment with GL,inflammatory pathological changes in the prostate of rats were significantly improved,and blood perfusion of the prostate was significantly decreased.GL reduced the expression of IFN-γ,CXCL1,TNF-α,IL-1β,i NOS,ICAM-1,p38 MAPK,p-p38 MAPK,PI3K,p-PI3K,NF-κB,p-NF-κB,IκBα,p-IκBα,GSK-3β,p-GSK-3β,p-Akt in CP rats,and increased the expression of IL-4 and IL-10 in CP rats.CONCLUSION:The chemical compositions of GL were first identified.GL can improve pathological changes in the prostate and recover the prostate blood perfusion of CP rats.The possible mechanisms of GL on CP involve increasing the expression of anti-inflammatory cytokines IL-4 and IL-10,inhibiting pro-inflammatory cytokines TNF-α,IL-1β,and IFN-γ,and down regulating the expression of CXCL1,i NOS,and ICAM-1 via inhibiting PI3K-Akt and NF-κB signaling pathway.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
OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Avail...OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target proteins of MT were retrieved from the GeneCards,PharmGkb,Therapeutic Target Database,DrugBank,and Online Mendelian Inheritance in Man databases.Information regarding MT and the drug targets was compared to obtain overlapping elements.This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram.Then,a“component-target”network diagram was constructed using screened drug components and target information,via Cytoscape(Institute for Systems Biology,Seattle,WA,USA).The database for annotation,visualization,and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses.Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.RESULTS:Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory,apoptosis,and nuclear factor kappa B(NF-κB)signaling pathways.Berberine(BBR),one of the main components of HLD,inhibited the development of MT in mice.BBR reduced cell viability while increasing B-cell lymphoma 2(Bcl-2)protein expression and decreasing CD86,NF-κB,Bax,and Caspase-3 protein expression in brain vascular 2(BV2)mcroglia cells treated with morphine.Additionally,BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.CONCLUSIONS:BBR,a key component of HLD,effectively suppressed microglial activation and neuroinflammation by regulating the NF-κB and apoptosis signaling pathways,thereby delaying MT.This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.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
BACKGROUND Camellia luteoflora is a unique variety of Camellia in China which is only distributes in Chishui City,Guizhou Province and Luzhou City,Sichuan Province.Its dried leaves are used by local residents as tea t...BACKGROUND Camellia luteoflora is a unique variety of Camellia in China which is only distributes in Chishui City,Guizhou Province and Luzhou City,Sichuan Province.Its dried leaves are used by local residents as tea to drink with light yellow and special aroma for health care.It has high potential economic medicinal value.Colon adenocarcinoma(COAD)is the third most frequent malignancy and its incidence and mortality is increasing.However,the current common treatments for COAD bring great side effects.In recent years,natural products and their various de-rivatives have shown significant potential to supplement conventional therapies and to reduce associated toxicity while improving efficacy.In order to overcome the limitations of traditional treatment methods,the global demand and development of natural anti-COAD drugs were increasingly hindered.AIM To investigate the potential targets and mechanisms of Camellia luteoflora anti-COAD.METHODS Nuclear magnetic resonance and mass spectrometry was used to identified the compounds of Camellia luteoflora.Network pharmacology analysis and survival analysis was used in this study to investigate the anti-COAD effect and mechanism of Camellia luteoflora.RESULTS Firstly,a total of 13 compounds were identified.Secondly,10 active ingredients for 204 potential targets were screened and protein-protein interaction analysis showed that TP53,STAT3,ESR1,MAPK8,AKR1C3,RELA,CYP19A1,CYP1A1,JUN and CYP17A1 were hub targets.GO and KEGG enrichment analyses revealed that Camellia luteoflora exerted anti-COAD effect through multiple functions and pathways.Then,the analysis of survival and stage indicated that TP53 was highly expressed in COAD and the overall survival of high-TP53 and high-CYP19A1 COAD patients was significantly shorter than the low group and there was significant difference in MAPK and RELA expression between different stages.Finally,the molecular docking results demonstrated the binding affinities and sites between active ingredients and TP53,STAT3,ESR1.CONCLUSION Our study systematically demonstrated the potential anti-COAD mechanism of Camellia luteoflora and provided a theoretical basis for its further application in the COAD treatment.展开更多
To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmac...To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmacology and molecular docking methods.Disease-associated targets for gout and hyperuricemia were identified from the GeneCards,OMIM,Disgenet,and TTD databases,while the key active components and their corresponding targets for Smilax Glabra and Semen Coicis were obtained from the TCSMP database.The intersection of these targets enabled the construction of a protein-protein interaction(PPI)network,which was subsequently visualized and analyzed.Core targets were further subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to elucidate the biological processes and pathways involved.Molecular docking was then employed to validate the reliability of the interactions between the active components and the identified targets.The analysis revealed that Smilax Glabra and Semen Coicis contained 15 bioactive components that interacted with 393 potential targets,while gout and hyperuricemia were associated with 660 targets in total.The primary active compounds implicated in treating these conditions included diosgenin,quercetin,and naringenin,which were found to interact with crucial hub targets such as BCL2,CASP3,and MAPK3.These interactions suggested that the herbal medicine pair modulated several biological processes,including gland development and the regulation of body fluid levels,through pathways involving membrane rafts,membrane microdomains,and nuclear receptor activities.Enrichment analyses highlighted their involvement in multiple signaling pathways,such as EGFR tyrosine kinase inhibitor resistance,phospholipase D signaling,and platelet activation.Molecular docking confirmed the strong binding affinities between the hub genes and the major active components,supporting their potential role in therapeutic efficacy.This study demonstrated that Smilax Glabra and Semen Coicis might offer a promising therapeutic strategy for gout and hyperuricemia by targeting multiple molecular components,biological functions,and pathways.The findings underscored the unique potential of traditional Chinese medicine(TCM)in managing complex diseases by leveraging synergistic effects across diverse biological mechanisms.展开更多
Soybean is widely used in diets,and numerous reports have highlighted its antioxidant properties.However,constructing a methodology for rapid identifying and predicting a series of antioxidant active ingredients in So...Soybean is widely used in diets,and numerous reports have highlighted its antioxidant properties.However,constructing a methodology for rapid identifying and predicting a series of antioxidant active ingredients in Soybean presents certain challenges.Therefore,we introduced the spectrum-effect relationship-ingredient knockout identification technique to identify a series of antioxidant active ingredients in soybean.By combining untargeted metabolomics with network pharmacology,we predicted the antioxidant active ingredients and their target sites.We successfully identified 4 antioxidant active compounds(daidzein,genistein,daidzein,and glycitin)and 10 corresponding antioxidant targets(epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),steroid receptor coactivator(SRC),tumor necrosis factor(TNF),kinase insert domain receptor(KDR),AKT serine/threonine kinase 1(AKT1),growth factor receptor bound protein 2(GRB2),signal transducer and activator of transcription1(STAT1),mitogen-activated protein kinase 8(MAPK8),B-cell lymphoma-2(BCL2))by our analysis.The validation results from cell experiments revealed that glycitin exhibited the best antioxidant activity and significantly influenced the expression of EGFR and the proteins associated with nuclear factor erythroid 2-related factor 2/NAD(P)H quinone dehydrogenase 1(NRF2/NQO1)signaling pathways.These findings were consistent with the predicted outcomes and were further confirmed in a zebrafish model.It suggests that glycitin may exert antioxidant effects by regulating the expression of EGFR,NRF2,and NQO1 proteins.The results demonstrate that a rapid analytical method for determining antioxidant activity was established.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
Traditional Chinese medicine(TCM)demonstrates distinctive advantages in disease prevention and treatment.However,analyzing its biological mechanisms through the modern medical research paradigm of“single drug,single ...Traditional Chinese medicine(TCM)demonstrates distinctive advantages in disease prevention and treatment.However,analyzing its biological mechanisms through the modern medical research paradigm of“single drug,single target”presents significant challenges due to its holistic approach.Network pharmacology and its core theory of network targets connect drugs and diseases from a holistic and systematic perspective based on biological networks,overcoming the limitations of reductionist research models and showing considerable value in TCM research.Recent integration of network target computational and experimental methods with artificial intelligence(AI)and multi-modal multi-omics technologies has substantially enhanced network pharmacology methodology.The advancement in computational and experimental techniques provides complementary support for network target theory in decoding TCM principles.This review,centered on network targets,examines the progress of network target methods combined with AI in predicting disease molecular mechanisms and drug-target relationships,alongside the application of multi-modal multi-omics technologies in analyzing TCM formulae,syndromes,and toxicity.Looking forward,network target theory is expected to incorporate emerging technologies while developing novel approaches aligned with its unique characteristics,potentially leading to significant breakthroughs in TCM research and advancing scientific understanding and innovation in TCM.展开更多
文摘1.Discipline origins In 1984,“analytical pharmacology”was firstly used in the paper entitled“The future of analytical pharmacologyda personal view”by Dr.J.S.Cridland,director of a clinical pharmacological laboratory at Department of Pharmacology,University of Cape Town.He proposed“Analytical pharmacology is at present usually a tool of clinical pharmacology”,which is mainly used for therapeutic drug monitoring,analysis of clinical pharmacokinetics,and toxicological screening to provide a basis for reasonable medication and clinical dose adjustment[1].In 1984,W.J.Black,Director of Wellcome Research Laboratories,was offered a personal Chair at King's College Hospital School of Medicine and Dentistry,part of King's College London.He chose“Analytical Pharmacology”as a title for the Chair[2].
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supported by the National Key Research and Development Project(2022YFC3400700)the City-School Cooperation Project of the Fuyang Science and Technology Special Fund undertaken by Fuyang Normal University(SXHZ2020007)+1 种基金the Basic Research Program of Shenzhen Municipal Government(JCYJ20200109114242138)the Special Commissioner for Rural Science and Technology of Guangdong Province(KTP20210345).
文摘Background Meat originating from the spent hen is an important source of poultry meat production;however,multiple factors cause the decline in the meat quality of spent hens.Chinese herbs have been widely used as medi-cine for a long time to prevent diseases and as nutrient supplements to improve the product quality.This experi-ment explored the effects of adding 1.0%Chinese herbal formula(CHF,including 0.30%Leonurus japonicus Houtt.,0.20%Salvia miltiorrhiza Bge.,0.25%Ligustrum lucidum Ait.,and 0.25%Taraxacum mongolicum Hand.-Mazz.)for 120 d to the spent hens’diet through metabolomics,network pharmacology,and microbiome strategies.Results The results indicated that CHF supplementation improved the meat quality by reducing drip loss(P<0.05),b*value(P=0.058),and shear force(P=0.099)and increasing cooked meat percentage(P=0.054)and dry matter(P<0.05)of breast muscle.The addition of CHF improved the nutritional value of breast muscle by increasing(P<0.05)the content of C18:2n-6,n-6/n-3 polyunsaturated fatty acids(PUFA),total PUFA,PUFA-to-saturated fatty acids(SFA)ratio,and hypocholesterolemic-to-hypercholesterolemic ratio,and tending to increase serine content(P=0.069).The targeted metabolomics analysis revealed that the biosynthesis of SFA,linoleic acid metabolism,fatty acid degradation,fatty acid elongation,and fatty acid biosynthesis pathways were enriched by CHF supplementation.Furthermore,the network pharmacology analysis indicated that CHF was closely associated with oxidative stress and lipid metabo-lism.The CHF supplementation increased the glutathione peroxidase level(P<0.05)and upregulated gene expres-sion related to the Nrf2 pathway(including HO-1,P<0.05;Nrf2,P=0.098;CAT,P=0.060;GPX1,P=0.063;and SOD2,P=0.052)and lipid metabolism(including PPARγ,P<0.05;SREBP1,P=0.059;and CPT1A,P=0.058).Additionally,CHF supplementation increased Firmicutes and decreased Bacteroidetes,Spirochaetes,and Synergistetes abundances(P<0.05),which may contribute to better meat quality.Conclusions Our results suggest that CHF supplementation improved the quality and nutritional value of meat,which will provide a theoretical basis for the utilization of CHF as a feed additive in spent hens’diets.
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supported by the National Medical Products Administration Commissioned Research Project (No.20211440216)the National Administration of Traditional Chinese Medicine Science and Technology Project (No.GZY-KJS-2024-03)+3 种基金the State Key Laboratory of Drug Regulatory Science Project (No.2023SKLDRS0104)the Basic Research Program Natural Science Fund-Frontier Leading Technology Basic Research Special Project of Jiangsu Province (No.BK20232014)the Programs Foundation for Leading Talents in National Administration of Traditional Chinese Medicine of China“Qihuang scholars”Projectthe Tianjin Administration for Market Regulation Science and Technology Key Projects (No.2022-W35)。
文摘The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three Combinations”).However,considering TCM's distinctive features of“syndrome differentiation and treatment”and“multicomponent formulations and complex mechanisms”,current TCM drug development faces challenges such as insufficient understanding of the material basis and the overall mechanism of action and an incomplete evidence chain system.Moreover,significant obstacles persist in gathering human experience data,evaluating clinical efficacy,and controlling the quality of active ingredients,which impede the innovation process in TCM drug development.Network pharmacology,centered on the“network targets”theory,transcends the limitations of the conventional“single target”reductionist research model.It emphasizes the comprehensive effects of disease or syndrome biological networks as targets to elucidate the overall regulatory mechanism of TCM prescriptions.This approach aligns with the holistic perspective of TCM,offering a novel method consistent with TCM's holistic view for investigating the complex mechanisms of TCM and developing new TCM drugs.It is internationally recognized as a“next-generation drug research model”.To advance the research of new tools,methods,and standards for TCM evaluation and to overcome fundamental,critical,and cutting-edge technical challenges in TCM regulation,this consensus aims to explore the characteristics,progress,challenges,applicable pathways,and specific applications of network pharmacology as a new theory,method,and tool in TCM drug development.The goal is to enhance the quality of TCM drug research and development and accelerate the efficiency of developing new TCM products.
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The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,and the network pharmacology was used to elucidate their anti-hair loss mechanism,which was verified by molecular docking technology.572 active compounds were identified from the ASE by metabolomics methods,where there are 1447 corresponding targets and 492 targets related to hair loss,totaling 88 targets.20 core active substances were identified by constructing a network between common targets and active substances,which include vanillic acid,chorionic acid,caffeic acid and apigenin.The five key targets of TNF,TP53,IL6,PPARG,and EGFR were screened out by the PPI network analysis on 88 common targets.The GO and KEGG pathway enrichment analysis showed that the inflammation,hormone balance,cell growth,proliferation,apoptosis,and oxidative stress are involved.Molecular docking studies have confirmed the high binding affinity between core active compounds and key targets.The drug similarity assessment on these core compounds suggested that they have the potential to be used as potential hair loss treatment drugs.This study elucidates the complex molecular mechanism of ASE in treating hair loss,and provides a reference for the future applications in hair care products.
文摘Objective Traditional Chinese medicine(TCM)constitutes a valuable cultural heritage and an important source of antitumor compounds.Poria(Poria cocos(Schw.)Wolf),the dried sclerotium of a polyporaceae fungus,was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia.Traditionally recognized for its diuretic,spleen-tonifying,and sedative properties,modern pharmacological studies confirm that Poria exhibits antioxidant,anti-inflammatory,antibacterial,and antitumor activities.Pachymic acid(PA;a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid),isolated from Poria,is a principal bioactive constituent.Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms,though these remain incompletely characterized.Neuroblastoma(NB),a highly malignant pediatric extracranial solid tumor accounting for 15%of childhood cancer deaths,urgently requires safer therapeutics due to the limitations of current treatments.Although PA shows multi-mechanistic antitumor potential,its efficacy against NB remains uncharacterized.This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking,dynamic simulations,and in vitro assays,aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays.Methods This study employed network pharmacology to identify potential targets of PA in NB,followed by validation using molecular docking,molecular dynamics(MD)simulations,MM/PBSA free energy analysis,RT-qPCR and Western blot experiments.Network pharmacology analysis included target screening via TCMSP,GeneCards,DisGeNET,SwissTargetPrediction,SuperPred,and PharmMapper.Subsequently,potential targets were predicted by intersecting the results from these databases via Venn analysis.Following target prediction,topological analysis was performed to identify key targets using Cytoscape software.Molecular docking was conducted using AutoDock Vina,with the binding pocket defined based on crystal structures.MD simulations were performed for 100 ns using GROMACS,and RMSD,RMSF,SASA,and hydrogen bonding dynamics were analyzed.MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex.In vitro validation included RT-qPCR and Western blot,with GAPDH used as an internal control.Results The CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability.GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress,vesicle lumen,and protein tyrosine kinase activity.KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT,MAPK,and Ras signaling pathways.Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1,EGFR,SRC,and HSP90AA1.RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1,EGFR,and SRC while increasing the HSP90AA1 mRNA and protein levels.Conclusion It was suggested that PA may exert its anti-NB effects by inhibiting AKT1,EGFR,and SRC expression,potentially modulating the PI3K/AKT signaling pathway.These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.
基金Supported by Scientific Research Platform Project of Putuo District,Shanghai(2024QX04).
文摘[Objectives]To investigate the antibacterial mechanism of Common Cnidium Fruit using network pharmacology.[Methods]Active components and targets of Common Cnidium Fruit were screened and obtained using the TCMSP database and HIT2.0 database.The collected targets were intersected with antibacterial/bacteriostatic targets obtained from the GeneCards database and OMIM database to identify the antibacterial/bacteriostatic targets of Common Cnidium Fruit.The active component-target network diagram of Common Cnidium Fruit was constructed using Cytoscape software and topological analysis was performed.GO enrichment analysis was performed on the target genes using the DAVID database.[Results]Screening yielded 25 active components of Common Cnidium Fruit,corresponding to 77 targets.Analysis identified 25 core antibacterial/bacteriostatic targets for Common Cnidium Fruit.Network analysis indicated that Common Cnidium Fruit may exert antibacterial/bacteriostatic effects through active components such asβ-sitosterol,stigmasterol,and xanthoxylin,while activating the body's immune regulatory functions by acting on targets including CASP3,PTGS2,BCL2,JUN,and ESR1.[Conclusions]Common Cnidium Fruit may exert antibacterial/bacteriostatic effects through multiple pathways via a mechanism involving multiple components,multiple targets,and multiple pathways.
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National Major Scientific and the Technological Special Project:Establishment of a Clinically Oriented Preclinical Research and Development Technology Platform for New Chinese Medicines based on Famous Doctors'Prescriptions(No.2017ZX09301011)"Decoding Traditional Chinese Medicine"Project of Beijing University of Chinese Medicine:New Drugs Research and Development of Chinese Medicine based on Famous Doctors and Famous Prescriptions(No.90010961020020)the Horizontal Project:Preclinical Pharmacology and Pharmacodynamic Research of a New Chinese Medicine—Guilong Granules(No.2016110031007799)。
文摘OBJECTIVE:To investigate the protective effects of Guilong prescription(归龙方,GL)on chronic prostatitis(CP)and unravel the underlying mechanisms of its pharmacological effects.METHODS:The composition of GL was determined via linear ion trap/electrostatic field orbital trap tandem highresolution mass spectrometry,and the identified compounds were performed network pharmacological analysis to predict possible pathways of the effects of GL on CP.A CP rat model was established by carrageenan,and rats were randomly assigned into a Control group,Sham group,CP group,GL low dose(3.5 g/kg)group,GL medium dose(7 g/kg)group,and GL high dose(14 g/kg)group.Hematoxylin-eosin staining of the prostate,and prostate blood-perfusion measured by laser speckle contrast analysis were used to evaluate the efficacy of GL.Expression of intercellular cell adhesion molecule-1(ICAM-1)and induce nitric oxide synthase(i NOS)were determined by immunohistochemistry,and the content of interferon-γ(IFN-γ),interleukin-1β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),chemokine ligand 1(CXCL1)and tumor necrosis factor-α(TNF-α)were determined by electro-chemiluminescence assays.The expression of p38 mitogen-activated protein kinase(p38 MAPK),phosphatidylinositol 3-kinase(PI3K),ribosomeassociated complex-alpha serine/threonine-protein kinase(Akt),nuclear factor-κ-gene binding p65(NF-κB p65),inhibitor of NF-κB-α(IκBα),glycogen synthase kinase-3β(GSK-3β),and their phosphorylated forms were tested by Western blot.RESULTS:In GL,a total of 48 compounds were identified,including 14 flavonoids,14 alkaloids,11 carboxylic acids,4 lactones,2 glycosides,2 terpenoids and 1 aldehyde.Network pharmacological analysis suggested that the mechanism of GL may be related to PI3K-Akt signaling pathway and cytokine expression.After treatment with GL,inflammatory pathological changes in the prostate of rats were significantly improved,and blood perfusion of the prostate was significantly decreased.GL reduced the expression of IFN-γ,CXCL1,TNF-α,IL-1β,i NOS,ICAM-1,p38 MAPK,p-p38 MAPK,PI3K,p-PI3K,NF-κB,p-NF-κB,IκBα,p-IκBα,GSK-3β,p-GSK-3β,p-Akt in CP rats,and increased the expression of IL-4 and IL-10 in CP rats.CONCLUSION:The chemical compositions of GL were first identified.GL can improve pathological changes in the prostate and recover the prostate blood perfusion of CP rats.The possible mechanisms of GL on CP involve increasing the expression of anti-inflammatory cytokines IL-4 and IL-10,inhibiting pro-inflammatory cytokines TNF-α,IL-1β,and IFN-γ,and down regulating the expression of CXCL1,i NOS,and ICAM-1 via inhibiting PI3K-Akt and NF-κB signaling pathway.
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Natural Science Foundation-funded Project:Study on the Mechanism of Mechanical Stress Sensing Element Piezo Type Mechanosensitive Ion Channel Component 2 Interacting with Nuclear Receptor Subfamily 4 Group A Member 2 Mediating Traumatic Brain Injury(No.82172190)。
文摘OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target proteins of MT were retrieved from the GeneCards,PharmGkb,Therapeutic Target Database,DrugBank,and Online Mendelian Inheritance in Man databases.Information regarding MT and the drug targets was compared to obtain overlapping elements.This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram.Then,a“component-target”network diagram was constructed using screened drug components and target information,via Cytoscape(Institute for Systems Biology,Seattle,WA,USA).The database for annotation,visualization,and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses.Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.RESULTS:Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory,apoptosis,and nuclear factor kappa B(NF-κB)signaling pathways.Berberine(BBR),one of the main components of HLD,inhibited the development of MT in mice.BBR reduced cell viability while increasing B-cell lymphoma 2(Bcl-2)protein expression and decreasing CD86,NF-κB,Bax,and Caspase-3 protein expression in brain vascular 2(BV2)mcroglia cells treated with morphine.Additionally,BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.CONCLUSIONS:BBR,a key component of HLD,effectively suppressed microglial activation and neuroinflammation by regulating the NF-κB and apoptosis signaling pathways,thereby delaying MT.This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.
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.
基金Supported by Guizhou Provincial Basic Research Program(Natural Science),No.ZK[2023]-554and the National Natural Science Foundation of China,No.32360144.
文摘BACKGROUND Camellia luteoflora is a unique variety of Camellia in China which is only distributes in Chishui City,Guizhou Province and Luzhou City,Sichuan Province.Its dried leaves are used by local residents as tea to drink with light yellow and special aroma for health care.It has high potential economic medicinal value.Colon adenocarcinoma(COAD)is the third most frequent malignancy and its incidence and mortality is increasing.However,the current common treatments for COAD bring great side effects.In recent years,natural products and their various de-rivatives have shown significant potential to supplement conventional therapies and to reduce associated toxicity while improving efficacy.In order to overcome the limitations of traditional treatment methods,the global demand and development of natural anti-COAD drugs were increasingly hindered.AIM To investigate the potential targets and mechanisms of Camellia luteoflora anti-COAD.METHODS Nuclear magnetic resonance and mass spectrometry was used to identified the compounds of Camellia luteoflora.Network pharmacology analysis and survival analysis was used in this study to investigate the anti-COAD effect and mechanism of Camellia luteoflora.RESULTS Firstly,a total of 13 compounds were identified.Secondly,10 active ingredients for 204 potential targets were screened and protein-protein interaction analysis showed that TP53,STAT3,ESR1,MAPK8,AKR1C3,RELA,CYP19A1,CYP1A1,JUN and CYP17A1 were hub targets.GO and KEGG enrichment analyses revealed that Camellia luteoflora exerted anti-COAD effect through multiple functions and pathways.Then,the analysis of survival and stage indicated that TP53 was highly expressed in COAD and the overall survival of high-TP53 and high-CYP19A1 COAD patients was significantly shorter than the low group and there was significant difference in MAPK and RELA expression between different stages.Finally,the molecular docking results demonstrated the binding affinities and sites between active ingredients and TP53,STAT3,ESR1.CONCLUSION Our study systematically demonstrated the potential anti-COAD mechanism of Camellia luteoflora and provided a theoretical basis for its further application in the COAD treatment.
文摘To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmacology and molecular docking methods.Disease-associated targets for gout and hyperuricemia were identified from the GeneCards,OMIM,Disgenet,and TTD databases,while the key active components and their corresponding targets for Smilax Glabra and Semen Coicis were obtained from the TCSMP database.The intersection of these targets enabled the construction of a protein-protein interaction(PPI)network,which was subsequently visualized and analyzed.Core targets were further subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to elucidate the biological processes and pathways involved.Molecular docking was then employed to validate the reliability of the interactions between the active components and the identified targets.The analysis revealed that Smilax Glabra and Semen Coicis contained 15 bioactive components that interacted with 393 potential targets,while gout and hyperuricemia were associated with 660 targets in total.The primary active compounds implicated in treating these conditions included diosgenin,quercetin,and naringenin,which were found to interact with crucial hub targets such as BCL2,CASP3,and MAPK3.These interactions suggested that the herbal medicine pair modulated several biological processes,including gland development and the regulation of body fluid levels,through pathways involving membrane rafts,membrane microdomains,and nuclear receptor activities.Enrichment analyses highlighted their involvement in multiple signaling pathways,such as EGFR tyrosine kinase inhibitor resistance,phospholipase D signaling,and platelet activation.Molecular docking confirmed the strong binding affinities between the hub genes and the major active components,supporting their potential role in therapeutic efficacy.This study demonstrated that Smilax Glabra and Semen Coicis might offer a promising therapeutic strategy for gout and hyperuricemia by targeting multiple molecular components,biological functions,and pathways.The findings underscored the unique potential of traditional Chinese medicine(TCM)in managing complex diseases by leveraging synergistic effects across diverse biological mechanisms.
基金supported by National Key R&D Program of China(2022YFF1100300)Joint Fund of Henan Province Science and Technology R&D Program(235200810051)+1 种基金Key Project in Science and Technology Agency of Henan Province(242102310561)key research projects of higher education institutions in Henan Province(24B350002).
文摘Soybean is widely used in diets,and numerous reports have highlighted its antioxidant properties.However,constructing a methodology for rapid identifying and predicting a series of antioxidant active ingredients in Soybean presents certain challenges.Therefore,we introduced the spectrum-effect relationship-ingredient knockout identification technique to identify a series of antioxidant active ingredients in soybean.By combining untargeted metabolomics with network pharmacology,we predicted the antioxidant active ingredients and their target sites.We successfully identified 4 antioxidant active compounds(daidzein,genistein,daidzein,and glycitin)and 10 corresponding antioxidant targets(epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),steroid receptor coactivator(SRC),tumor necrosis factor(TNF),kinase insert domain receptor(KDR),AKT serine/threonine kinase 1(AKT1),growth factor receptor bound protein 2(GRB2),signal transducer and activator of transcription1(STAT1),mitogen-activated protein kinase 8(MAPK8),B-cell lymphoma-2(BCL2))by our analysis.The validation results from cell experiments revealed that glycitin exhibited the best antioxidant activity and significantly influenced the expression of EGFR and the proteins associated with nuclear factor erythroid 2-related factor 2/NAD(P)H quinone dehydrogenase 1(NRF2/NQO1)signaling pathways.These findings were consistent with the predicted outcomes and were further confirmed in a zebrafish model.It suggests that glycitin may exert antioxidant effects by regulating the expression of EGFR,NRF2,and NQO1 proteins.The results demonstrate that a rapid analytical method for determining antioxidant activity was established.
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.
文摘Traditional Chinese medicine(TCM)demonstrates distinctive advantages in disease prevention and treatment.However,analyzing its biological mechanisms through the modern medical research paradigm of“single drug,single target”presents significant challenges due to its holistic approach.Network pharmacology and its core theory of network targets connect drugs and diseases from a holistic and systematic perspective based on biological networks,overcoming the limitations of reductionist research models and showing considerable value in TCM research.Recent integration of network target computational and experimental methods with artificial intelligence(AI)and multi-modal multi-omics technologies has substantially enhanced network pharmacology methodology.The advancement in computational and experimental techniques provides complementary support for network target theory in decoding TCM principles.This review,centered on network targets,examines the progress of network target methods combined with AI in predicting disease molecular mechanisms and drug-target relationships,alongside the application of multi-modal multi-omics technologies in analyzing TCM formulae,syndromes,and toxicity.Looking forward,network target theory is expected to incorporate emerging technologies while developing novel approaches aligned with its unique characteristics,potentially leading to significant breakthroughs in TCM research and advancing scientific understanding and innovation in TCM.
