To explore the material basis and mechanisms of the anti-inflammatory effects of Hibiscus mutabilis L..The active ingredients and potential targets of Hibiscus mutabilis L.were obtained through the literature review a...To explore the material basis and mechanisms of the anti-inflammatory effects of Hibiscus mutabilis L..The active ingredients and potential targets of Hibiscus mutabilis L.were obtained through the literature review and SwissADME platform.Genes related to the inflammation were collected using Genecards and OMIM databases,and the intersection genes were submitted on STRING and DAVID websites.Then,the protein interaction network(PPI),gene ontology(GO)and pathway(KEGG)were analyzed.Cytoscape 3.7.2 software was used to construct the“Hibiscus mutabilis L.-active ingredient-target-inflammation”network diagram,and AutoDockTools-1.5.6 software was used for the molecular docking verification.The antiinflammatory effect of Hibiscus mutabilis L.active ingredient was verified by the RAW264.7 inflammatory cell model.The results showed that 11 active components and 94 potential targets,1029 inflammatory targets and 24 intersection targets were obtained from Hibiscus mutabilis L..The key anti-inflammatory active ingredients of Hibiscus mutabilis L.are quercetin,apigenin and luteolin.Its action pathway is mainly related to NF-κB,cancer pathway and TNF signaling pathway.Cell experiments showed that total flavonoids of Hibiscus mutabilis L.could effectively inhibit the expression of tumor necrosis factor(TNF-α),interleukin 8(IL-8)and epidermal growth factor receptor(EGFR)in LPS-induced RAW 264.7 inflammatory cells.It also downregulates the phosphorylation of human nuclear factor ĸB inhibitory protein α(IĸBα)and NF-κB p65 subunit protein(p65).Overall,the anti-inflammatory effect of Hibiscus mutabilis L.is related to many active components,many signal pathways and targets,which provides a theoretical basis for its further development and application.展开更多
Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-relate...Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-related diseases like Alzheimer’s disease,osteoporosis,low immunity,glucose and lipid metabolism disorders,and cardiovascular diseases.With the continuous increase of the elderly population,the pressure on the medical industry is increasing.To lower the burden on the medical industry and increase the average age of the elderly,it is vital to explore effective anti-aging materials.Ginseng Radix et Rhizoma(Renshen),as a traditional and precious Chinese medicinal herb,is known as the“king of all herbs”.It is famous for its effects of“tonifying Qi,restoring pulse”(helping with the generation of Qi(the fundamental,vital energy that continuously flows within the body)and the circulation of blood)and strengthening the body,nourishing the spleen and lungs,generating fluids and nourishing blood,calming the mind and improving intelligence.Recently,its anti-aging effect has received increasing attention from modern scientific research.This study summarizes the pharmacological effects of the main active ingredients of Renshen(ginsenosides,polysaccharides,etc.)on resisting aging,including preventing neuroaging,suppressing skin aging,mitigating ovarian aging,inhibiting osteoporosis and arthritis,enhancing the immune system of the elderly,protecting the cardiovascular system,resisting aging-induced fatigue and exerting the anti-tumor effects.Through network pharmacology and molecular docking,the anti-aging active ingredients of Renshen were screened,and the key targets and pathways of anti-aging active ingredients in Renshen were determined.Using network pharmacology,totally 106 drug targets and 3,479 disease targets were screened,and 79 common targets between aging and Renshen were identified.Three core targets were identified in the PPI network,including TNF,AKT1,and IL-1β.Molecular docking was used to obtain further verification.This study emphasizes the potential of Renshen as a source of anti-aging activity,which can be developed into a novel drug for the treatment of age-related diseases.展开更多
Background:Wenqing Yin(WQY)is a classic prescription used to treat skin diseases like atopic dermatitis(AD)in China,and the aim of this study is to investigate the therapeutic effects and molecular mechanisms of WQY o...Background:Wenqing Yin(WQY)is a classic prescription used to treat skin diseases like atopic dermatitis(AD)in China,and the aim of this study is to investigate the therapeutic effects and molecular mechanisms of WQY on AD.Methods:The DNFB-induced mouse models of AD were established to investigate the therapeutic effects of WQY on AD.The symptoms of AD in the ears and backs of the mice were assessed,while inflammatory factors in the ear were quantified using quantitative real-time-polymerase chain reaction(qRT-PCR),and the percentages of CD4^(+)and CD8^(+)cells in the spleen were analyzed through flow cytometry.The compounds in WQY were identified using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis and the key targets and pathways of WQY to treat AD were predicted by network pharmacology.Subsequently,the key genes were tested and verified by qRT-PCR,and the potential active components and target proteins were verified by molecular docking.Results:WQY relieved the AD symptoms and histopathological injuries in the ear and back skin of mice with AD.Meanwhile,WQY significantly reduced the levels of inflammatory factors IL-6 and IL-1βin ear tissue,as well as the ratio of CD4^(+)/CD8^(+)cells in spleen.Additionally,a total of 142 compounds were identified from the water extract of WQY by UPLC-Orbitrap-MS/MS.39 key targets related to AD were screened out by network pharmacology methods.The KEGG analysis indicated that the effects of WQY were primarily mediated through pathways associated with Toll-like receptor signaling and T cell receptor signaling.Moreover,the results of qRT-PCR demonstrated that WQY significantly reduced the mRNA expressions of IL-4,IL-10,GATA3 and FOXP3,and molecular docking simulation verified that the active components of WQY had excellent binding abilities with IL-4,IL-10,GATA3 and FOXP3 proteins.Conclusion:The present study demonstrated that WQY effectively relieved AD symptoms in mice,decreased the inflammatory factors levels,regulated the balance of CD4^(+)and CD8^(+)cells,and the mechanism may be associated with the suppression of Th2 and Treg cell immune responses.展开更多
The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains...The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains to be elucidated.Employing a network pharmacology and molecular docking approach,this study systematically investigated the synergistic mechanism of the herb pair DC and LR in RA treatment.Active components and their corresponding targets were retrieved from the TCMSP database and relevant literature,and RA-related targets were collected from established disease databases.A total of 73 overlapping targets between DC-LR and RA were identified,among which core targets such as AKT1,TNF,and CASP3 were highlighted.GO and KEGG enrichment analyses revealed that these targets are involved in biological processes such as oxidative stress response and cell migration,and are significantly enriched in key pathways including HIF-1,TNF,and PI3K-Akt signaling pathways.Compatibility analysis further revealed that the combination of DC and LR may enhance therapeutic effects through synergistic regulation of shared targets and complementary modulation of upstream and downstream pathway components.Molecular docking confirmed strong binding affinities between core active components and key targets.This study provides a multi-dimensional“component-target-pathway”perspective on the potential synergistic anti-RA mechanism of the DC-LR herb pair,offering a theoretical basis for further experimental validation and clinical application.展开更多
The gastroprotective activity of water extracts from Citrus reticulata'Chachi'leaves(JY)was investigated,and its potential action mechanisms were revealed using network pharmacology.First,the main chemical com...The gastroprotective activity of water extracts from Citrus reticulata'Chachi'leaves(JY)was investigated,and its potential action mechanisms were revealed using network pharmacology.First,the main chemical components of JY were identified using high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry,14 compounds were preliminarily identified,with flavonoids being the primary components.Next,the protective effect of JY on ethanol-induced damage was investigated in vitro.An MTT assay showed that JY could significantly promote the proliferation of GES-1 cells and reduce the damage caused by ethanol.A gastric ulcer model was induced in mice using ethanol,and JY(1,2,and 4 mg/kg)was orally administered to the mice to counteract ethanol-induced gastric ulcers.Pretreatment with JY reduced the severity of ethanol-induced gastric injury.Histopathological results showed that JY enhanced the cell structure of gastric tissue,increased the secretion of gastric mucosal mucus,and reduced gastric edema caused by ethanol injury.JY significantly decreased the levels of pro-inflammatory factors,including interleukin(IL)-1β,IL-6,and tumor necrosis factorα,in the serum.Additionally,JY increased the levels of prostaglandin E2 and the activity of total superoxide dismutase,while significantly reducing the levels of the lipid peroxidation product malondialdehyde in gastric tissue.In parallel,JY significantly upregulated the mRNA expressions of copper/zinc superoxide dismutase(Cu/Zn-SOD),manganese superoxide dismutase(Mn-SOD),and glutathione peroxidase(GPx)to alleviate oxidative stress.JY also promoted the healing of gastric ulcers by upregulating the mRNA expressions of vascular endothelial growth factor(VEGF)and epidermal growth factor receptor(EGFR).Finally,network pharmacology was used to analyze the potential bioactive substances in JY and their mechanisms.The results indicated that the protective effect of JY might be related to flavonoids and that JY exerts its gastroprotective effects by participating in the PI3K-Akt and VEGF signaling pathways.These findings suggest that JY could be a valuable natural resource for preventing ethanol-induced gastric injury.展开更多
This study explored the therapeutic targets and molecular mechanisms of Huangqi Guizhi Decoction (HGD) in alleviatingpulmonary embolism (PE) by employing network pharmacology and molecular docking techniques. Firstly,...This study explored the therapeutic targets and molecular mechanisms of Huangqi Guizhi Decoction (HGD) in alleviatingpulmonary embolism (PE) by employing network pharmacology and molecular docking techniques. Firstly, the effective activecomponents of the Chinese herbs in HGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and their potential therapeutic targets were predicted using the Swiss Target Prediction platform. Subsequently, PErelatedtarget genes were obtained from the Online Mendelian Inheritance in Man (OMIM) database and GeneCards database.Then, the Wei Sheng Xin tool was used to generate a Venn diagram for identifying the common targets between the herb-relatedtargets and PE-related targets. After screening these common targets, a “drug-component-target network” and a protein-proteininteraction (PPI) network were constructed. Furthermore, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia ofGenes and Genomes (KEGG) enrichment analysis were conducted on the intersecting targets, and molecular docking verificationwas performed using AutoDockTools and PyMol software. Finally, 20 active components were screened from Astragali Radix, 7from Cinnamomi Ramulus, 13 from Paeoniae Radix Alba, 5 from Zingiberis Rhizoma Recens, and 29 from Jujubae Fructus, witha total of 983 therapeutic targets. Among these targets, 134 were associated with PE, and protein kinase B1 (AKT1), mitogenactivatedprotein kinase 1 (MAPK1), and transformation-related protein 53 (TP53) served as the core targets. The results of GOand KEGG enrichment analyses indicated that the alleviation of PE by HGD is mainly related to pathways including immuneresponse, regulation of gene expression, atherosclerosis, and tumorigenesis. Molecular docking results showed that the keyactive components in HGD could bind to the core targets spontaneously and stably. This study revealed that HGD may alleviatesymptoms in PE patients by regulating signaling pathways, modulating platelet function to exert anticoagulant effects, andregulating the expression of anti-inflammatory genes, which provided a direction for subsequent experimental research.展开更多
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
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
Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature....Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature.Through the integration of network biology,TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms,establishing a novel research paradigm for TCM modernization.The rapid advancement of machine learning,particularly revolutionary deep learning methods,has substantially enhanced artificial intelligence(AI)technology,offering significant potential to advance TCM network pharmacology research.This paper describes the methodology of TCM network pharmacology,encompassing ingredient identification,network construction,network analysis,and experimental validation.Furthermore,it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods.Finally,it addresses challenges and future directions regarding cell-cell communication(CCC)-based network construction,analysis,and validation,providing valuable insights for TCM network pharmacology.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
OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and ...OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.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 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
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
文摘To explore the material basis and mechanisms of the anti-inflammatory effects of Hibiscus mutabilis L..The active ingredients and potential targets of Hibiscus mutabilis L.were obtained through the literature review and SwissADME platform.Genes related to the inflammation were collected using Genecards and OMIM databases,and the intersection genes were submitted on STRING and DAVID websites.Then,the protein interaction network(PPI),gene ontology(GO)and pathway(KEGG)were analyzed.Cytoscape 3.7.2 software was used to construct the“Hibiscus mutabilis L.-active ingredient-target-inflammation”network diagram,and AutoDockTools-1.5.6 software was used for the molecular docking verification.The antiinflammatory effect of Hibiscus mutabilis L.active ingredient was verified by the RAW264.7 inflammatory cell model.The results showed that 11 active components and 94 potential targets,1029 inflammatory targets and 24 intersection targets were obtained from Hibiscus mutabilis L..The key anti-inflammatory active ingredients of Hibiscus mutabilis L.are quercetin,apigenin and luteolin.Its action pathway is mainly related to NF-κB,cancer pathway and TNF signaling pathway.Cell experiments showed that total flavonoids of Hibiscus mutabilis L.could effectively inhibit the expression of tumor necrosis factor(TNF-α),interleukin 8(IL-8)and epidermal growth factor receptor(EGFR)in LPS-induced RAW 264.7 inflammatory cells.It also downregulates the phosphorylation of human nuclear factor ĸB inhibitory protein α(IĸBα)and NF-κB p65 subunit protein(p65).Overall,the anti-inflammatory effect of Hibiscus mutabilis L.is related to many active components,many signal pathways and targets,which provides a theoretical basis for its further development and application.
基金supported by the Jilin Science and Technology Development Talent Special Project,Nos.20240601086RC,23JQ08(all to ZH)YDZJ202502CXJD077+1 种基金JLARS-2025-0802-09YDZJ202501ZYTS706.
文摘Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-related diseases like Alzheimer’s disease,osteoporosis,low immunity,glucose and lipid metabolism disorders,and cardiovascular diseases.With the continuous increase of the elderly population,the pressure on the medical industry is increasing.To lower the burden on the medical industry and increase the average age of the elderly,it is vital to explore effective anti-aging materials.Ginseng Radix et Rhizoma(Renshen),as a traditional and precious Chinese medicinal herb,is known as the“king of all herbs”.It is famous for its effects of“tonifying Qi,restoring pulse”(helping with the generation of Qi(the fundamental,vital energy that continuously flows within the body)and the circulation of blood)and strengthening the body,nourishing the spleen and lungs,generating fluids and nourishing blood,calming the mind and improving intelligence.Recently,its anti-aging effect has received increasing attention from modern scientific research.This study summarizes the pharmacological effects of the main active ingredients of Renshen(ginsenosides,polysaccharides,etc.)on resisting aging,including preventing neuroaging,suppressing skin aging,mitigating ovarian aging,inhibiting osteoporosis and arthritis,enhancing the immune system of the elderly,protecting the cardiovascular system,resisting aging-induced fatigue and exerting the anti-tumor effects.Through network pharmacology and molecular docking,the anti-aging active ingredients of Renshen were screened,and the key targets and pathways of anti-aging active ingredients in Renshen were determined.Using network pharmacology,totally 106 drug targets and 3,479 disease targets were screened,and 79 common targets between aging and Renshen were identified.Three core targets were identified in the PPI network,including TNF,AKT1,and IL-1β.Molecular docking was used to obtain further verification.This study emphasizes the potential of Renshen as a source of anti-aging activity,which can be developed into a novel drug for the treatment of age-related diseases.
基金supported by grants from the National Natural Science Foundation of China(82004252)the Project of Administration of Traditional Chinese Medicine of Guangdong Province(202405112017596500)the Basic and Applied Basic Research Foundation of Guangzhou Municipal Science and Technology Bureau(202102020533).
文摘Background:Wenqing Yin(WQY)is a classic prescription used to treat skin diseases like atopic dermatitis(AD)in China,and the aim of this study is to investigate the therapeutic effects and molecular mechanisms of WQY on AD.Methods:The DNFB-induced mouse models of AD were established to investigate the therapeutic effects of WQY on AD.The symptoms of AD in the ears and backs of the mice were assessed,while inflammatory factors in the ear were quantified using quantitative real-time-polymerase chain reaction(qRT-PCR),and the percentages of CD4^(+)and CD8^(+)cells in the spleen were analyzed through flow cytometry.The compounds in WQY were identified using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis and the key targets and pathways of WQY to treat AD were predicted by network pharmacology.Subsequently,the key genes were tested and verified by qRT-PCR,and the potential active components and target proteins were verified by molecular docking.Results:WQY relieved the AD symptoms and histopathological injuries in the ear and back skin of mice with AD.Meanwhile,WQY significantly reduced the levels of inflammatory factors IL-6 and IL-1βin ear tissue,as well as the ratio of CD4^(+)/CD8^(+)cells in spleen.Additionally,a total of 142 compounds were identified from the water extract of WQY by UPLC-Orbitrap-MS/MS.39 key targets related to AD were screened out by network pharmacology methods.The KEGG analysis indicated that the effects of WQY were primarily mediated through pathways associated with Toll-like receptor signaling and T cell receptor signaling.Moreover,the results of qRT-PCR demonstrated that WQY significantly reduced the mRNA expressions of IL-4,IL-10,GATA3 and FOXP3,and molecular docking simulation verified that the active components of WQY had excellent binding abilities with IL-4,IL-10,GATA3 and FOXP3 proteins.Conclusion:The present study demonstrated that WQY effectively relieved AD symptoms in mice,decreased the inflammatory factors levels,regulated the balance of CD4^(+)and CD8^(+)cells,and the mechanism may be associated with the suppression of Th2 and Treg cell immune responses.
基金supported by National Training Program of Innovation and Entrepreneurship for Undergraduates(202510163044).
文摘The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains to be elucidated.Employing a network pharmacology and molecular docking approach,this study systematically investigated the synergistic mechanism of the herb pair DC and LR in RA treatment.Active components and their corresponding targets were retrieved from the TCMSP database and relevant literature,and RA-related targets were collected from established disease databases.A total of 73 overlapping targets between DC-LR and RA were identified,among which core targets such as AKT1,TNF,and CASP3 were highlighted.GO and KEGG enrichment analyses revealed that these targets are involved in biological processes such as oxidative stress response and cell migration,and are significantly enriched in key pathways including HIF-1,TNF,and PI3K-Akt signaling pathways.Compatibility analysis further revealed that the combination of DC and LR may enhance therapeutic effects through synergistic regulation of shared targets and complementary modulation of upstream and downstream pathway components.Molecular docking confirmed strong binding affinities between core active components and key targets.This study provides a multi-dimensional“component-target-pathway”perspective on the potential synergistic anti-RA mechanism of the DC-LR herb pair,offering a theoretical basis for further experimental validation and clinical application.
基金supported by the National Natural Science Foundation of China(8197347182003937)。
文摘The gastroprotective activity of water extracts from Citrus reticulata'Chachi'leaves(JY)was investigated,and its potential action mechanisms were revealed using network pharmacology.First,the main chemical components of JY were identified using high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry,14 compounds were preliminarily identified,with flavonoids being the primary components.Next,the protective effect of JY on ethanol-induced damage was investigated in vitro.An MTT assay showed that JY could significantly promote the proliferation of GES-1 cells and reduce the damage caused by ethanol.A gastric ulcer model was induced in mice using ethanol,and JY(1,2,and 4 mg/kg)was orally administered to the mice to counteract ethanol-induced gastric ulcers.Pretreatment with JY reduced the severity of ethanol-induced gastric injury.Histopathological results showed that JY enhanced the cell structure of gastric tissue,increased the secretion of gastric mucosal mucus,and reduced gastric edema caused by ethanol injury.JY significantly decreased the levels of pro-inflammatory factors,including interleukin(IL)-1β,IL-6,and tumor necrosis factorα,in the serum.Additionally,JY increased the levels of prostaglandin E2 and the activity of total superoxide dismutase,while significantly reducing the levels of the lipid peroxidation product malondialdehyde in gastric tissue.In parallel,JY significantly upregulated the mRNA expressions of copper/zinc superoxide dismutase(Cu/Zn-SOD),manganese superoxide dismutase(Mn-SOD),and glutathione peroxidase(GPx)to alleviate oxidative stress.JY also promoted the healing of gastric ulcers by upregulating the mRNA expressions of vascular endothelial growth factor(VEGF)and epidermal growth factor receptor(EGFR).Finally,network pharmacology was used to analyze the potential bioactive substances in JY and their mechanisms.The results indicated that the protective effect of JY might be related to flavonoids and that JY exerts its gastroprotective effects by participating in the PI3K-Akt and VEGF signaling pathways.These findings suggest that JY could be a valuable natural resource for preventing ethanol-induced gastric injury.
基金supported by Research Project on Traditional Chinese Medicine in Heilongjiang Province in 2025(Research on the pharmacological substance basis of Huangqi Guizhi decoction in improving acute pulmonary embolism and lung injury based on the theory of“Diaphoresis and expanding meridian”No.ZHY2025-043).
文摘This study explored the therapeutic targets and molecular mechanisms of Huangqi Guizhi Decoction (HGD) in alleviatingpulmonary embolism (PE) by employing network pharmacology and molecular docking techniques. Firstly, the effective activecomponents of the Chinese herbs in HGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and their potential therapeutic targets were predicted using the Swiss Target Prediction platform. Subsequently, PErelatedtarget genes were obtained from the Online Mendelian Inheritance in Man (OMIM) database and GeneCards database.Then, the Wei Sheng Xin tool was used to generate a Venn diagram for identifying the common targets between the herb-relatedtargets and PE-related targets. After screening these common targets, a “drug-component-target network” and a protein-proteininteraction (PPI) network were constructed. Furthermore, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia ofGenes and Genomes (KEGG) enrichment analysis were conducted on the intersecting targets, and molecular docking verificationwas performed using AutoDockTools and PyMol software. Finally, 20 active components were screened from Astragali Radix, 7from Cinnamomi Ramulus, 13 from Paeoniae Radix Alba, 5 from Zingiberis Rhizoma Recens, and 29 from Jujubae Fructus, witha total of 983 therapeutic targets. Among these targets, 134 were associated with PE, and protein kinase B1 (AKT1), mitogenactivatedprotein kinase 1 (MAPK1), and transformation-related protein 53 (TP53) served as the core targets. The results of GOand KEGG enrichment analyses indicated that the alleviation of PE by HGD is mainly related to pathways including immuneresponse, regulation of gene expression, atherosclerosis, and tumorigenesis. Molecular docking results showed that the keyactive components in HGD could bind to the core targets spontaneously and stably. This study revealed that HGD may alleviatesymptoms in PE patients by regulating signaling pathways, modulating platelet function to exert anticoagulant effects, andregulating the expression of anti-inflammatory genes, which provided a direction for subsequent experimental research.
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 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.
基金supported by the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(No.2024C03106,X.F.)the National Natural Science Foundation of China(No.82474160,X.S.)+2 种基金the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LBZ24H270001,X.P.)the Major Joint Projects Supported by the National Administration of TCM and Zhejiang Province(No.GZY-ZI-KJ-23037,X.P.)the Ningbo Top Medical and Health Research Program(No.2022030309,X.P.)。
文摘Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature.Through the integration of network biology,TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms,establishing a novel research paradigm for TCM modernization.The rapid advancement of machine learning,particularly revolutionary deep learning methods,has substantially enhanced artificial intelligence(AI)technology,offering significant potential to advance TCM network pharmacology research.This paper describes the methodology of TCM network pharmacology,encompassing ingredient identification,network construction,network analysis,and experimental validation.Furthermore,it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods.Finally,it addresses challenges and future directions regarding cell-cell communication(CCC)-based network construction,analysis,and validation,providing valuable insights for TCM network pharmacology.
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.
基金Shanghai Clinical Research Center for Chronic Musculoskeletal Diseases (20MC1920600)Shanghai Key Clinical Specialty "Traditional Chinese Medicine Orthopaedic Traumatology"(shslczdzk03901)+3 种基金The Second Round of Construction Project of National TCM Academic School Inheritance Studio "Shi's Trauma Department"[Letter of the People's Education of Traditional Chinese Medicine (2019) No.62]Shanghai High-level Local Universities "Chronic Muscle and Bone Damage Research and Transformation" Innovation Team [No.3 of Shanghai Education Commission (2022)]Program for Shanghai High-Level Local University Innovation Team (SZY20220315)Shanghai Shenkang Hospital Development Center Clinical Three-year Action Plan (SHDC2020CR3090B)。
文摘OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.
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.
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.
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.
