Exploring the mechanism of action of Danggui Shaoyao San in the treatment of polycystic ovary syndrome based on integrated pharmacology and molecular docking

Background:We used integrated pharmacology and molecular docking to investigate the mechanism of action of Danggui Shaoyao San(DSS)in the treatment of polycystic ovary syndrome(PCOS),and to provide a basis for subsequent systematic studies.Methods:The Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP)V2.0 was used for target prediction of the drugs within DSS.Relevant targets for PCOS were retrieved in the human gene database(GeneCards)and imported within TCMIP V2.0.Relying on the“Chinese medicine association network mining”module in the TCMIP V2.0 platform,the“drug target-disease target”interaction network is constructed.We continue to enrich and analyze the potential targets of the above drugs for disease intervention through the TCMIP V2.0 platform,draw a multidimensional network map of“Chinese herbal medicine–chemical composition–disease–potential target–pathway”and validate the intersection of chemical composition and drug with disease by molecular docking.Results:There are 88 potential targets and 28 potential core targets among the action targets of DSS and PCOS.Combined with protein-protein interaction network analysis,the potential core targets of disease and drug intersection are estrogen receptor 1 androgen receptor.The binding energies obtained by molecular docking were all≤-5.0 kJ/moL,indicating that the potentially active chemical components have good binding activity to the intersection targets.Conclusion:DSS has the potential to be a multi-target and multi-pathway treatment for PCOS.

Effects of acupuncture on Alzheimer’s disease: the mechanistic study

Introduction Alzheimer’s disease(AD)is a degenerative disease of the central nervous system characterized by memory loss and cognitive impairment,often accompanied by emotional apathy,agitation,depression,delusions aggression,and other psychological symptoms[1–3].Psychological symptoms such as apathy,agitation,and depression tend to increase with the duration and severity of AD.

Study on hepatotoxicity of Aconitum brachypodum based on network pharmacology and molecular docking

Objective:To explore the potential mechanism of hepatotoxicity induced by Aconitum brachypodum through network toxicology.Methods:The active components and targets of Aconitum brachypodum were identified and screened by CNKI,PubChem database,Swiss Target Prediction database.Genecards,pharmGKB and DisGeNET databases were used to collect hepatotoxicity related targets.The intersection targets were obtained by matching the active component targets with the hepatotoxic targets of Aconitum brachypodum.Cytoscape software was used to construct the"Aconitum brachypodum-potential active components-potential targets-hepatotoxicity"network.The STRING database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software.The toxic components in Aconitum brachypodum were docked with the core targets.Results:In this study,26 chemical components were screened via SwissADME,297 targets for the active components of Aconitum brachypodum were obtained.There were 1,096 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Aconitum brachypodum,and 15 potential active components,among which Penduline,Songoramine,Sitosterol,Daucosterol and Bullatine A were the key active components for hepatotoxicity caused by Aconitum brachypodum,and signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),mitogen-activated protein kinase 8(MAPK8)and tyrosine-protein kinase JAK2(JAK2)were the potential targets for hepatotoxicity caused by Aconitum brachypodum.There were 1,133 GO entries(P<0.05),including 1,045 entries of biological process(BP),19 entries of cellular component(CC),and 69 entries of molecular function(MF).KEGG enrichment analysis revealed 115 pathways(P<0.05),of which EGFR tyrosine kinase inhibitor resistance,hypoxia-inducible factor 1(HIF-1)signaling pathway,PI3K-Akt signaling pathway,calcium signaling pathway,T helper 17(Th17)cell differentiation was strongly correlated with the hepatotoxicity caused by Aconitum brachypodum.Molecular docking results showed that the binding activity was good.Conclusion:Through network toxicology analysis,it was found that the active ingredients in Aconitum brachypodum may act on multiple targets and signaling pathways,thereby participating in the activation of an excessive inflammatory response,oxidative stress,apoptosis and other pathways on the whole,thus resulting in hepatotoxicity.

Molecular mechanism of Herba Eupatorii in treating COVID-19 based on network pharmacology and molecular docking

Objective:To explore the therapeutic target and molecular mechanism of Herba Eupatorii in the intervention of COVID-19(coronavirus disease 2019)by network pharmacology.Methods:TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)and TCMIP V2.0(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine)databases were used to search the active ingredients and corresponding drug targets of Herba Eupatorii.Related targets of COVID-19 were searched in Genecards,pharmGKB,CTD,Drugbank and TTD databases.After the intersection targets were selected using VENNY 2.1 online platform,the PPI(protein-protein interaction)network was downloaded into STRING database,and the data were analyzed and sorted out using Cytoscape software to obtain the potential key targets for the treatment of COVID-19 by Herba Eupatorii.At the same time,using the data of active ingredients and intersection targets,a network of"TCM-active ingredients-key targets"was constructed in Cytoscape software to screen out chemical molecules with potential therapeutic effects.GO(Gene Ontology)functional enrichment analysis and KEGG(Kyoto Encyclopedia of Genes)pathway enrichment analysis of key target proteins were performed by R software.AutoDock Vina program was used for molecular docking of the top 5 active ingredients and key targets to calculate the minimum binding energy.Results:There were 26 active ingredients,160 targets,and 1969 pathogenic genes of COVID-19,among which 59 genes were intersection targets of drugs and diseases.After PPI network screening,the key target proteins were AKT1(RAC-alpha serine/threonine-protein kinase),JUN(transcription factor AP-1),TP53(cellular tumor antigen p53),ACTB(actin beta)and EGFR(epidermal growth factor receptor).Through the network of"TCM-Active Ingredients-Key Targets",Luteolin,Eupatolin,Stigmasterol,Eupatoriopicrin and Dammaradienyl acetate were identified as the active ingredients with potential therapeutic effects in the treatment of COVID-19.After R software was used for GO enrichment analysis,1978 GO items were obtained(P<0.05),including 1870 BP items,26 CC items and 82 MF items.149 pathways were obtained by KEGG enrichment analysis(P<0.05).It mainly involves IL-17(interleukin-17)signaling pathway,TNF(tumor necrosis factor)signaling pathway,C-type lectin receptor signaling pathway,PI3K-Akt(phosphatidylinositol 3 kinase-protein kinase B)signaling pathway,and T Cell receptor signaling pathway,etc.The molecular docking results showed that the active ingredients had good binding activity with key targets.Conclusion:Through the potential chemical constituents of Luteolin,Eupatolin,Stigmasterol,Eupatoriopicrin and Dammaradienyl acetate,Herba Eupatorii may act on AKT1,JUN,TP53,ACTB,EGFR and other targets.Involvement in IL-17 signaling pathway,TNF signaling pathway,C-Type Lectin receptor signaling pathway,PI3K-Akt signaling pathway,T Cell receptor signaling pathway and other pathways play an anti-inflammatory and antiviral roles in intervening in the occurrence and development of COVID-19.

Study of the potential mechanism of acupuncture treatment for functional dyspepsia based on association rule mining and bioinformatics/network pharmacology approach

Objective:To explore the main acupoint prescription and mechanism of acupuncture in treating Functional dyspepsia(FD)by analyzing the clinical randomized controlled trial literature on acupoints and targets of acupuncture in the treatment of FD combined with association rule mining and bioinformatics/network pharmacology methods.Methods:Search relevant clinical randomized controlled trial literature on acupoints and therapeutic targets of acupuncture in the treatment of FD from eight databases from their inception to June 18th,2022.We obtained acupuncture selection points,meridian,and therapeutic targets and established acupoints database for acupuncture treatment of FD.FD-related targets were collected from GeneCards,DisGeNET,OMIM,and DrugBank databases.We obtained the potential targets of acupuncture on FD by taking the intersection of acupuncture for FD therapeutic targets and FD-related targets.We performed the protein-protein interaction network,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results:In this study,26 Randomized Controlled Trials related to acupuncture treatment of FD were retrieved.We obtained 29 acupoints,17 acupuncture for FD therapeutic targets,and 10 intersection targets.Tumor necrosis factor(TNF),Interleukin(IL)-1,and Neuropeptide Y(NPY)are key targets of acupuncture in the treatment of FD.Conclusion:ST36-CV12-PC6-LR3 is the main acupoint prescription for FD.Acupuncture may affect Neuroactive ligand-receptor interaction,Gastric acid secretion,and IL-17,TNF signaling pathways by regulating related key targets,and play a synergistic role in the treatment of FD by inhibiting gastric acid secretion,alleviating inflammatory response,regulating the brain-gut axis,improving mood and other aspects.

The mechanism of hepatotoxicity of Nux Vomica:a network-pharmacology-based study

Objective:To explore the potential mechanism of hepatotoxicity induced by Nux Vomica through network toxicology.Methods:The active components and targets of Nux Vomica were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database(TCMSP),literature research,PubChem Database,Swiss Target Prediction database,etc.Genecards,pharmGKB and OMIM databases were used to collect hepatotoxicity related targets,then,cross them with active component targets to obtain potential targets of hepatotoxicity caused by Nux Vomica.A"Nux Vomica-Potential active components-Potential targets-Hepatotoxicity"network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software,and then the obtained pathways directly related to hepatotoxicity were integrated.Results:In this study,37 active components were screened via TCMSP and literature research,468 targets for the active components of Nux Vomica were obtained.There were 533 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Nux Vomica,and 26 potential active components,among which Ferulic acid,Novacine,Icajine,Simiarenol were the key active components for hepatotoxicity caused by Nux Vomica,and JUN,RELA,and STAT3 were the core target proteins of hepatotoxicity caused by Nux Vomica.There were 1859 GO entries(P-value<0.05),including 1709 entries of Biological Process(BP),39 entries of Cellular Component(CC),and 111 entries of Molecular Function(MF).KEGG enrichment analysis revealed 145 pathways(value<0.05),of which PI3K/AKT signaling pathway,HIF-1 signaling pathway,EGFR tyrosine kinase inhibitor resistance were strongly correlated with the hepatotoxicity caused by Nux Vomica.Conclusion:Through network toxicology analysis,it was found that lots of potential components in Nux Vomica may be involved in the activation of the excessive inflammatory response,oxidative stress,and the LPS response through multiple targets and multiple pathways,resulting in the generation of hepatotoxicity.

Progress in the effect of inflammatory microenvironment on osteoarthritis

Osteoarthritis(OA)is the most common chronic joint degenerative disease in the population,involving progressive focal cartilage degeneration,bone hypertrophy(osteophyte formation and subchondral osteosclerosis),synovial joint inflammation,synovial sac thickening,and structural changes of periarticular ligaments and peripheral muscles[1],among which the degeneration of articular cartilage and joint inflammation are the main characteristics[2].

To explore acupuncture therapy for post-stroke gastrointestinal dysfunction based on gut microbiota

The occurrence of post-stroke gastrointestinal disorder(PSGD)is closely related to gut microbiota.Acupuncture has a positive effect on PSGD.However,it is not completely clear how acupuncture can mediate the regulation of gut microbiota in the treatment of PSGD.In this paper,the relationship between PSGD risk factors and gut microbiota,the relationship between gut microbiota and PSGD,the regulation of gut microbiota and metabolites by acupuncture,and the application research progress of acupuncture in regulating PSGD were reviewed to explore the mechanism of gut microbiota in the treatment of PSGD.We found that acupuncture can improve intestinal mucosal permeability,increase the number of beneficial bacteria such as Bifidobacterium and Lactobacillus,and increase serum 5-hydroxytryptamine(5-HT)and short chain fatty acids(SCFAs)to relieve gastrointestinal symptoms and improve PSGD.