Effects of ginkgo flavone aglycone on atherosclerosis based on network pharmacology,molecular docking,and in vitro experiments

Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.

Exploring the molecular mechanism of Suoquan pill in the treatment of diabetic kidney disease based on network pharmacology,molecular docking,in vitro experiment

Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.

The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug development.However,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted therapies.Furthermore,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

Exploring the mechanism of icariin in regulat⁃ing cardiac microvascular endothelial cells based on network pharmacology,molecular docking and in vitro experiments

OBJECTIVE To investigate the regulatory effects of icariin(ICA)on cardiac micro⁃vascular endothelial cells(CMEC)after oxygenglucose deprivation reperfusion(OGD/R)injury.METHODS CMEC were subjected to OGD/R treatment to construct a myocardial ischemiareperfusion model,and were divided into normal,model,low(10μmol·L^(-1)),medium(20μmol·L^(-1))and high(40μmol·L^(-1))ICA group,and high ICA+inhibitor group(40μmol·L^(-1)+20 nmol·L^(-1)).CCK-8 assay was used to assess the protective ability of ICA against CMEC,and cell migration assay and tube-formation assay were used to detect the migration and generation ability of CMEC.The TCMSP database,Swiss-Target database and literature mining methods were used to col⁃lect ICA-related targets,the GeneCards data⁃base was used to collect target genes related to myocardial ischemia/reperfusion,and Cytoscape 3.8.0 software was used to construct a"drug-tar⁃get-disease"network.The potential targets were imported into STRING 11.5 database to obtain the PPI network.GO and KEGG enrichment analyses were performed on the potential targets using the DAVID database.Molecular docking was performed using AutoDock-vina 1.1.2 soft⁃ware.Western blot detected the expression of related proteins.RESULTS After CMEC was subjected to OGD/R treatment,ICA had a protec⁃tive effect at 10^(-1)60μmol·L^(-1);the results of the cell migration assay showed that each group of ICA could promote the migratory effect of CMEC(P<0.01,P<0.01);and the results of tube-for⁃mation assay showed that each group of ICA could significantly promote the generation of branches(P<0.01)and the capillary length exten⁃sion(P<0.05).Network pharmacology collected a total of 23 ICA action targets,1500 disease tar⁃gets and 12 key targets.GO function enrichment analysis found 85 results.KEGG pathway enrich⁃ment analysis found 53 results,involving AGERAGE signaling pathway,sphingolipid signaling pathway and VEGF signaling pathway.Molecu⁃lar docking results showed that ICA had better binding with core targets PRKCB,PRKCA and PTGS2.Western blot results showed that ICA could regulate the expression of PRKCB,PRKCA and PTGS2 proteins.The results of cell migra⁃tion assay,tube-formation assay and protein expression were reversed after addition of PKC inhibitor.CONCLUSION The potential mecha⁃nism of action of ICA against myocardial isch⁃emia-reperfusion injury may be related to the reg⁃ulation of processes such as CMEC migration and angiogenesis,and it functions through the key target gene PKC.

Molecular Mechanism of Ginseng in Treating Nephrotic Syndrome Based on Network Pharmacology and Experimental Verification

[Objectives]To study the potential molecular mechanism of ginseng in treating nephrotic syndrome(NS)by using network pharmacology,molecular docking and experimental verification methods.[Methods]The active components and targets of ginseng were obtained through the network pharmacology database,and the potential targets for the treatment of NS were predicted.The STRING data platform and Cytoscape software were used to construct protein interaction network,and carry out GO and KEGG enrichment analysis.Molecular docking of active components of ginseng and core targets was performed.The in vitro experiment verified the improvement effect of kaempferol,a key active ingredient of ginseng,on podocyte injury.[Results]After screening,17 active components of ginseng and 38 key targets for treating NS were obtained.GO and KEGG enrichment analysis showed that NF-κB,MAPK and other inflammatory pathways were involved.Molecular docking results show that the core components had good binding activity to key targets.The results of in vitro experiments show that kaempferol can reduce the phosphorylation level of AKT1,down-regulate the expression levels of NF-κB p65 and p-NF-κB p65,play an anti-inflammatory effect by inhibiting the activation of NF-κB pathway,and improve podocyte injury.[Conclusions]Ginseng may play a role in the treatment of NS by regulating multiple targets and pathways such as inflammatory response,substance metabolism,and signal transduction.

Exploring the mechanism of action of DHI on myeloproliferative neoplasms based on network pharmacology

Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and relevant literature were used to search for the active ingredients and targets of Radix Salviae and Carthami Flos in DHI.Disease targets related to myeloproliferative neoplasms were obtained from the GEO database,GeneCards,and DisGeNET database.The queried component targets were normalized using the UniProt database.Potential targets were identified by constructing protein-protein interactions networks using STRING 11.5 and visualized and analyzed using Cytoscape 3.9.1.GO and KEGG analysis were performed using the Metascape platform,and visualization was done using the built-in plug-in CluoGO or SangerBox platforms with Cytoscape 3.9.1.Results:The active ingredients of DHI for treating myeloproliferative neoplasms mainly consist of flavonoids and o-benzoquinones,including quercetin,luteolin,kaempferol,stigmasterol,tanshinone iia,cryptotanshinone,beta-carotene,2-isopropyl-8-methylphenanthrene-3,4-dione,and neocryptotanshinone ii.The potential targets are JUN,TP53,STAT3,AKT1,MAPK1,RELA,TNF,MAPK14,IL6,and FOS.The relevant signaling pathways involved are mainly TNFαsignaling pathway,PI3K-Akt signaling pathway,apoptosis,IL-17 signaling pathway,cellular senescence,MAPK signaling pathway,p53 signaling pathway,JAK-STAT signaling pathway,and NF-kappa B signaling.Conclusions:DHI acts mainly through flavonoids and o-benzoquinones to treat myeloproliferative neoplasms in a multi-targeted and multi-pathway manner.

Plant profile,phytochemistry and pharmacology of Cordia dichotoma(Indian cherry):A review

More than half of the world's population relies on the traditional medicine and major role of the traditional medicine including the use of plant extract and their active constituents.Among them,Cordia dichotoma Forst.,a small to moderate size plant of family Boragenaceae.commonly called bhokar,lasura,gonda,Indian cherry and shlesmataka.Plant parts such as leaves,fruit,bark and seed have been reported for possessing antidiabetic,antiulcer,anti-inflammatory,immune-modulator and analgesic activity.Screening of fruit,leaves and seed shows the presence of pyrrolizidine alkaloids,coumarins,flavonoids,saponins,lerpenes and sterols.Present review focuses on details of geographical distribution,physicochemical parameters,phytoconstituents and pharmacological properties of Cordia dichotoma reported so far.

Systems pharmacology for traditional Chinese medicine with application to cardio-cerebrovascular diseases

Identified as a treasure of natural herbal products,traditional Chinese medicine(TCM)has attracted extensive attention for their moderate treatment effect and lower side effect.Cardio-cerebrovascular diseases(CCVD)are a leading cause of death.TCM is used in China to prevent and treat CCVD.However,the complexity of TCM poses challenges in understanding the mechanisms of herbs at a systems-level,thus hampering the modernization and globalization of TCM.A novel model,termed traditional Chinese medicine systems pharmacology(TCMSP)analysis platform,which relies on the theory of systems pharmacology and integrates absorption,distribution,metabolism,excretion and toxicity(ADME/T)evaluation,target prediction and network/pathway analysis,was proposed to address these problems.Here,we review the development of systems pharmacology,the TCMSP approach and its applications in the investigations of CCVD and compare it with other methods.TCMSP assists in uncovering the mechanisms of action of herbal formulas used in treating CCVD.It can also be applied in ascertaining the different syndrome patterns of coronary artery disease,decoding the multi-scale mechanisms of herbs,and in understanding the mechanisms of herbal synergism.

Research advances in phytochemistry,pharmacology and toxicology of oleanolic acid

Oleanolic acid(OA)is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1.OA is widespread in traditional Chinese herbal medicine(Ligustri Lucidi Fructus,Achyranthis Bidentate Radix,Red Sage)and berries(blueberries,grapes).In recent years,because of the extensive pharmacological effects of OA,its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers.OA has effective therapeutic effects on a series of chronic diseases such as inflammation,cancer,diabetes,and cardiovascular diseases through multiple signaling pathways and various targets.Especially in cancers,such as colorectal cancer,liver cancer,gastric cancer,lung cancer,breast cancer and other malignancies,OA presents substantial efficacy.However,its poor aqueous solubility,needy bioavailability,and unsatisfactory pharmacological activity excessively restrict its clinical application.More importantly,the improper utilization of OA can cause adverse reactions,toxic effects and even damage to organs in some specific situations.With the discovery of various pharmacological effects,the complex action mechanisms of OA,the continuous progress in structural modification of OA,as well as the synthesis of OA derivatives,its application is expanding gradually.Among numerous studies,there is a clear indication that OA and its derivatives,if fully developed,may provide an alternative and cheaper treatment for a variety of chronic diseases.However,the specific molecular mechanisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer,diabetes,cardiovascular disease and other chronic diseases remain to be clarified.Therefore,it is necessary to further study the pharmacokinetics,pharmacological activity,specific targets and related mechanisms of OA to lay a solid foundation for drug development and the application of OA in clinical settings.

Anti-tumor pharmacology of natural products targeting mitosis

Cancer has been an insurmountable problem in the history of medical science.The uncontrollable proliferation of cancer cells is one of cancers main characteristics,which is closely associated with abn ormal mitosis.Targeting mitosis is an effective method for cancer treatment.This review summarizes several natural products with anti-tumor effects related to mitosis,focusing on targeting microtubulin,inducing DNA damage,and modulating mitosis-associated kinases.Furthermore,the main disadvantages of several typical compounds,including drug resistance,toxicity to non-tumor tissues,and poor aqueous solubility and pharmacokinetic properties,are also discussed,together with strategies to address them.Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.

Botany,Traditional Uses,and Pharmacology of Polygonati Rhizoma

Huang Jing (黄精 Polygonati Rhizoma, PR) was first documented as a herbal medicine in Ming Yi Bie Lu (《名医别录》 Miscellaneous Records of Famous Physicians) in China. However, there was no comprehensive review on the botany, traditional uses, and pharmacological effects of PR till now. In this study, the botany, traditional uses including Taoist medicine, and pharmacological effects of PR were reviewed and summarized to provide insights on drug development of PR. In Taoist medicine, PR maintains agerasia and helps prolong human life-span, and is used for fasting (Bigu). In the Zhong Guo Yao Dian (《中国药典》Chinese Pharmacopeia) version 2020, PR exerts replenishing qi and nourishing yin, invigorating the spleen, moistening the lung, and strengthening the kidney. Pharmacological studies show that PR has effects of anti-oxidation, anti-diabetes, anti-osteoporosis, anti-cancer, anti-hyperlipidemia, cardiomyocyte protection, immunomodulatory, and thus can be used for treatment of infertility, anti-microorganisms, and improving sleep and memory. In conclusion, PR may play a potential role for chronic disease management and health preservation and this very role deserves a more in-depth research.

Pulsatilla chinensis:phytochemistry,pharmacology and new drug development

Pulsatilla chinensis is a widely used traditional Chinese herb,which contains 56 types of chemical constituents,mainly including triterpenoid saponins,organic acids,coumarins and lignans.The largest portion of the ingredients in Pulsatilla chinensis is the family of triterpenoid saponins,in which anemoside B4 is the major effective compound and indexing component.The main components of Pulsatilla chinensis can metabolize into a vast array of active products in vivo,which play vital roles in its biological activity.Mounting evidence reveals that Pulsatilla chinensis exerts a wide range of therapeutic activities,such as anti-cancer,immunoregulation,anti-inflammation and anti-schistosome,with fewer adverse reactions,via various signaling pathways and multiple targets.It was documented that the active ingredient of Pulsatilla chinensis can lessen the drug resistance and synergize the effects of other natural products including paclitaxel,as well as ameliorate the clinical efficacy of chemical drugs,such as adriamycin.However,Pulsatilla chinensis was also reported to be possibly the main cause of hemolysis and chronic liver injury.The efforts should be made to deeply investigate the pharmacological actions and underlying mechanisms of Pulsatilla chinensis,with a focus on the anti-cancer efficacy,and develop new drugs based on the components of Pulsatilla chinensis for future utilization in the clinical setting.

Application of Intravenous Indwelling Needle in Undergraduate's Pharmacology Teaching Experiment

In this study,an intravenous indwelling needle was placed in the central artery of rabbit ear for collecting blood.The results show that this method greatly improves the success rate of blood sampling and well controls the experimental time.The students'unanimous feedback was that the method is simple and easy to operate,which is of great help to the stability of the experimental results.

Study on potential mechanism of hyperoside on improving ischemia/reperfusion injury based on network pharmacology

OBJECTIVE To predict the potential targets of hyperoside(Hyp)on improving ischemia/reperfusion injury by network pharmacology,and explore its possible mechanism combined with related literature.METHODS The action targets of Hyp and ischemia/reperfusion injury were obtained by TCMSP,Swiss Target Prediction,Pharm Mapper,Similarity ensemble approach,Online Mendelian Inheritance in Man,DisGENT and database.The common targets of drugs and diseases were screened by Omishare and STRING database respectively,and the protein-protein interaction(PPI)network map was constructed.Then the interaction network between Hyp and disease targets was constructed by Cytoscape software and topological cross-linking analysis was carried out.Then the interaction network between Hyp and disease targets was constructed and cross-linked analysis was carried out by using Cytoscape software.The gene ontology(GO)of the core target was analyzed by David database,and then the related pathways of the core target were enriched by KEGG database.RESULTS A total of 54 GO enrichment processes were obtained by GO enrichment analysis of 44 common genes,including 38 biological processes(BP),15 cell composition(CC)processes,and 1 molecular functional(MF)process.43 items were obtained by signal pathway enrichment analysis in KEGG database.CONCLUSION It is suggested that the mechanism of Hyp may be related to PI3K-Akt,RAP1,RAS,VEGF and other signal transduction pathways.The above results laid a theoretical foundation for the study of the mechanism and clinical application of the treatment of ischemia/reperfusion injury.

Opinion on pharmacology research and new drug development from precision medicine

Since President Obama announced the Precision Medicine Initiative from a national strategy perspective in his State of the Union address,precision medicine has rapidly become a world-wide hotspot and drawn global attention in the medical field.Precision medicine aims at applying genetic information of individual diseases to guide his or her diagnosis and treatment.

Mechanism of Ginkgo biloba L.leaf in the treatment of ischemic stroke based on network pharmacology,bioinformatics and molecular docking

Ginkgo biloba L.leaf(GBL)has been reported to protect against ischemic stroke(IS),one of the leading causes of death and longterm disability worldwide,while there is a lack of systematic study on the exact mechanism.Here,network pharmacology and bioinformatics were used to predict the active components,important targets,and potential mechanisms of GBL in the treatment of IS.Active compounds of GBL were screened based on drug-like index and oral bioavailability,key target genes were screened based on network pharmacology and gene chip,downstream pathways for the regulation of key target genes were predicted based on gene set enrichment analysis,and the interaction between key targets and active compounds was verified based on molecular docking.The results showed that GBL played a protective role in cerebral ischemia with mainly 14 active compounds,such as isoquercitrin,luteolin-4’-glucoside,beta-sitosterol,campesterol,diosmetin,ginkgolide B,ginkgolide C,ginkgolide J,ginkgolide M,isogoycyrol,laricitrin,luteolin,sesamin,and stigmasterol.Further studies revealed that GBL played important role in immunomodulation and inflammation inhibition after cerebral ischemia by acting on its peripheral targets ARG1 and MMP9 to regulate Toll-like receptor,Chemokine and Notch signaling pathway.Meanwhile,GBL played important role in reducing neuroinflammation and blood-brain barrier damage after cerebral ischemia by acting on its central targets,CCL2,PTGS2,IL6,IL1B and MMP9 to regulate the Cytokine-cytokine receptor interaction,Jak-STAT,and Toll-like receptor signaling pathway.Additionally,molecular docking verified that the active compounds mentioned above could bind to ARG1,MMP9,CCL2,PTGS2,IL6,and IL1B.The present study shows the multicomponent,multitarget and multichannel pharmacological effects of GBL on cerebral ischemia and provides a new strategy for the treatment of IS.

A network pharmacology approach combined with animal experiment to investigate the blood enriching effect of Gei herba

Background:To explore active components of Lanbuzheng(Gei herba)and its underlying complex mechanism in treating blood deficiency induced by chemotherapy drug based on network pharmacology and mice experimental validation.Methods:Active components of Lanbuzheng(Gei herba)were screened by Lipinski’s rule of five.Targets acted with active components were predicted by PharmMapper database,and targets whose function associated with blood deficiency were screened by Therapeutic Target Database and UniProt.The networks of component-target and target-pathway were constructed by Cytoscape.The levels of peripheral blood and organ indexes were detected in the animal experiments.Results:One hundred and seventy-three components of Lanbuzheng(Gei herba)were collected,and 60 active components were screened according to the rule of five.According to the degree value of compounds,the top 5 compounds were docosyl trans ferulate,C32 decursin,agrimonolide 6-O-β-D-glucoside,degree=11,173-ethoxyphaeophorbide,and eugenol.Finally,59 targets associated with blood deficiency were obtained and the top 5 targets were MAPK14,TTR,CDK2,AKR1B1 and AR.Based on the interaction network of componenttarget and target-pathway,it’s found that 60 active components could act with 59 targets and 44 pathways for treating blood deficiency.And then,the mice experiments showed that Lanbuzheng(Gei herba)could enrich blood by increasing the levels of red blood cell,white blood cell,hemoglobin,red blood cell specific volume and platelet,and the indexes of liver,thymus and spleen,which validated the treating effect of Lanbuzheng(Gei herba).Conclusion:In this study,a network pharmacology approach and animal experiments were established to explore the nourishing blood effect of Lanbuzheng(Gei herba).The results demonstrated that Lanbuzheng(Gei herba)could improve blood deficiency and provide a theoretical basis for the further research on the in-depth mechanism of Lanbuzheng(Gei herba).

Prediction of the mechanisms of liver injury of Epimedii Folium by network pharmacology and validation in HepaRG Cells

Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.

Network pharmacology prediction and molecular docking-based strategy to investigate the possibility of CPL against myeloproliferative neoplasms

Background:Compound cortex phellodendri liquid(CPL)is a kind of classical compound preparation,which has potential curative effect in treating inflammatory diseases.Increasing evidences support that inflammation plays important roles in the pathogenesis of myeloproliferative neoplasms(MPN).This study aims to preliminarily clarify the therapeutic potential and molecular mechanisms of CPL for MPN based on network pharmacology and molecular docking techniques.Methods:The active components and corresponding action targets of CPL were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),while MPN-related targets were searched through GeneCards,DisGeNET,OMIM,DrugBank and TTD databases respectively.Protein-Protein Interaction(PPI)Networks of potential targets were constructed using STRING 11.5 and analyzed visually with Cytoscape 3.9.1.In addition,Metascape platform was used for GO and KEGG analysis that were subsequently visualized with Cytoscape 3.9.1 built-in plug-ins CluoGO or SangerBox platform.Finally,Autodock Vina was used for molecular docking of potential targets and main active ingredients,which were visualized with Pymol software.Experimentally,we used in vitro mouse primary cells culture system to evaluate the effect of CPL on the erythroid and megakaryocytes differentiation that are excessively driven in MPN respectively.Results:The active components of CPL in the treatment of MPN are mainly flavonoids.The core proteins of CPL for MPN intervention are correlated to TP53,AKT1,JUN,CASP3,EGFR,TNF,MYC,IL6.Multiple signaling pathways were closely related to the treatment of MPN intervened by CPL,including PI3K-Akt signaling,TNF-αsignaling,JAK-STAT signaling and NF-κB signaling pathways.These potential targets had good conformation with the core active ingredients of CPL.In line with above findings,we demonstrated that CPL significantly inhibits the proliferation of differentiation of erythrocytes and megakaryocytes in vitro,further supporting the therapeutic potential of CPL for MPN.Conclusion:This study revealed the active ingredients and potential molecular mechanism of CPL in the treatment of MPN,providing a reference for subsequent basic research.

Analysis of the action mechanism of Fang Ji Huang Qi decoction in treating rheumatoid arthritis by network pharmacology

目的:通过网络药理学探讨防己黄芪汤治疗类风湿性关节炎的药理学机制.方法:通过中药系统药理学分析平台(TCMSP)检索中药的化学成分和作用靶点,并于UniProtKB网络平台获取每种靶蛋白的基因名.通过CTD数据库查询类风湿性关节炎的疾病靶点.在STRING数据库中构建蛋白-蛋白相互作用网络(PPI),在Cytoscape中进行网络可视化分析.通过DAVID数据平台对关键靶蛋白进行基因本体论(GO)分析,京都基因与基因组百科全书(KEGG)富集通路分析.结果:从TCMSP数据库中共筛选得到472个药物有效成分,从CTD数据库中筛选出75个疾病靶点.化合物-靶点网络图中包含98个进一步筛选出的药物有效成分和相应的75个靶点,关键化合物有槲皮素、山柰酚等,关键靶点为PTGS2和NOS2等.PPI网络包括75个蛋白,关键蛋白为37个,涉及TP53,JUN,IL6等.GO条目260个,生物功能条目最多,共246个.KEGG通路共55条,主要涉及肿瘤信号通路,Toll样受体信号通路,NOD样受体信号通路.结论:本研究结果初步验证了防己黄芪汤治疗类风湿性关节炎的基本药理作用及其机制,并为进一步深入揭示其作用机制奠定了良好基础.