Network pharmacology

摘要： Background:The Jiawei Yangshen pill enhances sperm abundance.However,the pharmacological mechanism of action of the Jiawei Yangshen pill remains unclear.This study aimed to explore the therapeutic effect of the Jiawei Yangshen pill in the treatment of dyszoospermia and study the underlying mechanism.Methods:A dyszoospermia model was established by injecting mice with cyclophosphamide(50 mg/kg)consecutively for 7 days.Physiological and pathological indicators of the testis and hormone levels were examined after 4 weeks of treatment.Untargeted metabolomics using high-performance liquid chromatograph-mass spectrometry was performed on testis specimens.Network pharmacology analysis was used to construct an“ingredient-target-disease”interactive network,followed by metabolic pathway enrichment analysis.Western blotting was performed to examine the levels of the related proteins.Results:The Jiawei Yangshen pill significantly increased the testis index,epididymal index,sperm count,and testosterone level,while concurrently decreasing sperm mortality and luteinizing hormone levels.The spermatogenic cells in the Jiawei Yangshen pill-treated mice were well arranged with an increased number.Significantly different metabolites were identified.Western blotting showed that the expression levels of p-anti-adenosine monophosphate-activated protein kinase/anti-adenosine monophosphate-activated protein kinase and p-protein kinase B/protein kinase B were significantly increased after the Jiawei Yangshen pill treatment,whereas the expression levels of transforming growth factor-β1 and nuclear factor kappa B(p65)were remarkably decreased.Conclusion:The Jiawei Yangshen pill significantly improved testicular microcirculatory injury and overall metabolic levels in mice with dyszoospermia.

摘要： Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compounds based on network pharmacology.Methods:Using network pharmacology,a"traditional Chinese medicine-chemical composition-key target-pathway"analysis was conducted on Radix Paeoniae Alba for the treatment of Toosendan Fructus-induced hepatotoxicity.The possible mechanism of action was analyzed in terms of function.Results:The core targets,such as interleukin(IL)-6,tumor necrosis factor(TNF),heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator-activated receptor gamma(PPARG),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),Jun proto-oncogene(JUN),caspase-3,estrogen receptor 1(ESR1),and aryl hydrocarbon receptor(AHR)were screened from the targets of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity.Biological process(BP)of toxic targets(BP terms)involved"response to drug;activation of cysteine-type endopeptidase activity involved in apoptotic process,”positive regulation of transcription.Cellular components(CC terms)mainly involved cytosol and membrane rafts.Molecular function(MF)terms included"protein homodimerization activity,"RNA polymerase II transcription factor activity and enzyme binding,etc."The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway included the TNF signaling pathway,cancer pathways,and apoptosis.Conclusion:Radix Paeoniae Alba might alleviate Toosendan Fructus-induced hepatotoxicity through IL6,TNF,HSP90AA1,PPARG,PTGS2,HMOX1,and other targets,possibly via the activation of cysteine-type endopeptidase activity involved in these pathways.

摘要： Background:We aimed to reveal the mechanism of functional constipation in the treatment of Atractylodes macrocephala Koidz.(AMK)and Paeonia lactiflora Pall.(PLP).Methods:The main active ingredients of AMK and PLP were screened by the Traditional Chinese Medicine Systems Pharmacology(TCMSP)platform.A database of functional constipation targets was established by GeneCard and OMIM.An“ingredient-target”network map was constructed with Cytoscape software(version 3.7.1),and molecular docking analysis was performed on the components and genes with the highest scores.The rats in the normal group were given saline,and those in the other groups were given 10 mg/kg diphenoxylate once a day for 14 days.The serum and intestinal tissue levels of adenosine monophosphate(cAMP),protein kinase A(PKA),and adenylyl cyclase(AC)of the rats and aquaporin(AQP)1,AQP3,and AQP8 were measured.Results:AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation.After treatment with AMK,PLP,or mosapride,the serum and intestinal tissue levels of AC,cAMP,and PKA were significantly downregulated.Groups receiving AMK and PLP or mosapride exhibited a reduction in the level of AQP1,AQP3,and AQP8 to varying degrees.Conclusion:Molecular docking analysis revealed that AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation.Studies have confirmed that AMK and PLP can also affect AC,cAMP,and PKA.AC,cAMP,and PKA in model rats were significantly downregulated.AQP expression is closely related to AC,cAMP,and PKA.AMK and PLP can reduce the expression of AQP1,AQP3,and AQP9 in the colon of constipated rats.

摘要： Based on network pharmacology and molecular docking technology,the similarities and differences of anti-myocardial ischemia mechanism between Salvia miltiorrhiza Bunge(SM)and Carthamus tinctorius L.(CT)were studied.Firstly,based on the traditional Chinese medicine systems pharmacology(TCMSP),the related compounds of SM and CT were obtained,and the potential targets of these compounds were collected by the target fishing method.Genecards database was used to obtain targets related to myocardial ischemia.The cross targets of CT,SM,and myocardial ischemia were then selected,and the protein-protein interaction(PPI)network was constructed based on the STRING database.The cross targets were imported into the Metascape database for Gene Oncology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Cytoscape software was used to build the topological network diagram of the drug-compound-target path.Finally,the binding ability of the active ingredient and the key target was verified by molecular docking.65 active ingredients and 38 potential targets were screened from SM,and 22 active ingredients and 58 potential targets were excavated from CT.Important targets common to SM and CT were TNF,IL6,VEGFA,AKT1,etc.The common enrichment pathways involved are fluid shear stress and atherosclerosis,IL-17 signaling pathway,pathways in cancer,and toxoplasmosis.The findings suggested that the two traditional Chinese medicines exerted the effect of myocardial ischemia through the characteristics of multiple targets,multiple pathways,and multiple compounds.

摘要： Objective: To analyze the potential mechanism of Xinyi San in treating nasal polyposis through network pharmacology. Methods: We Screened the active components and targets of Xinyi San by TCMSP database, and disease targets through GeneCards database. We constructed “disease-single drug-component-target” network through software Cytoscape 3.7.2 and constructed PPI network through STRING database. GO function and KEGG pathway enrichment were analyzed to predict its mechanism. Results: We got 162 components, 69 therapeutic targets, 88 GO items and 135 pathways. The main pathways include Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, Kaposi sarcoma-associated herpesvirus infection, Hepatitis B, Human cytomegalovirus infection, etc. Conclusion: This study preliminarily revealed the active components, targets and pathways of Xinyi San in treating nasal polyposis.

摘要： Objective:To study the potential therapeutic effect of Yigan Powder on Alzheimer’s disease(AD)comorbid Depressive Disorder with Network Pharmacology.Methods:The active ingredients of Yigan Powder were screened from Traditional Chinese Medicine Systems Pharmacology database and analysis platform(TCMSP)by ADME parameters,targets are predicted by Swiss Target Prediction database,disease targets are downloaded from GeneCards,OMIM and PharGKB database.Using R to run GO terms enrichment and KEGG pathway enrichment analysis.Protein interaction data is downloaded from the String database.Cytoscape software is used to build network.AutoDock Vina and PyMOL software are used for molecular docking.Results:There are 125 active ingredients in Yigan Powder with 953 predicted targets,85 of predicted targets are related to Alzheimer's Disease comorbid Depressive Disorder,shows highly enriched signaling pathways and biological processes.PPI network shows APP,MAPK1 and STAT3 may be important potential treatment of Alzheimer's Disease comorbid Depressive Disorder.The results of AutoDock Vina docking showed that the active ingredients of Yigan Powder had good binding activity with important receptors.Conclusion:Yigan Powder shows effect on neurotransmitter metabolism,synaptic transmission,neuroinflammation and other aspects in the treatment of Alzheimer's Disease comorbid Depressive Disorder.

摘要： Objective:This study was designed to evaluate the hypolipidemic activity of Brassica rapa and explore its mechanism by network pharmacology approach.Methods:The hypolipidemic activity of Brassica rapa aqueous extract(BRAE)was evaluated by bile salt-binding capacity and oleic acid-induced HepG2 steatosis cell model.The active compounds of Brassica rapa were collected from literature,and targets were predicted from SwissTargetPrediction and SEA Search Server platform.Cytoscape 3.7.2 software was used to construct“compound-target”network.Protein-protein interaction(PPI)network was constructed by String platform.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses based on DAVID database.Results:In vitro experiment showed that BRAE exhibited excellent bile salt-binding capacity,and the binding rates of sodium glycylcholate,sodium taurocholate and sodium deoxycholate were 36.01%,28.93%and 78.55%at 7 g.L-1,respectively.BRAE showed a significant hypolipidemic activity on steatosis cells,which can reduce the accumulation of lipid droplets and the levels of triglyceride(TG)and total cholesterol(TC)compared with the model group(P<0.05).21 active components of Brassica rapa and 682 potential targets were obtained,among which 55 targets were associated with hyperlipidemia.The“compound-target”network showed that 6-paradol,6-shogaol,benzyl-beta-D-glucopyranoside,benzyl-alpha-D-fructofuranoside and liquiritigenin were core components.PPI network and KEGG enrichment analysis found that Brassica rapa could treat hyperlipemia by regulated the core targets,such as VEGFA,IL6,EGFR and PPARG,and affected 36 signaling pathways(including starch and sucrose metabolism,galactose metabolism,insulin resistance,HIF-1,PI3K-Akt).Conclusion:This study showed that BRAE had excellent hypolipidemic activity in vitro,and preliminarily revealed the multi-component,multi-target,multi-path mechanism in the treatment of hyperlipidemia by network pharmacology approach,which provides a scientific foundation for further study.

摘要： Objective:This article uses the method of network pharmacology to study the related mechanism of Guilu Erxian Gum in the treatment of osteoporosis.Methods:Based on the TCMSP database,ETCM database,chemistry database,and DrugBank database,the potential active ingredients and related targets of Guilu Erxian Gum were obtained.The known therapeutic targets of osteoporosis were obtained from OMIM and Genecards databases,and the STRING database was used.A protein interaction network(PPI)of active ingredients-disease targets was established,and the topological parameters of the network were analyzed using Cytoscape 3.8.0 software to obtain key active ingredients and their targets.In R4.0.2,the Bioconductor data package was used to analyze the GO biological function and KEGG pathway analysis of key targets,and obtain the effective ingredients and targets of Guilu Erxian Gum for treating osteoporosis.Results:The prediction results show that Guilu Erxian Gum has 87 active ingredients and 2305 targets,and there are 4141 known therapeutic targets for osteoporosis.The two act together to obtain a total of 71 PPI core genes.The GO biological process analysis yielded 95 entries,and the KEGG pathway analysis yielded 115 pathways.Conclusion:The analysis results show that Guilu Erxian Gum may play an anti-osteoporosis effect by regulating inflammatory factors,promoting osteoblast differentiation,inhibiting osteoclast formation,and improving microcirculation.The pathways involved include TNF signaling pathways,IL-17 signaling pathway,NF-κB signaling pathway,HIF-1 signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,etc.This study provides a theoretical basis for further elucidating the pharmacological mechanism of Guilu Erxian Gum in the treatment of osteoporosis.

摘要： Liver cancer remains the dominant cause of cancer-related death, despite the advent of targeted therapies and immunotherapies. Therefore, there is an urgent need to explore novel chemotherapeutic agents and effective strategies against the cancer. There are a lot of monoterpenes and sesquiterpenoids in L. lancilimba. It has been reported that monoterpenes and sesquiterpenoids have certain anti-tumor effects. Literature investigation has also shown that Litsea lancilimba Merr. has antibacterial and antiviral effects. In this experiment, we used network pharmacology to screen the active compounds from L. lancilimba and their potential targets for treating liver cancer. Four active volatile oil ingredients and four potential targets have been identified. Our results provide the lead compound from L. lancilimba in the treatment of liver cancer.

摘要： As a traditional Chinese medicine,Curcumae Radix(CR)has exhibited anti-hepatocellular carcinoma(HCC)activity.However,the underlying molecular mechanism is still unclear.In the present study,network pharmacology was utilized to reveal the mechanism of the effects of CR in HCC.The analysis of the network results showed that the active components of CR,including curcumin,naringenin,sitosterol,demethoxycurcumin,andβ-elemene,were closely related to the screened hub-targets,such as AKT1,TP53,MAPK8,MAPK1,JUN,STAT3,VEGFA,MAPK3,IL6,TNF,CCND1,EP300,EGFR,and ESR1.GO and KEGG analyses revealed that these targets were associated with pathways in cancer,proteoglycans in cancer,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,MAPK signaling pathway,hepatitis B,hepatitis C,and other biological processes.The candidate active components of CR(curcumin and naringenin)prominently exhibited their antitumor effects by regulating PI3K-Akt signaling pathway,MAPK signaling pathway,hepatitis B and hepatitis C.This study successfully predicted,explained,and confirmed the multi-component,multi-target,and multi-channel characteristics of CR,which not only gave novel insights into the pharmacological and biological molecular mechanism of CR applying to HCC disease,but also provided a feasible method for discovering potential activated compounds from Chinese herbs.