Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP...Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP database and previous literatures to screen the active compounds which resist lung cancer activity in salvia chinensis and radix ranunculi ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The Swiss Target Prediction platform was used to predict other targets.Searching GeneCards,OMIM and DrugBank to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in salvia chinensis,18 active compounds in radix ranunculi ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways was obtained.Conclusion:The effective compounds of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets affect multiple signaling pathways and ultimately resist the proliferation,differentiation,invasion,metastasis and promote apoptosis of lung cancer cells.Evidence for further experimental study is provided by this study.展开更多
Objective:Breast cancer is a malignant tumor endangering women’s safety and health.Clinical medication experience and related studies show that the drug pairs Tubeimu-Zhebeimu has an excellent therapeutic effect on p...Objective:Breast cancer is a malignant tumor endangering women’s safety and health.Clinical medication experience and related studies show that the drug pairs Tubeimu-Zhebeimu has an excellent therapeutic effect on patients with breast cancer,but its treatment mechanism is unclear.In this study,network pharmacology and molecular docking were used to analyze and explore the mechanism of“Tubeimu-Zhebeimu”in treating breast cancer.Methods:Traditional Chinese Medicine Database and Analysis Platform were used to retrieve the chemical constituents of Tubeimu and Zhebeimu,and the relevant targets were predicted through the Swiss Target Prediction Database.Searching the Gene cards,Therapeutic Target Database and Disgenet Database with the keywords“breast cancer”,“mammary cancer”and“mammary adenocarcinoma”obtain disease-related targets.We intersect the disease target with the drug target to obtain the potential drug therapy target.Then the data was imported into Cytoscape 3.9.1 software to construct a compound network of“Disease-Target-Component-Drug”,and the network.Subsequently,using the String Database a“protein-protein interaction network”was constructed and imported into Cytoscape 3.9.1 software for structural optimization and network topology analysis.DAVID was used for Gene Ontolog function enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses,and the results were visualized.The core targets were molecularly docked through AutoDockTools-1.5.6 software and Auto Dock Vina 1.1.2 software.Results:The results showed that the 20 active ingredients in the“Tubeimu-Zhebeimu”includingβ-sitosterol,Chaksine,saponins,and peimuocinine,can treat breast cancer through 139 potential targets including AKT1,AR,TP53,ESR1.Conclusion:The specific mechanism of the drug pairs Tubeimu-Zhebeimu treating breast cancer may be controlling human hormone levels,inducing cell apoptosis,and participating in the P53 protein signaling pathway and PI3K/Akt/mTOR signaling pathway.展开更多
Objective:Using data mining method to dig and sort out the prescriptions with Acorus tatarinowiiPolygala tenuifolia drug pair,and summarize the medication characteristics and compatibility of their prescriptions after...Objective:Using data mining method to dig and sort out the prescriptions with Acorus tatarinowiiPolygala tenuifolia drug pair,and summarize the medication characteristics and compatibility of their prescriptions after preliminary screening.Methods:By searching the Dictionary of Traditional Chinese Medicine Prescriptions,a standardized database of prescriptions was established,and the properties,tastes and meridian tropism of prescriptions were classified,and the indications of prescriptions and core combinations of traditional Chinese medicines were analyzed.Results:178 prescriptions were collected,of which 210 were related.Most of the drugs were warm in nature and sweet in taste,and mainly return to the heart and kidney meridians.Under the same confidence and different support,the core drug combination for treating brain diseases was Acorus tatarinowiiPolygala tenuifolia-Ginseng,and the core drug combination for treating asthenia was Acorus tatarinowii-Poria cocos-Rehmannia glutinosa-Polygala tenuifolia.Conclusion:The compatibility characteristics of the prescriptions containing Acorus Tatarinowii and Polygala tenuifolia in the Dictionary of Traditional Chinese Medicine Prescriptions are remarkable,which provides reference for scientific guidance of clinical rational drug use and basic research of prescriptions containing Acorus tatarinowii and Polygala tenuifolia.展开更多
Active volatile components in drug pair(DP)Herba Ephedrae-Ramulus Cinnamomi(HE-RC),single drug HE and RC were analyzed by gas chromatography/mass spectrometry(GC/MS),chemometric resolution method(CRM)and overall volum...Active volatile components in drug pair(DP)Herba Ephedrae-Ramulus Cinnamomi(HE-RC),single drug HE and RC were analyzed by gas chromatography/mass spectrometry(GC/MS),chemometric resolution method(CRM)and overall volume integration.By means of CRM,the two-dimensional data obtained from GC-MS instruments were resolved into a pure chromatogram and a mass spectrum of each chemical compound.In total,97,62,and 78 volatile chemical components in volatile oil of HE,RC,and DP HE-RC,were respectively determined qualitatively and quantitatively,accounting for 90.08%,91.62%,and 89.76% total contents of volatile oil of HE,RC,and DP HE-RC respectively.It is further demonstrated that the numbers of volatile components of DP HE-RC are almost the sum of those of two single drugs,but some relative contents of them are changed.Some new components,such as 1,6-dimethylhepta-1,3,5-triene,tetracyclo[4.2.1.1(2,5).0(9,10)]deca-3,7-diene,globulol and(E,E)-6,10,14-trimethyl-5,9,13-pentadecatrien-2-one are found in DP HE-RC because of chemical reactions and physical changes during decoction.展开更多
The COVID-19 pandemic has resulted in excess deaths worldwide.Conventional antiviral medicines have been used to relieve the symptoms,with limited therapeutic effect.In contrast,Lianhua Qingwen Capsule is reported to ...The COVID-19 pandemic has resulted in excess deaths worldwide.Conventional antiviral medicines have been used to relieve the symptoms,with limited therapeutic effect.In contrast,Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect.The current review aims to:1)uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19;2)verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis;3)investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule;and 4)clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs.Numerous bioactive ingredients in Lianhu Qingwen,such as quercetin,naringenin,β-sitosterol,luteolin,and stigmasterol,were identified to target host cytokines,and to regulate the immune defence in response to COVID-19.Genes including androgen receptor(AR),myeloperoxidase(MPO),epidermal growth factor receptor(EGFR),insulin(INS),and aryl hydrocarbon receptor(AHR)were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19.Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19.Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19.In conclusion,the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed.Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.展开更多
OBJECTIVE:To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair(ECD)and investigate its efficacy on polycystic ovary syndrome(PCOS),and its possible mechanism...OBJECTIVE:To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair(ECD)and investigate its efficacy on polycystic ovary syndrome(PCOS),and its possible mechanism in a rat model of PCOS.METHODS:A network pharmacology approach involving a characteristic drug assessment,active compound and target prediction,PCOS gene collection as well as network analysis was employed.The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target.RESULTS:Six networks were constructed,an active compound-target network for the ECD(C-T network),a drug-target network(D-T network),a related genes network,a targets interaction network,a key genes interaction network,and a gene-pathway network.A total of 41 compounds and 261 targets were identified for the ECD,232 PCOS-related genes,31 cogenes,and 14 pathways.These pathways may be involved in the efficacy of ECD on PCOS.The proteins most involved in the signal pathways for all targets were AKT1,IL6,INSR,ESR,and GSK3B.The AKT1 target was selected for experimental verification.Based on the Western blot and real-time PCR results,the expression of AKT1 in the PCOS model varied after treatment with ECD.CONCLUSIONS:Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS.AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.展开更多
Objective:Using network pharmacology to explore the mechanism of the'invigorating qi and promoting blood circulation'drug pair Ginseng-Danshen(Salvia miltiorrhiza)on treatment of ischemic heart disease(IHD).Me...Objective:Using network pharmacology to explore the mechanism of the'invigorating qi and promoting blood circulation'drug pair Ginseng-Danshen(Salvia miltiorrhiza)on treatment of ischemic heart disease(IHD).Methods:The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential targets of the pair were identified.The pharmacodynamics of the pair was analyzed using network pharmacology.The targets of IHD were identified by database screening.Using protein-protein interaction network,the interaction targets of Ginseng-Danshen on IHD were constructed.A"constituent-target-disease"interaction network was constructed using Cytoscape software,Gene Ontology(GO)term enrichment analysis and biological pathway enrichment analysis were carried out,and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated.Results:Seventeen active constituents and 53 targets were identified from ginseng,53 active constituents and 61 targets were identified from Danshen,and 32 protein targets were shared by ginseng and Danshen.Twenty GO terms were analyzed,including cytokine receptor binding,cytokine activity,heme binding,and antioxidant activity.Sixty Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways were analyzed,including phosphatidylinositol 3-kinase-serine-threonine kinase(PI3 K-AKT)signaling pathway,p53 signaling pathway,interleukin 17 signaling pathway,tumor necrosis factor signaling pathway,and the advanced glycation end product(AGE)-the receptor for AGE(RAGE)signaling pathway in diabetic complications.Conclusion:The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody,inhibiting the production of peroxides,removing the endogenous oxygen free radicals,regulating the expression of inflammatory factors,reducing myocardial cell apoptosis and promoting vascular regeneration.展开更多
Objective: Premature ovarian failure (POF) is a disease characterized by irregular menstruation and results in infertility which markedly affects the reproductive health of women. TheSalvia miltiorrhiza-Codonopsis pil...Objective: Premature ovarian failure (POF) is a disease characterized by irregular menstruation and results in infertility which markedly affects the reproductive health of women. TheSalvia miltiorrhiza-Codonopsis pilosula drug pair is effective at treating POF;however, knowledge of the mechanisms ofS. miltiorrhiza-C. pilosula in the treatment of POF is lacking. Thus, we carried out network pharmacology and molecular docking to clarify the mechanisms of this drug pair.Methods: The core components and targets ofS. miltiorrhiza-C. pilosula were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database and UniProt database, and the disease targets related to POF were searched using different tools to obtain the overlapping target genes ofS. miltiorrhiza andC. pilosula. A protein interaction network of the intersection target was constructed using STRING database, and the network of "traditional Chinese medicine-active ingredient-intersection target-disease" and "pathways-targets" was constructed using Cytoscape 3.8.0. The DAVID online tool was also used to determine the gene ontology functions and Kyoto Encyclopedia of Genes and Genomes pathways associated with the intersection target genes. Finally, the binding ability of the drug to the active components and potential targets were predicted using molecular docking.Results: S. miltiorrhizae-C. pilosula had 72 active components, 128 targets, 3,775 POF targets, and 106 common targets. The potential targets were mainly related to the biological processes of DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, transcription factor activity, steroid receptor activity, and hypoxia response. Further, the Kyoto Encyclopedia of Genes and Genomes enrichment pathways included PI3K-Akt signaling pathway, apoptosis, interleukin (IL)-17 signaling pathway, relaxin signaling pathway, and other biological pathways.Conclusion(s): S. miltiorrhiza-C. pilosula can inhibit ovarian granulosa cell apoptosis and improve ovarian hemodynamics through multiple targets and multiple pathways and help treat POF.展开更多
目的基于网络药理学和分子对接方法探究“麦冬-五味子”药对治疗心肌纤维化的作用机制。方法运用TCMSP数据库及HERB数据库筛选“麦冬-五味子”药对药物成分和靶点,运用GeneCards数据库、Disgenet数据库、OMIM数据库筛选疾病靶点,获取共...目的基于网络药理学和分子对接方法探究“麦冬-五味子”药对治疗心肌纤维化的作用机制。方法运用TCMSP数据库及HERB数据库筛选“麦冬-五味子”药对药物成分和靶点,运用GeneCards数据库、Disgenet数据库、OMIM数据库筛选疾病靶点,获取共同靶点;通过Cytoscape软件构建“药物活性成分-疾病-靶点”网络模型;利用微生信平台进行基因本体论功能富集分析(gene ontology,GO)和京都基因与基因组百科全书富集分析(kyoto encyclopedia of genes and genomes,KEGG);利用STRING数据库构建蛋白互作网络;通过Auto Dock Tools1.5.6软件进行分子对接验证。结果“麦冬-五味子”药对中共筛选得到戈米辛M2、五味子酚乙、麦冬二氢高异黄酮B等85个活性成分,主要作用于HSP90AA1、AKT1、SRC等163个心肌纤维化靶点上,主要富集在脂质与动脉粥样硬化信号通路、糖尿病并发症中的age-rage信号通路、癌症发病途径信号通路等相关通路上。结论“麦冬-五味子”药对主要通过调控炎性反应、氧化应激、脂质沉积、细胞增殖凋亡等多种生物过程来抑制心肌纤维化。展开更多
基金National Natural Science Foundation of China(No.1673961)Beijing Natural Science Foundation Project(No.7172186)Special Training Program for Outstanding Young Scientific and Technological Talents(innovation)of Chinese Academy of Traditional Chinese Medicine(No.ZZ13-YQ-028)。
文摘Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP database and previous literatures to screen the active compounds which resist lung cancer activity in salvia chinensis and radix ranunculi ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The Swiss Target Prediction platform was used to predict other targets.Searching GeneCards,OMIM and DrugBank to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in salvia chinensis,18 active compounds in radix ranunculi ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways was obtained.Conclusion:The effective compounds of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets affect multiple signaling pathways and ultimately resist the proliferation,differentiation,invasion,metastasis and promote apoptosis of lung cancer cells.Evidence for further experimental study is provided by this study.
文摘Objective:Breast cancer is a malignant tumor endangering women’s safety and health.Clinical medication experience and related studies show that the drug pairs Tubeimu-Zhebeimu has an excellent therapeutic effect on patients with breast cancer,but its treatment mechanism is unclear.In this study,network pharmacology and molecular docking were used to analyze and explore the mechanism of“Tubeimu-Zhebeimu”in treating breast cancer.Methods:Traditional Chinese Medicine Database and Analysis Platform were used to retrieve the chemical constituents of Tubeimu and Zhebeimu,and the relevant targets were predicted through the Swiss Target Prediction Database.Searching the Gene cards,Therapeutic Target Database and Disgenet Database with the keywords“breast cancer”,“mammary cancer”and“mammary adenocarcinoma”obtain disease-related targets.We intersect the disease target with the drug target to obtain the potential drug therapy target.Then the data was imported into Cytoscape 3.9.1 software to construct a compound network of“Disease-Target-Component-Drug”,and the network.Subsequently,using the String Database a“protein-protein interaction network”was constructed and imported into Cytoscape 3.9.1 software for structural optimization and network topology analysis.DAVID was used for Gene Ontolog function enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses,and the results were visualized.The core targets were molecularly docked through AutoDockTools-1.5.6 software and Auto Dock Vina 1.1.2 software.Results:The results showed that the 20 active ingredients in the“Tubeimu-Zhebeimu”includingβ-sitosterol,Chaksine,saponins,and peimuocinine,can treat breast cancer through 139 potential targets including AKT1,AR,TP53,ESR1.Conclusion:The specific mechanism of the drug pairs Tubeimu-Zhebeimu treating breast cancer may be controlling human hormone levels,inducing cell apoptosis,and participating in the P53 protein signaling pathway and PI3K/Akt/mTOR signaling pathway.
基金Shaanxi Provincial Administration of Traditional Chinese Medicine:Chang’an Stroke School Inheritance Studio(Shaanxi Traditional Chinese Medicine Fa[2018]No.40)Key R&D Plan of Shaanxi Science and Technology Department(2020SF-342)。
文摘Objective:Using data mining method to dig and sort out the prescriptions with Acorus tatarinowiiPolygala tenuifolia drug pair,and summarize the medication characteristics and compatibility of their prescriptions after preliminary screening.Methods:By searching the Dictionary of Traditional Chinese Medicine Prescriptions,a standardized database of prescriptions was established,and the properties,tastes and meridian tropism of prescriptions were classified,and the indications of prescriptions and core combinations of traditional Chinese medicines were analyzed.Results:178 prescriptions were collected,of which 210 were related.Most of the drugs were warm in nature and sweet in taste,and mainly return to the heart and kidney meridians.Under the same confidence and different support,the core drug combination for treating brain diseases was Acorus tatarinowiiPolygala tenuifolia-Ginseng,and the core drug combination for treating asthenia was Acorus tatarinowii-Poria cocos-Rehmannia glutinosa-Polygala tenuifolia.Conclusion:The compatibility characteristics of the prescriptions containing Acorus Tatarinowii and Polygala tenuifolia in the Dictionary of Traditional Chinese Medicine Prescriptions are remarkable,which provides reference for scientific guidance of clinical rational drug use and basic research of prescriptions containing Acorus tatarinowii and Polygala tenuifolia.
基金Project (01962502) supported by the Natural Science Foundation of Hunan Province, China
文摘Active volatile components in drug pair(DP)Herba Ephedrae-Ramulus Cinnamomi(HE-RC),single drug HE and RC were analyzed by gas chromatography/mass spectrometry(GC/MS),chemometric resolution method(CRM)and overall volume integration.By means of CRM,the two-dimensional data obtained from GC-MS instruments were resolved into a pure chromatogram and a mass spectrum of each chemical compound.In total,97,62,and 78 volatile chemical components in volatile oil of HE,RC,and DP HE-RC,were respectively determined qualitatively and quantitatively,accounting for 90.08%,91.62%,and 89.76% total contents of volatile oil of HE,RC,and DP HE-RC respectively.It is further demonstrated that the numbers of volatile components of DP HE-RC are almost the sum of those of two single drugs,but some relative contents of them are changed.Some new components,such as 1,6-dimethylhepta-1,3,5-triene,tetracyclo[4.2.1.1(2,5).0(9,10)]deca-3,7-diene,globulol and(E,E)-6,10,14-trimethyl-5,9,13-pentadecatrien-2-one are found in DP HE-RC because of chemical reactions and physical changes during decoction.
基金Hong Kong Development Fund(Nos.19SB2/002A,19B2/001A_R1,and 19B1_1/002A_R2)Wong’s donation(No.20006276)a donation from the Gaia Family Trust of New Zealand(No.200007008).
文摘The COVID-19 pandemic has resulted in excess deaths worldwide.Conventional antiviral medicines have been used to relieve the symptoms,with limited therapeutic effect.In contrast,Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect.The current review aims to:1)uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19;2)verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis;3)investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule;and 4)clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs.Numerous bioactive ingredients in Lianhu Qingwen,such as quercetin,naringenin,β-sitosterol,luteolin,and stigmasterol,were identified to target host cytokines,and to regulate the immune defence in response to COVID-19.Genes including androgen receptor(AR),myeloperoxidase(MPO),epidermal growth factor receptor(EGFR),insulin(INS),and aryl hydrocarbon receptor(AHR)were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19.Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19.Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19.In conclusion,the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed.Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.
基金Supported by the Natural Science Foundation of Liaoning Province:Functional Identification and Molecular Regulation of mi R-26b-5p Associated with Premature Ovarian Failure(No.20170540373)Jinzhou Foundation for Science and Technology:Study on the Rule and Mechanism of Prescriptions for Premature Ovarian Failure Based on Network Pharmacology,China(No.16B1G35)。
文摘OBJECTIVE:To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair(ECD)and investigate its efficacy on polycystic ovary syndrome(PCOS),and its possible mechanism in a rat model of PCOS.METHODS:A network pharmacology approach involving a characteristic drug assessment,active compound and target prediction,PCOS gene collection as well as network analysis was employed.The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target.RESULTS:Six networks were constructed,an active compound-target network for the ECD(C-T network),a drug-target network(D-T network),a related genes network,a targets interaction network,a key genes interaction network,and a gene-pathway network.A total of 41 compounds and 261 targets were identified for the ECD,232 PCOS-related genes,31 cogenes,and 14 pathways.These pathways may be involved in the efficacy of ECD on PCOS.The proteins most involved in the signal pathways for all targets were AKT1,IL6,INSR,ESR,and GSK3B.The AKT1 target was selected for experimental verification.Based on the Western blot and real-time PCR results,the expression of AKT1 in the PCOS model varied after treatment with ECD.CONCLUSIONS:Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS.AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.
基金Supported by the National Natural Science Foundation of China(No.81774145)Youth Program of National Natural Science Foundation of China(No.81503292)National Key Basic Research and Development Program(No.2015cb554406)。
文摘Objective:Using network pharmacology to explore the mechanism of the'invigorating qi and promoting blood circulation'drug pair Ginseng-Danshen(Salvia miltiorrhiza)on treatment of ischemic heart disease(IHD).Methods:The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential targets of the pair were identified.The pharmacodynamics of the pair was analyzed using network pharmacology.The targets of IHD were identified by database screening.Using protein-protein interaction network,the interaction targets of Ginseng-Danshen on IHD were constructed.A"constituent-target-disease"interaction network was constructed using Cytoscape software,Gene Ontology(GO)term enrichment analysis and biological pathway enrichment analysis were carried out,and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated.Results:Seventeen active constituents and 53 targets were identified from ginseng,53 active constituents and 61 targets were identified from Danshen,and 32 protein targets were shared by ginseng and Danshen.Twenty GO terms were analyzed,including cytokine receptor binding,cytokine activity,heme binding,and antioxidant activity.Sixty Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways were analyzed,including phosphatidylinositol 3-kinase-serine-threonine kinase(PI3 K-AKT)signaling pathway,p53 signaling pathway,interleukin 17 signaling pathway,tumor necrosis factor signaling pathway,and the advanced glycation end product(AGE)-the receptor for AGE(RAGE)signaling pathway in diabetic complications.Conclusion:The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody,inhibiting the production of peroxides,removing the endogenous oxygen free radicals,regulating the expression of inflammatory factors,reducing myocardial cell apoptosis and promoting vascular regeneration.
基金This work was supported by the second construction project of National Traditional Chinese Medicine Academic Schools Inheritance Studio of the State Administration of Traditional Chinese Medicine"Zhu's Gynecology School Inheritance Studio"Clinical Medicine Project of Shanghai"Science and Technology Innovation Action Plan",China(19401971300)Graduate Student Innovation Ability Project of Shanghai University of Traditional Chinese Medicine,China(Y2021017).
文摘Objective: Premature ovarian failure (POF) is a disease characterized by irregular menstruation and results in infertility which markedly affects the reproductive health of women. TheSalvia miltiorrhiza-Codonopsis pilosula drug pair is effective at treating POF;however, knowledge of the mechanisms ofS. miltiorrhiza-C. pilosula in the treatment of POF is lacking. Thus, we carried out network pharmacology and molecular docking to clarify the mechanisms of this drug pair.Methods: The core components and targets ofS. miltiorrhiza-C. pilosula were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database and UniProt database, and the disease targets related to POF were searched using different tools to obtain the overlapping target genes ofS. miltiorrhiza andC. pilosula. A protein interaction network of the intersection target was constructed using STRING database, and the network of "traditional Chinese medicine-active ingredient-intersection target-disease" and "pathways-targets" was constructed using Cytoscape 3.8.0. The DAVID online tool was also used to determine the gene ontology functions and Kyoto Encyclopedia of Genes and Genomes pathways associated with the intersection target genes. Finally, the binding ability of the drug to the active components and potential targets were predicted using molecular docking.Results: S. miltiorrhizae-C. pilosula had 72 active components, 128 targets, 3,775 POF targets, and 106 common targets. The potential targets were mainly related to the biological processes of DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, transcription factor activity, steroid receptor activity, and hypoxia response. Further, the Kyoto Encyclopedia of Genes and Genomes enrichment pathways included PI3K-Akt signaling pathway, apoptosis, interleukin (IL)-17 signaling pathway, relaxin signaling pathway, and other biological pathways.Conclusion(s): S. miltiorrhiza-C. pilosula can inhibit ovarian granulosa cell apoptosis and improve ovarian hemodynamics through multiple targets and multiple pathways and help treat POF.
文摘目的基于网络药理学和分子对接方法探究“麦冬-五味子”药对治疗心肌纤维化的作用机制。方法运用TCMSP数据库及HERB数据库筛选“麦冬-五味子”药对药物成分和靶点,运用GeneCards数据库、Disgenet数据库、OMIM数据库筛选疾病靶点,获取共同靶点;通过Cytoscape软件构建“药物活性成分-疾病-靶点”网络模型;利用微生信平台进行基因本体论功能富集分析(gene ontology,GO)和京都基因与基因组百科全书富集分析(kyoto encyclopedia of genes and genomes,KEGG);利用STRING数据库构建蛋白互作网络;通过Auto Dock Tools1.5.6软件进行分子对接验证。结果“麦冬-五味子”药对中共筛选得到戈米辛M2、五味子酚乙、麦冬二氢高异黄酮B等85个活性成分,主要作用于HSP90AA1、AKT1、SRC等163个心肌纤维化靶点上,主要富集在脂质与动脉粥样硬化信号通路、糖尿病并发症中的age-rage信号通路、癌症发病途径信号通路等相关通路上。结论“麦冬-五味子”药对主要通过调控炎性反应、氧化应激、脂质沉积、细胞增殖凋亡等多种生物过程来抑制心肌纤维化。