Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predic...Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predict the miRNA targets of Erxian decoction for the treatment of postmenopausal osteoporosis,and the results were validated by clinical trials.Methods:In this study,we identified possible targets of Erxian decoction in osteoporosis by means of network pharmacological analysis and bioinformatic prediction.Fifteen cases of postmenopausal osteoporosis with kidney Yin and Yang deficiency(In traditional Chinese medicine,kidney Yin nourishes and moistens the tissues of the internal organs of the body,while kidney Yang promotes and warms the tissues of the internal organs of the body.)were treated with Erxian decoction for four weeks,and serum bone metabolism indices(P1NP,osteocalcin,andβ-CTX)and miRNA-335-5p expression were measured before and after treatment.Results:The constructed miRNA postmenopausal osteoporosis related gene network of the effective compound of the Erxian decoction has 296 points and 981 edges.The 39 postmenopausal osteoporosis related genes regulated by miRNA-335-5p were enriched in ossification,while the signaling pathways were enriched in rheumatoid arthritis,the Toll signaling pathway,the HIF-1 signaling pathway,and the MAPK signaling pathway.After taking Erxian decoction,the expression of the serum bone formation index(P1NP,osteocalcin)and miRNA-335-5p gene expression levels increased significantly.The alterations in P1NP and osteocalcin were correlated with the changes in miRNA-335-5p.Conclusion:Circulating miRNA-335-5p may serve as an important target of Erxian decoction in the treatment of postmenopausal women.The effect of Erxian decoction on bone formation is significant,but the underlying mechanism requires further investigation.展开更多
[Objectives]To explore the clinical effect of Erxian decoction on relieving low back pain after percutaneous vertebroplasty(PVP)of vertebral compression fracture caused by postmenopausal osteoporosis(PMOP).[Methods]Ni...[Objectives]To explore the clinical effect of Erxian decoction on relieving low back pain after percutaneous vertebroplasty(PVP)of vertebral compression fracture caused by postmenopausal osteoporosis(PMOP).[Methods]Ninety patients who were treated in Suzhou TCM Hospital from September 2021 to January 2023 were randomly divided into three groups:traditional Chinese medicine group(n=30),western medicine group(n=30)and blank group(n=30).The patients in all the three groups were treated with basic anti-osteoporosis drugs.The patients in the traditional Chinese medicine group were treated with Erxian decoction after PVP,and those in the western medicine group were treated with celecoxib to relieve pain after operation.The visual analogue(VAS)score,Oswestry dysfunction index(ODI)score,TCM syndrome score and serum indexes such as interleukin-6(IL-6)and estrogen E2 were recorded before treatment and 2 weeks,1 month and 3 months after treatment.[Results](i)In terms of pain relief,the VAS score of the western medicine group was lower than that of the traditional Chinese medicine group after 2 weeks of treatment,but there was no significant difference in VAS score between the two groups after 1 month and 3 months,and the pain improvement of the two groups was better than that of the blank group.(ii)After 3 months of treatment,the ODI score in the traditional Chinese medicine group was lower than that in the western medicine group,and the improvement of TCM syndrome in the traditional Chinese medicine group was better than that in the other two groups 1 and 3 months after treatment(P<0.05).(iii)The level of IL-6 in the western medicine group was lower than that in the other groups after 2 weeks,and there was no significant difference between the two groups after 3 months of treatment.After 3 months of treatment,the level of E2 in the traditional Chinese medicine group was higher than that before treatment and higher than that in the western medicine group and the blank group,but there was no significant difference between the two groups(P>0.05).[Conclusions]Both Erxian decoction and non-steroidal anti-inflammatory drugs can relieve residual low back pain after PVP,and their long-term effects are similar,but Erxian decoction has more advantages in alleviating pain,muscle and joint pain and sensory abnormalities in postmenopausal women.Moreover,it is safe and reliable,and is worthy of clinical application.展开更多
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,a...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.展开更多
Objective:To explore the mechanism of Erxian Decoction in the treatment of premature ovarian failure.Methods:Based on the method of network pharmacology and molecular docking,the active ingredients of each drug in Erx...Objective:To explore the mechanism of Erxian Decoction in the treatment of premature ovarian failure.Methods:Based on the method of network pharmacology and molecular docking,the active ingredients of each drug in Erxian Decoction were obtained by searching the TCMSP database;the premature ovarian failure disease targets were collected from the GeneCards,OMIM,PharmGkb and Drugbank databases,and the active ingredients and the disease gene targets were collected Click the intersection to get the predictive target of Erxian Decoction for the treatment of premature ovarian failure.Use Cytoscape 3.8.0 to construct a"drug-component-target-disease"network;construct a protein interaction network(PPI)and streamline the core network through STRING database and Cytoscape;use R Studio software to enrich the Erxiantang treatment POF with GO And KEGG pathway enrichment analysis.Use molecular docking technology to verify the results of the"drug-component-target-disease"network.Results:68 main active ingredients were screened,involving 182 gene targets,among which the main active ingredients include Quercetin,Luteolin,Kaempferol,etc.;The core target genes include RB1,TP53,FOS,CDKN1A,ESR1,AKT1,MAPK1,TNF,etc.;GO enrichment items were obtained,including the 2545 Biological Process(BP),89 Cellular Component(CC),212 Molecular Function(MF);KEGG pathways,including PI3K-Akt signaling pathway,MAPK signaling pathway,and AGE-RAGE signaling pathway in diabetic complications.The verification of the molecular docking results indicated that the main active ingredient has a good binding activity with the core target.Conclusion:This study preliminarily revealed that Erxian Decoction may play a role in the treatment of POF through multi-component,multi-target,and multi-channel synergy,which provides a reference for the next in-depth research.展开更多
Objective:This paper aims to explore the mech-anism of Erxian Decoction in treating insoimnia by means of network pharmacology research method.Methods:The com-ponents and related targets of Erxian Decoction are screen...Objective:This paper aims to explore the mech-anism of Erxian Decoction in treating insoimnia by means of network pharmacology research method.Methods:The com-ponents and related targets of Erxian Decoction are screened by TCMSP database.Disease targets are obtained by OMMM and Gene Cards database,and the common targets of drugs and diseases are obtained.The network diagram of"drug-coumponent-disease-target"is constructed and analyzed.STRING database constructs PPI network and finds the core target.GO and KEGG enrichnent analysis are employed on intersection targets.Results:84 effective components and 169 drug targets.of Erxian Decoction as well as 2614 targets of insomnia are screened out.Seventy-two intersection targets are selected by Venn diagram,and the core targets include IL-6,TNF,VEGFA and L-1β.These intersection targets contain 404 GO processes and 67 KEGG pathways,including TOLL-like receptor signaling pathway,cyclic adenosine monophosphate(CAMP)signaling pathway and tumor necrosis factor(TNF)signaling pathway.Conclusion:Erxian Decoction may play a role in treating insomnia by regulating TOLL-like receptor signaling pathway,cyclic adenosine monophosphate(CAMP)signaling pathway and tumnor necrosis factor(TNF)signaling pathway.展开更多
目的:基于网络药理学探讨二仙汤“异病同治”乳腺增生和围绝经期综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选二仙汤中...目的:基于网络药理学探讨二仙汤“异病同治”乳腺增生和围绝经期综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选二仙汤中6味中药的活性成分并预测其潜在靶点;通过人类基因数据库(the human gene database,GeneCards)及在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)平台检索乳腺增生和围绝经期综合征的疾病靶点,借助Venn在线工具构建药物与两种疾病的交集靶点。运用Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”网络;利用STRING数据库构建PPI网络,按Dgree值大于等于平均值进一步筛选核心靶点;采用DAVID数据库进行基因本体论(gene ontology,GO)富集分析,同时实现京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果 :根据口服生物利用度(oral bioavailability,OB)≥30%和药物类药性(druglikeness,DL)≥0.18筛选得到二仙汤有效活性成分104个,预测潜在作用靶点147个;通过筛选得到乳腺增生靶点4153个,围绝经期综合征靶点155个,药物与疾病的交集靶点29个,其中IL-6、VEGFA、TNF、TP53、ESR1、CAT、IL-1β等可能是二仙汤治疗乳腺增生和围绝经期综合征的关键靶点。活性成分及靶点主要参与DNA模板转录正调控、基因表达的正调控、胞外间隙、胞外区、类固醇结合、酶结合等;靶基因主要富集在TNF、NOD样体、HIF-1、癌症、PI3K-Akt等信号通路。结论:二仙汤可能通过调控PI3K-Akt、HIF-1等信号通路达到防治乳腺增生和围绝经期综合征的目的。展开更多
Objective:To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction(二仙汤,EXD)as a treatment for premature ovarian failure(POF)using a syste...Objective:To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction(二仙汤,EXD)as a treatment for premature ovarian failure(POF)using a systems pharmacology approach.Methods:The compounds present in EXD were obtained from three databases.The active ingredient was identified by analyzing the values of oral bioavailability(OB),drug-like ness(DL),and Lipin ski's rule(LR).The active in gredients were further searched in research articles,drug targets in the DrugBank database,and the C-T and T-P networks,as well as by pathway analysis using the Cytoscape platform.Results:A total of 728 compounds were identified in EXD.Of these,59 were identified as active compounds that conformed to the criteria with OB>30%and DL>0.18.By further searches in the literature,126 related targets were ide ntified that could in teract with the active compounds.Additi on ally,it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immline system,modulation of estrogen levels,and anti-oxidative activities,and that it may act in a synergistic or cooperative manner with other therapeutic agents.Conclusions:The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF.The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.展开更多
Objective To evaluate the effect of Guilu Erxian Glue(龟鹿二仙胶,GEG)on cyclophosphamide(CTX)-induced bone marrow hematopoietic stem cells(HSCs)senescence in mice and explore the underlying mechanism.Methods The H22 l...Objective To evaluate the effect of Guilu Erxian Glue(龟鹿二仙胶,GEG)on cyclophosphamide(CTX)-induced bone marrow hematopoietic stem cells(HSCs)senescence in mice and explore the underlying mechanism.Methods The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally(i.p.)with 5×10^6/mL H22 cells per mouse.Fifty tumor-bearing mice were divided into the control,model,pifithrin-α,GEG,and GEG+pifithrin-αgroups using a random number table,10 mice in each group.CTX(100 mg/kg i.p.)was administrated to mice from day 1 to day 3(d1–d3)continuously except for the control group.The mice in the pifithrin-α,GEG and GEG+pifithrin-αgroups were treated with pifithrin-α(2.2 mg/(kg·d)i.p.)for 6 consecutive days(d4–d9),GEG(9.5 g/(kg·d)i.p.)for 9 consecutive days(d1–d9),and GEG plus pifithrin-α,respectively.HSCs were collected after 9-d drug treatment.The anti-aging effect of GEG was studied by cell viability,cell cycle,andβ-galactosidase(β-gal)assays.The mRNA and protein expressions of cyclin-dependent kinase 2(CDK2),CDK4,inhibitor of cyclin-dependent kinase 4a encoding the tumor suppressor protein p16^(p16^INK4a),p21^Cip1/Waf1,p53,and phosphorylated retinoblastoma(pRb)were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot,respectively.Results Compared with the model group,GEG increased cell viability as well as proliferation(P<0.05 or P<0.01)and reducedβ-gal expression.Furthermore,GEG significantly decreased the expressions of p16^INK4a,p53 and p21^Cip1/Waf1 proteins,and increased the expressions of CDK2,CDK4 and pRb proteins compared with the model group(P<0.05 or P<0.01).Conclusion GEG can alleviate CTX-induced HSCs senescence in mice,and the p16^INK4a-Rb signaling pathway might be the underlying mechanism.展开更多
Erxian Tang (二仙汤,EXT) is a Chinese herbal formula developed for the treatment of menopausal syndrome in women. In the past 50 years, EXT has shown positive efficacy in the treatment of many chronic diseases in TCM,...Erxian Tang (二仙汤,EXT) is a Chinese herbal formula developed for the treatment of menopausal syndrome in women. In the past 50 years, EXT has shown positive efficacy in the treatment of many chronic diseases in TCM, involving syndrome types of Shen (肾) yin-yang deficiency, yin-deficiency caused yang-flourishing, and disharmony of Chong-Ren meridian. Experimental studies have revealed that EXT has multiple pharmacological actions on such multiple targets as hypothalamus-pituitary-target gland axis, immune function and free radical metabolism, etc.展开更多
基金supported by Suzhou Special Project for Diagnosis and Treatment Technology of Clinical Key Diseases(No.LCZX202127)。
文摘Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predict the miRNA targets of Erxian decoction for the treatment of postmenopausal osteoporosis,and the results were validated by clinical trials.Methods:In this study,we identified possible targets of Erxian decoction in osteoporosis by means of network pharmacological analysis and bioinformatic prediction.Fifteen cases of postmenopausal osteoporosis with kidney Yin and Yang deficiency(In traditional Chinese medicine,kidney Yin nourishes and moistens the tissues of the internal organs of the body,while kidney Yang promotes and warms the tissues of the internal organs of the body.)were treated with Erxian decoction for four weeks,and serum bone metabolism indices(P1NP,osteocalcin,andβ-CTX)and miRNA-335-5p expression were measured before and after treatment.Results:The constructed miRNA postmenopausal osteoporosis related gene network of the effective compound of the Erxian decoction has 296 points and 981 edges.The 39 postmenopausal osteoporosis related genes regulated by miRNA-335-5p were enriched in ossification,while the signaling pathways were enriched in rheumatoid arthritis,the Toll signaling pathway,the HIF-1 signaling pathway,and the MAPK signaling pathway.After taking Erxian decoction,the expression of the serum bone formation index(P1NP,osteocalcin)and miRNA-335-5p gene expression levels increased significantly.The alterations in P1NP and osteocalcin were correlated with the changes in miRNA-335-5p.Conclusion:Circulating miRNA-335-5p may serve as an important target of Erxian decoction in the treatment of postmenopausal women.The effect of Erxian decoction on bone formation is significant,but the underlying mechanism requires further investigation.
基金Supported by National Natural Science Foundation of China(82074456)Suzhou Health Commission,Gusu Health Talent Project(GSWS2020090).
文摘[Objectives]To explore the clinical effect of Erxian decoction on relieving low back pain after percutaneous vertebroplasty(PVP)of vertebral compression fracture caused by postmenopausal osteoporosis(PMOP).[Methods]Ninety patients who were treated in Suzhou TCM Hospital from September 2021 to January 2023 were randomly divided into three groups:traditional Chinese medicine group(n=30),western medicine group(n=30)and blank group(n=30).The patients in all the three groups were treated with basic anti-osteoporosis drugs.The patients in the traditional Chinese medicine group were treated with Erxian decoction after PVP,and those in the western medicine group were treated with celecoxib to relieve pain after operation.The visual analogue(VAS)score,Oswestry dysfunction index(ODI)score,TCM syndrome score and serum indexes such as interleukin-6(IL-6)and estrogen E2 were recorded before treatment and 2 weeks,1 month and 3 months after treatment.[Results](i)In terms of pain relief,the VAS score of the western medicine group was lower than that of the traditional Chinese medicine group after 2 weeks of treatment,but there was no significant difference in VAS score between the two groups after 1 month and 3 months,and the pain improvement of the two groups was better than that of the blank group.(ii)After 3 months of treatment,the ODI score in the traditional Chinese medicine group was lower than that in the western medicine group,and the improvement of TCM syndrome in the traditional Chinese medicine group was better than that in the other two groups 1 and 3 months after treatment(P<0.05).(iii)The level of IL-6 in the western medicine group was lower than that in the other groups after 2 weeks,and there was no significant difference between the two groups after 3 months of treatment.After 3 months of treatment,the level of E2 in the traditional Chinese medicine group was higher than that before treatment and higher than that in the western medicine group and the blank group,but there was no significant difference between the two groups(P>0.05).[Conclusions]Both Erxian decoction and non-steroidal anti-inflammatory drugs can relieve residual low back pain after PVP,and their long-term effects are similar,but Erxian decoction has more advantages in alleviating pain,muscle and joint pain and sensory abnormalities in postmenopausal women.Moreover,it is safe and reliable,and is worthy of clinical application.
基金National Natural Science Foundation of China(No.81973719)Science and technology research project of Liaoning Provincial Department of Education(No.L201921)Liaoning Provincial Science And Technology Plan Project(No.2020JH2/10300068)。
文摘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.
基金2020 National Natural Science Foundation of China(No.82004411)2018 GuangdongProvincial Science and Technology Innovation Strategy Special Funding Project(No.2018A030310508)。
文摘Objective:To explore the mechanism of Erxian Decoction in the treatment of premature ovarian failure.Methods:Based on the method of network pharmacology and molecular docking,the active ingredients of each drug in Erxian Decoction were obtained by searching the TCMSP database;the premature ovarian failure disease targets were collected from the GeneCards,OMIM,PharmGkb and Drugbank databases,and the active ingredients and the disease gene targets were collected Click the intersection to get the predictive target of Erxian Decoction for the treatment of premature ovarian failure.Use Cytoscape 3.8.0 to construct a"drug-component-target-disease"network;construct a protein interaction network(PPI)and streamline the core network through STRING database and Cytoscape;use R Studio software to enrich the Erxiantang treatment POF with GO And KEGG pathway enrichment analysis.Use molecular docking technology to verify the results of the"drug-component-target-disease"network.Results:68 main active ingredients were screened,involving 182 gene targets,among which the main active ingredients include Quercetin,Luteolin,Kaempferol,etc.;The core target genes include RB1,TP53,FOS,CDKN1A,ESR1,AKT1,MAPK1,TNF,etc.;GO enrichment items were obtained,including the 2545 Biological Process(BP),89 Cellular Component(CC),212 Molecular Function(MF);KEGG pathways,including PI3K-Akt signaling pathway,MAPK signaling pathway,and AGE-RAGE signaling pathway in diabetic complications.The verification of the molecular docking results indicated that the main active ingredient has a good binding activity with the core target.Conclusion:This study preliminarily revealed that Erxian Decoction may play a role in the treatment of POF through multi-component,multi-target,and multi-channel synergy,which provides a reference for the next in-depth research.
文摘Objective:This paper aims to explore the mech-anism of Erxian Decoction in treating insoimnia by means of network pharmacology research method.Methods:The com-ponents and related targets of Erxian Decoction are screened by TCMSP database.Disease targets are obtained by OMMM and Gene Cards database,and the common targets of drugs and diseases are obtained.The network diagram of"drug-coumponent-disease-target"is constructed and analyzed.STRING database constructs PPI network and finds the core target.GO and KEGG enrichnent analysis are employed on intersection targets.Results:84 effective components and 169 drug targets.of Erxian Decoction as well as 2614 targets of insomnia are screened out.Seventy-two intersection targets are selected by Venn diagram,and the core targets include IL-6,TNF,VEGFA and L-1β.These intersection targets contain 404 GO processes and 67 KEGG pathways,including TOLL-like receptor signaling pathway,cyclic adenosine monophosphate(CAMP)signaling pathway and tumor necrosis factor(TNF)signaling pathway.Conclusion:Erxian Decoction may play a role in treating insomnia by regulating TOLL-like receptor signaling pathway,cyclic adenosine monophosphate(CAMP)signaling pathway and tumnor necrosis factor(TNF)signaling pathway.
文摘目的:基于网络药理学探讨二仙汤“异病同治”乳腺增生和围绝经期综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选二仙汤中6味中药的活性成分并预测其潜在靶点;通过人类基因数据库(the human gene database,GeneCards)及在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)平台检索乳腺增生和围绝经期综合征的疾病靶点,借助Venn在线工具构建药物与两种疾病的交集靶点。运用Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”网络;利用STRING数据库构建PPI网络,按Dgree值大于等于平均值进一步筛选核心靶点;采用DAVID数据库进行基因本体论(gene ontology,GO)富集分析,同时实现京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果 :根据口服生物利用度(oral bioavailability,OB)≥30%和药物类药性(druglikeness,DL)≥0.18筛选得到二仙汤有效活性成分104个,预测潜在作用靶点147个;通过筛选得到乳腺增生靶点4153个,围绝经期综合征靶点155个,药物与疾病的交集靶点29个,其中IL-6、VEGFA、TNF、TP53、ESR1、CAT、IL-1β等可能是二仙汤治疗乳腺增生和围绝经期综合征的关键靶点。活性成分及靶点主要参与DNA模板转录正调控、基因表达的正调控、胞外间隙、胞外区、类固醇结合、酶结合等;靶基因主要富集在TNF、NOD样体、HIF-1、癌症、PI3K-Akt等信号通路。结论:二仙汤可能通过调控PI3K-Akt、HIF-1等信号通路达到防治乳腺增生和围绝经期综合征的目的。
基金Supported by Liaoning Natural Science Foundation of China(No.2017011854-301)Jinzhou Science and Technology Project,China(No.16B1G35)
文摘Objective:To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction(二仙汤,EXD)as a treatment for premature ovarian failure(POF)using a systems pharmacology approach.Methods:The compounds present in EXD were obtained from three databases.The active ingredient was identified by analyzing the values of oral bioavailability(OB),drug-like ness(DL),and Lipin ski's rule(LR).The active in gredients were further searched in research articles,drug targets in the DrugBank database,and the C-T and T-P networks,as well as by pathway analysis using the Cytoscape platform.Results:A total of 728 compounds were identified in EXD.Of these,59 were identified as active compounds that conformed to the criteria with OB>30%and DL>0.18.By further searches in the literature,126 related targets were ide ntified that could in teract with the active compounds.Additi on ally,it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immline system,modulation of estrogen levels,and anti-oxidative activities,and that it may act in a synergistic or cooperative manner with other therapeutic agents.Conclusions:The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF.The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.
基金Supported by the National Natural Science Foundation of 6hina(No.81904197)Natural Science Foundation of Zhejiang Province(No.LQ15H290002)and 2019 Research and Innovation Fund Project for Young and Middle-aged Researchers of Zhejiang Chinese Medical University(No.KC201944)。
文摘Objective To evaluate the effect of Guilu Erxian Glue(龟鹿二仙胶,GEG)on cyclophosphamide(CTX)-induced bone marrow hematopoietic stem cells(HSCs)senescence in mice and explore the underlying mechanism.Methods The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally(i.p.)with 5×10^6/mL H22 cells per mouse.Fifty tumor-bearing mice were divided into the control,model,pifithrin-α,GEG,and GEG+pifithrin-αgroups using a random number table,10 mice in each group.CTX(100 mg/kg i.p.)was administrated to mice from day 1 to day 3(d1–d3)continuously except for the control group.The mice in the pifithrin-α,GEG and GEG+pifithrin-αgroups were treated with pifithrin-α(2.2 mg/(kg·d)i.p.)for 6 consecutive days(d4–d9),GEG(9.5 g/(kg·d)i.p.)for 9 consecutive days(d1–d9),and GEG plus pifithrin-α,respectively.HSCs were collected after 9-d drug treatment.The anti-aging effect of GEG was studied by cell viability,cell cycle,andβ-galactosidase(β-gal)assays.The mRNA and protein expressions of cyclin-dependent kinase 2(CDK2),CDK4,inhibitor of cyclin-dependent kinase 4a encoding the tumor suppressor protein p16^(p16^INK4a),p21^Cip1/Waf1,p53,and phosphorylated retinoblastoma(pRb)were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot,respectively.Results Compared with the model group,GEG increased cell viability as well as proliferation(P<0.05 or P<0.01)and reducedβ-gal expression.Furthermore,GEG significantly decreased the expressions of p16^INK4a,p53 and p21^Cip1/Waf1 proteins,and increased the expressions of CDK2,CDK4 and pRb proteins compared with the model group(P<0.05 or P<0.01).Conclusion GEG can alleviate CTX-induced HSCs senescence in mice,and the p16^INK4a-Rb signaling pathway might be the underlying mechanism.
文摘Erxian Tang (二仙汤,EXT) is a Chinese herbal formula developed for the treatment of menopausal syndrome in women. In the past 50 years, EXT has shown positive efficacy in the treatment of many chronic diseases in TCM, involving syndrome types of Shen (肾) yin-yang deficiency, yin-deficiency caused yang-flourishing, and disharmony of Chong-Ren meridian. Experimental studies have revealed that EXT has multiple pharmacological actions on such multiple targets as hypothalamus-pituitary-target gland axis, immune function and free radical metabolism, etc.
