Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mecha...Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mechanism is not fully clarified.Method:The active components and potential targets of shenfu decoction were screened by TCMSP database,disease targets of doxorubicin-induced cardiotoxicity were collected by Genecards and OMIM database,and the network diagram of"drug-components-target-disease"was constructed by Cytoscape software.PPI network was constructed by STRING database.The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis.Results:The study found that there are 52 main effective components of shenfu decoction,and 76 genes are involved in the potential therapeutic targets,among which 24 genes are potential targets of shenfu decoction in the treatment of doxorubicin-induced cardiotoxicity.The protein interaction network suggested that BCL2、BAX、CASP9、CASP3、MAPK8 may be the core target.GO enrichment analysis showed 52 cellular biological processes,and enrichment analysis of KEGG pathway revealed 99 involved signaling pathways,including TNF,apoptosis signaling pathways,etc.Conclusion:In this study,the network of"drug-components-target-disease"was constructed through network pharmacology,and it was found that the mechanism of"shenfu decoction"in the treatment of doxorubicin-induced cardiotoxicity involves multiple targets and pathways,which is conducive to guiding clinical medication.展开更多
Objective:The purpose of this thesis is to explore the mechanism of ShenFu Decoction in the treatment of critically ill patients with COVID-19 based on network pharmacology.Methods:The primary active ingredients and p...Objective:The purpose of this thesis is to explore the mechanism of ShenFu Decoction in the treatment of critically ill patients with COVID-19 based on network pharmacology.Methods:The primary active ingredients and potential targets of ShenFu Decoction were searched from the TCMSP database.The targets of COVID-19 were obtained by searching the GeneCards and OMIM databases.A ShenFu Decoction-compound-target-COVID19 network and a protein-protein interaction(PPI)network were respectively constructed through the Cytoscape 3.5.1 software and the STRING database.Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed via Bioconductor bioinformatics software package and R programming language.Results:ShenFu Decoction contains 255 compounds and 94 potential targets.43 primary active ingredients were searched from the TCMSP database with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18 as the retrieval condition.Numbers of targets of COVID-19 were 352 by searching the GeneCards and the OMIM databases.16 key targets were acquired by intersecting the targets of drug with the targets of disease.There were 49 GO terms and 102 pathways after analyzing GO and KEGG.Conclusion:Kaempferol,ginsenoside rh2,beta-sitosterol,Stigmasterol and Deoxy andrographolide might be the main active ingredients which may cause the inhibition of the SARS-CoV-23CL hydrolase activity and regulate ACE2.As a result,the antiviral effect,immunoregulation,targeting cytokine storm of SFD may play an important role in the treatment of critically ill patients with COVID-19 through regulating multiple signaling pathways such as AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,C-type lectin receptor signaling pathway,HIF-1 signaling pathway.展开更多
目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响...目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响。方法BALB/c小鼠经过13.0 Gy剂量的全身照射(total body irradiation,TBI),4 h内经尾静脉注入供鼠骨髓单个核细胞(mononuclear cells,MNCs)8×10^(6)/kg,制作移植小鼠模型,然后随机分为模型组、alloNK组、参附汤组、参附+alloNK组4组,分别给予生理盐水、单用alloNK、单用参附汤和参附汤联合alloNK灌胃,观察治疗前及治疗后第7、14、30天,小鼠外周血象、骨髓NCC、HV及组织病理的变化。结果移植前及移植后第7天各组小鼠外周血象、骨髓NCC、HV无显著性差异。移植后第14天,模型组小鼠白细胞仍处于粒缺期,而单纯alloNK组和参附组小鼠的白细胞均有所上升,参附联合alloNK组小鼠上升幅度高于其他组。移植后第30天,模型组、alloNK组及参附组小鼠白细胞、骨髓NCC、HV均较前回升,但仍低于移植前水平,而参附联合alloNK组小鼠的白细胞、骨髓NCC、HV恢复至移植前水平,与其他组相比差异显著。结论参附汤可保护骨髓免受放射损伤、促进造血功能恢复、缩短粒细胞缺乏时间,而联合alloNK细胞促进造血功能恢复的作用更明显。展开更多
To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and S...To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and SFI. Cell viability, lactate dehydrogenase （LDH） release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 （CYP2J3） mRNA expression were analyzed. RESULTS： The viability of H9c2 cells treated with SFI （37 and 75 mg/mL） was significantly higher than that of H9c2 cells treated with FPI （25 and 50 mg/mL） （P〈0.05, P〈0.01, respectively）. LDH activity of H9c2 cells treated with SFI （75 mg/mL） was significantly decreased （P〈0.01） compared with that of H9c2 cells treated with FPI （50 mg/mL）. SFI （150 mg/mL） significantly attenuated FPI （100 mg/mL）-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI （12 and 25 mg/mL）, SFI （18 and 37 mg/mL） treatment could effectively reverse the change of caspase-3/7 activity （P〈0.01 and P〈0.01, respectively）. Compared with FPI （6 and 25 mg/mL）, apoptotic cells decreased significantly （P〈0.05, P〈0.01, respectively） when H9c2 cells were incubated with SFI （9 and 37 mg/mL）. The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 （P〈0.01）, which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION： These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.展开更多
目的:观察参附强心汤对老年射血分数保留心力衰竭(Heart Failure with Preserved Ejection Fraction,HFpEF)患者中医证候疗效、N末端B型利钠肽原(N-terminal Probrain Natriuretic Peptide,NT-proBNP)、6分钟步行试验(6 Minutes Walk Te...目的:观察参附强心汤对老年射血分数保留心力衰竭(Heart Failure with Preserved Ejection Fraction,HFpEF)患者中医证候疗效、N末端B型利钠肽原(N-terminal Probrain Natriuretic Peptide,NT-proBNP)、6分钟步行试验(6 Minutes Walk Test,6MWT)、明尼苏达心力衰竭生命质量量表(Minnesota Living with Heart Failure Questionnaire,MLHFQ)评分、超声心动图相关指标的影响,进一步明确参附强心汤对该类患者的临床疗效和安全性,为临床治疗此类患者提供新的方向及循证证据。方法:选取老年HFpEF患者116例,将其随机分为两组,对照组采用西医常规治疗,如原发病治疗、利尿、扩血管等,治疗组在对照组基础上加用参附强心汤,对照组和治疗组均治疗12周。观察比较两组中医证候疗效、NT-proBNP、6MWT、心脏超声相关指标[二尖瓣舒张早期血流(E)和舒张晚期血流(A)的比值(E/A)、肺动脉收缩压(PSA)、左房内径(LA)]及MLHFQ评分。结果:两组中医证候疗效、NT-proBNP、6MWT、MLHFQ评分治疗前后组内比较,差异均有统计学意义(P<0.05);治疗后组间比较,中医证候疗效、NT-proBNP、6MWT、MLHFQ评分差异有统计学意义(P<0.05),心脏超声各项指标组间差异有统计学意义(P<0.05)。两组治疗后血常规、肝肾功能、尿常规等未出现异常。结论:在西医治疗基础上加用参附强心汤可进一步改善阳虚水泛型老年HFpEF患者的心功能、运动耐量、生活质量以及预后,且安全性良好。其主要通过温阳利水减轻心脏负荷从而达到改善心功能的作用。但其具体作用机制尚不清楚,需进一步实验研究。展开更多
基金Fund Project:National natural science foundation of China(No.81573915)。
文摘Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mechanism is not fully clarified.Method:The active components and potential targets of shenfu decoction were screened by TCMSP database,disease targets of doxorubicin-induced cardiotoxicity were collected by Genecards and OMIM database,and the network diagram of"drug-components-target-disease"was constructed by Cytoscape software.PPI network was constructed by STRING database.The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis.Results:The study found that there are 52 main effective components of shenfu decoction,and 76 genes are involved in the potential therapeutic targets,among which 24 genes are potential targets of shenfu decoction in the treatment of doxorubicin-induced cardiotoxicity.The protein interaction network suggested that BCL2、BAX、CASP9、CASP3、MAPK8 may be the core target.GO enrichment analysis showed 52 cellular biological processes,and enrichment analysis of KEGG pathway revealed 99 involved signaling pathways,including TNF,apoptosis signaling pathways,etc.Conclusion:In this study,the network of"drug-components-target-disease"was constructed through network pharmacology,and it was found that the mechanism of"shenfu decoction"in the treatment of doxorubicin-induced cardiotoxicity involves multiple targets and pathways,which is conducive to guiding clinical medication.
基金Tan Xieyao and Zhang Huantian traditional Chinese medicine academic inheritance studio in Guangdong Provincial Hospital of TCM(No.E48807)Inheritance studio of Lingnan Cen’s miscellaneous diseases school in Guangdong Provincial Hospital of TCM(No.E43602)
文摘Objective:The purpose of this thesis is to explore the mechanism of ShenFu Decoction in the treatment of critically ill patients with COVID-19 based on network pharmacology.Methods:The primary active ingredients and potential targets of ShenFu Decoction were searched from the TCMSP database.The targets of COVID-19 were obtained by searching the GeneCards and OMIM databases.A ShenFu Decoction-compound-target-COVID19 network and a protein-protein interaction(PPI)network were respectively constructed through the Cytoscape 3.5.1 software and the STRING database.Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed via Bioconductor bioinformatics software package and R programming language.Results:ShenFu Decoction contains 255 compounds and 94 potential targets.43 primary active ingredients were searched from the TCMSP database with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18 as the retrieval condition.Numbers of targets of COVID-19 were 352 by searching the GeneCards and the OMIM databases.16 key targets were acquired by intersecting the targets of drug with the targets of disease.There were 49 GO terms and 102 pathways after analyzing GO and KEGG.Conclusion:Kaempferol,ginsenoside rh2,beta-sitosterol,Stigmasterol and Deoxy andrographolide might be the main active ingredients which may cause the inhibition of the SARS-CoV-23CL hydrolase activity and regulate ACE2.As a result,the antiviral effect,immunoregulation,targeting cytokine storm of SFD may play an important role in the treatment of critically ill patients with COVID-19 through regulating multiple signaling pathways such as AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,C-type lectin receptor signaling pathway,HIF-1 signaling pathway.
文摘目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响。方法BALB/c小鼠经过13.0 Gy剂量的全身照射(total body irradiation,TBI),4 h内经尾静脉注入供鼠骨髓单个核细胞(mononuclear cells,MNCs)8×10^(6)/kg,制作移植小鼠模型,然后随机分为模型组、alloNK组、参附汤组、参附+alloNK组4组,分别给予生理盐水、单用alloNK、单用参附汤和参附汤联合alloNK灌胃,观察治疗前及治疗后第7、14、30天,小鼠外周血象、骨髓NCC、HV及组织病理的变化。结果移植前及移植后第7天各组小鼠外周血象、骨髓NCC、HV无显著性差异。移植后第14天,模型组小鼠白细胞仍处于粒缺期,而单纯alloNK组和参附组小鼠的白细胞均有所上升,参附联合alloNK组小鼠上升幅度高于其他组。移植后第30天,模型组、alloNK组及参附组小鼠白细胞、骨髓NCC、HV均较前回升,但仍低于移植前水平,而参附联合alloNK组小鼠的白细胞、骨髓NCC、HV恢复至移植前水平,与其他组相比差异显著。结论参附汤可保护骨髓免受放射损伤、促进造血功能恢复、缩短粒细胞缺乏时间,而联合alloNK细胞促进造血功能恢复的作用更明显。
基金supported by grants from the National Natural Science Foundation of China(No.81274127,No.81073149)the National Basic Research Program("973 Program")of China(No.2012CB518402,No.2011CB505304)
文摘To evaluate whether Shenfu injection （SFI） protects against cardiac myocyte injury induced by Fupian injection （FPI） in vitro. METHODS： H9c2 cells were separately treated with FPI, Renshen injection （RSI） and SFI. Cell viability, lactate dehydrogenase （LDH） release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 （CYP2J3） mRNA expression were analyzed. RESULTS： The viability of H9c2 cells treated with SFI （37 and 75 mg/mL） was significantly higher than that of H9c2 cells treated with FPI （25 and 50 mg/mL） （P〈0.05, P〈0.01, respectively）. LDH activity of H9c2 cells treated with SFI （75 mg/mL） was significantly decreased （P〈0.01） compared with that of H9c2 cells treated with FPI （50 mg/mL）. SFI （150 mg/mL） significantly attenuated FPI （100 mg/mL）-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI （12 and 25 mg/mL）, SFI （18 and 37 mg/mL） treatment could effectively reverse the change of caspase-3/7 activity （P〈0.01 and P〈0.01, respectively）. Compared with FPI （6 and 25 mg/mL）, apoptotic cells decreased significantly （P〈0.05, P〈0.01, respectively） when H9c2 cells were incubated with SFI （9 and 37 mg/mL）. The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 （P〈0.01）, which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION： These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.
文摘目的:观察参附强心汤对老年射血分数保留心力衰竭(Heart Failure with Preserved Ejection Fraction,HFpEF)患者中医证候疗效、N末端B型利钠肽原(N-terminal Probrain Natriuretic Peptide,NT-proBNP)、6分钟步行试验(6 Minutes Walk Test,6MWT)、明尼苏达心力衰竭生命质量量表(Minnesota Living with Heart Failure Questionnaire,MLHFQ)评分、超声心动图相关指标的影响,进一步明确参附强心汤对该类患者的临床疗效和安全性,为临床治疗此类患者提供新的方向及循证证据。方法:选取老年HFpEF患者116例,将其随机分为两组,对照组采用西医常规治疗,如原发病治疗、利尿、扩血管等,治疗组在对照组基础上加用参附强心汤,对照组和治疗组均治疗12周。观察比较两组中医证候疗效、NT-proBNP、6MWT、心脏超声相关指标[二尖瓣舒张早期血流(E)和舒张晚期血流(A)的比值(E/A)、肺动脉收缩压(PSA)、左房内径(LA)]及MLHFQ评分。结果:两组中医证候疗效、NT-proBNP、6MWT、MLHFQ评分治疗前后组内比较,差异均有统计学意义(P<0.05);治疗后组间比较,中医证候疗效、NT-proBNP、6MWT、MLHFQ评分差异有统计学意义(P<0.05),心脏超声各项指标组间差异有统计学意义(P<0.05)。两组治疗后血常规、肝肾功能、尿常规等未出现异常。结论:在西医治疗基础上加用参附强心汤可进一步改善阳虚水泛型老年HFpEF患者的心功能、运动耐量、生活质量以及预后,且安全性良好。其主要通过温阳利水减轻心脏负荷从而达到改善心功能的作用。但其具体作用机制尚不清楚,需进一步实验研究。
