Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by v...Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.展开更多
目的探讨加味瓜蒌瞿麦汤联合米非司酮治疗子宫肌瘤患者的疗效及对其性激素水平的影响。方法选取2020年2月—2022年3月期间于河南省南阳市第二人民医院就诊的痰湿瘀结证子宫肌瘤患者120例,按随机数字表法分为对照组和研究组,每组各60例...目的探讨加味瓜蒌瞿麦汤联合米非司酮治疗子宫肌瘤患者的疗效及对其性激素水平的影响。方法选取2020年2月—2022年3月期间于河南省南阳市第二人民医院就诊的痰湿瘀结证子宫肌瘤患者120例,按随机数字表法分为对照组和研究组,每组各60例。对照组单纯给予米非司酮治疗,研究组在对照组治疗的基础上联合加味瓜蒌瞿麦汤治疗,两组患者均于月经干净开始服药,经期停药,均治疗3个月。观察比较两组患者临床疗效及不良反应发生率,治疗前后月经质量、子宫肌瘤体积及子宫体积,并检测两组患者血清性激素[雌二醇(Estradial,E_(2))、促卵泡生长激素(Folliclestimulating hormone,FSH)、孕酮(Progesterone,P)、促黄体生成素(Luteinizing hormone,LH)]水平。结果治疗后研究组临床总有效率95.00%(57/60)明显高于对照组80.00%(48/60),差异有统计学意义(P<0.05)。治疗后两组患者视觉模拟量表(Visual analog scale,VAS)评分及月经失血图(Pictorial blood loss assessment chart,PBAC)评分均较治疗前降低,差异有统计学意义(P<0.05);且研究组VAS、PBAC评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者子宫肌瘤、子宫体积均较治疗前降低,差异有统计学意义(P<0.05);且研究组子宫肌瘤、子宫体积均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清性激素LH、P、E_(2)及FSH水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组血清性激素LH、P、E_(2)及FSH水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗期间,研究组不良反应发生率10.00%(6/60)与对照组6.67%(4/60)比较,差异无统计学意义(P>0.05)。结论加味瓜蒌瞿麦汤与米非司酮联用能进一步提高子宫肌瘤的疗效,改善月经质量,缩小肌瘤体积,调节性激素水平,具有良好的安全性。展开更多
Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effec...Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.展开更多
基金supported by Weifang Health Commission Traditional Chinese Medicine Research Project Plan(WFZYY2023-1-004).
文摘Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.
文摘目的探讨加味瓜蒌瞿麦汤联合米非司酮治疗子宫肌瘤患者的疗效及对其性激素水平的影响。方法选取2020年2月—2022年3月期间于河南省南阳市第二人民医院就诊的痰湿瘀结证子宫肌瘤患者120例,按随机数字表法分为对照组和研究组,每组各60例。对照组单纯给予米非司酮治疗,研究组在对照组治疗的基础上联合加味瓜蒌瞿麦汤治疗,两组患者均于月经干净开始服药,经期停药,均治疗3个月。观察比较两组患者临床疗效及不良反应发生率,治疗前后月经质量、子宫肌瘤体积及子宫体积,并检测两组患者血清性激素[雌二醇(Estradial,E_(2))、促卵泡生长激素(Folliclestimulating hormone,FSH)、孕酮(Progesterone,P)、促黄体生成素(Luteinizing hormone,LH)]水平。结果治疗后研究组临床总有效率95.00%(57/60)明显高于对照组80.00%(48/60),差异有统计学意义(P<0.05)。治疗后两组患者视觉模拟量表(Visual analog scale,VAS)评分及月经失血图(Pictorial blood loss assessment chart,PBAC)评分均较治疗前降低,差异有统计学意义(P<0.05);且研究组VAS、PBAC评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者子宫肌瘤、子宫体积均较治疗前降低,差异有统计学意义(P<0.05);且研究组子宫肌瘤、子宫体积均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清性激素LH、P、E_(2)及FSH水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组血清性激素LH、P、E_(2)及FSH水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗期间,研究组不良反应发生率10.00%(6/60)与对照组6.67%(4/60)比较,差异无统计学意义(P>0.05)。结论加味瓜蒌瞿麦汤与米非司酮联用能进一步提高子宫肌瘤的疗效,改善月经质量,缩小肌瘤体积,调节性激素水平,具有良好的安全性。
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Provincial Key Laboratory of Tropical Brain Science Research and Transformation Research Project(JCKF2021001)Innovative Research Projects for Graduate Students(HYYS2021B01).
文摘Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.
