Objective:To explore the effective components of Huangqi(Astragalus membranaceus(Fisch.)Bge.)and Danshen(Salvia miltiorrhiza Bge.)and predict their potential functional targets,to explore the effect and mechanism of H...Objective:To explore the effective components of Huangqi(Astragalus membranaceus(Fisch.)Bge.)and Danshen(Salvia miltiorrhiza Bge.)and predict their potential functional targets,to explore the effect and mechanism of Huangqi and Danshen ultrafine granule gel on wound vascular healing in rats by network pharmacology and experimental verification.Methods:Using the TCMSP database to screen the active components of two herbs and their potential targets,to search the target related to vascular injury through the Gene Card database,and to select the gene target with correlation coefficient greater than 10%.Then map the disease related target to the potential target of the compound,to obtain the common target,and to import the information to the String online analysis platform and Cytoscape to make the PPI map,and to carry on the topological analysis,KEGG and GO enrichment analysis through Metascape platform.The expression analysis of the main target genes of network pharmacology was verified by pathological section staining and optical density method to determine the content of vascular endothelial growth factor(VEGF)in tissues,the number of tissue new capillaries,and the wound healing rate.Results:A total of 115 active components and 297 target genes were selected from Huangqi and Danshen,and 123 target genes were intersected with vascular injury,among which IL6,AKT1,INS,VEGFA,TNF,EGF,CASP3,MAPK1,TP53 were the active genes with the highest intersection value.The pathways involved are mainly related to AGE-RAGE signaling pathway in diabetic complications,MAPK signaling pathway,Pathways in cancer,human cytomegalovirus infection,Fluid shear stress and atherosclerosis,Endocrine resistance,foxo signaling pathway etc.We experimentally validated VEGFA based on the primary target of vascular regeneration,the experimental results showed that there was different expression of VEGFA proteins in wound vascular healing process,and the quercetin,daidzein,luteolin,apigenin,tanshinone i of 115 active components were selected as the main compounds acting on the VEGFA.Conclusion:This study systematically reveals the material basis and mechanism of Huangqi and Danshen regulating wound vascular healing through multi-component,multi-target and multi-pathway and provides theoretical and scientific basis for the clinical application of Huangqi and Danshen.展开更多
Objective:To study the protective effect of the Mixture of Shengmai Powder and Danshen Decoction(生脉散丹参饮合剂,abbreviated as the Mixture) in the rat model with type 2 diabetic cardiomyopathy (DCM).Methods:Fo...Objective:To study the protective effect of the Mixture of Shengmai Powder and Danshen Decoction(生脉散丹参饮合剂,abbreviated as the Mixture) in the rat model with type 2 diabetic cardiomyopathy (DCM).Methods:Forty-two SD rats with DCM model,established by the combination of insulin resistance by a high-fat diet with the damage of pancreatic islet p cells by intraperitoneal injection of high dose streptozotocin (50 mg/kg) once,were evaluated in the damage of the myocardium by electrocardiogram at the end of 12 weeks of grouping and intervention administration;the extent of damage in the myocardial subcellular structure was observed by electron microscopy;the content of myocardial collagen in the left cardiac ventricle was quantified by Masson staining test;the myocardial cell apoptosis was determined by TUNEL;the changes in the mRNA expression levels of thrombospodin-1(TSP-1) and tribbles homolog 3(TRB-3) by real-time quantitative PCR,the expression levels of myocardial TSP-1,tumor growth factorβ1(TGF-β1),TRB-3,and chymase were detected by immunohistochemistry,and the changes in the expression levels of myocardial TSP-1,active-TGF-β1 (A-TGF-β1) and latent-TGF-β1(L-TGF-β1) protein were tested by Western blotting.Results:Compared with the control group,the myocardial tissue was less damaged,and the extent of damage in the myocardial subcellular structure was less;the collagen fiber content and the cell apoptosis were reduced;the expression levels of TSP-1 mRNA and TRB-3 mRNA,the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and chymase,as well as the average expression levels of the myocardial TSP-1,A-TGFβ1,and L-TGF-β1 protein were decreased in the Mixture group.Conclusion:The Mixture of Shengmai Powder and Danshen Decoction could inhibit the process of myocardial fibrosis in the rat myocardium of DCM through multiple pathways and significantly delay the genesis and progress of DCM in hyperglycemic rats.展开更多
文摘Objective:To explore the effective components of Huangqi(Astragalus membranaceus(Fisch.)Bge.)and Danshen(Salvia miltiorrhiza Bge.)and predict their potential functional targets,to explore the effect and mechanism of Huangqi and Danshen ultrafine granule gel on wound vascular healing in rats by network pharmacology and experimental verification.Methods:Using the TCMSP database to screen the active components of two herbs and their potential targets,to search the target related to vascular injury through the Gene Card database,and to select the gene target with correlation coefficient greater than 10%.Then map the disease related target to the potential target of the compound,to obtain the common target,and to import the information to the String online analysis platform and Cytoscape to make the PPI map,and to carry on the topological analysis,KEGG and GO enrichment analysis through Metascape platform.The expression analysis of the main target genes of network pharmacology was verified by pathological section staining and optical density method to determine the content of vascular endothelial growth factor(VEGF)in tissues,the number of tissue new capillaries,and the wound healing rate.Results:A total of 115 active components and 297 target genes were selected from Huangqi and Danshen,and 123 target genes were intersected with vascular injury,among which IL6,AKT1,INS,VEGFA,TNF,EGF,CASP3,MAPK1,TP53 were the active genes with the highest intersection value.The pathways involved are mainly related to AGE-RAGE signaling pathway in diabetic complications,MAPK signaling pathway,Pathways in cancer,human cytomegalovirus infection,Fluid shear stress and atherosclerosis,Endocrine resistance,foxo signaling pathway etc.We experimentally validated VEGFA based on the primary target of vascular regeneration,the experimental results showed that there was different expression of VEGFA proteins in wound vascular healing process,and the quercetin,daidzein,luteolin,apigenin,tanshinone i of 115 active components were selected as the main compounds acting on the VEGFA.Conclusion:This study systematically reveals the material basis and mechanism of Huangqi and Danshen regulating wound vascular healing through multi-component,multi-target and multi-pathway and provides theoretical and scientific basis for the clinical application of Huangqi and Danshen.
基金Supported by the First Grade of China Postdoctoral Science Foundation(No.20070410129)the Special Fund by China Postdoctoral Science Foundation(No.200801166)+1 种基金the Major Project of Beijing Municipal Science and Technology Committee (No.H020920010330)the Subject of Science and Technology Plan of Beijng Municipal Science and Technology Committee(No.D08050703020802)
文摘Objective:To study the protective effect of the Mixture of Shengmai Powder and Danshen Decoction(生脉散丹参饮合剂,abbreviated as the Mixture) in the rat model with type 2 diabetic cardiomyopathy (DCM).Methods:Forty-two SD rats with DCM model,established by the combination of insulin resistance by a high-fat diet with the damage of pancreatic islet p cells by intraperitoneal injection of high dose streptozotocin (50 mg/kg) once,were evaluated in the damage of the myocardium by electrocardiogram at the end of 12 weeks of grouping and intervention administration;the extent of damage in the myocardial subcellular structure was observed by electron microscopy;the content of myocardial collagen in the left cardiac ventricle was quantified by Masson staining test;the myocardial cell apoptosis was determined by TUNEL;the changes in the mRNA expression levels of thrombospodin-1(TSP-1) and tribbles homolog 3(TRB-3) by real-time quantitative PCR,the expression levels of myocardial TSP-1,tumor growth factorβ1(TGF-β1),TRB-3,and chymase were detected by immunohistochemistry,and the changes in the expression levels of myocardial TSP-1,active-TGF-β1 (A-TGF-β1) and latent-TGF-β1(L-TGF-β1) protein were tested by Western blotting.Results:Compared with the control group,the myocardial tissue was less damaged,and the extent of damage in the myocardial subcellular structure was less;the collagen fiber content and the cell apoptosis were reduced;the expression levels of TSP-1 mRNA and TRB-3 mRNA,the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and chymase,as well as the average expression levels of the myocardial TSP-1,A-TGFβ1,and L-TGF-β1 protein were decreased in the Mixture group.Conclusion:The Mixture of Shengmai Powder and Danshen Decoction could inhibit the process of myocardial fibrosis in the rat myocardium of DCM through multiple pathways and significantly delay the genesis and progress of DCM in hyperglycemic rats.