Objective This study aimed to analyze the mechanism of action of Huangqi(Astragalus Radix,HQ)-Jinyingzi(Rosae Laevigatae Fructus,JYZ)in the treatment of benign prostatic hyperplasia(BPH)based on network pharmacology a...Objective This study aimed to analyze the mechanism of action of Huangqi(Astragalus Radix,HQ)-Jinyingzi(Rosae Laevigatae Fructus,JYZ)in the treatment of benign prostatic hyperplasia(BPH)based on network pharmacology and to verify the prediction through animal experimentation.Methods Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM)databases,and literature,the active components and related target genes of HQ and JYZ were screened.The BPH target genes were screened based on the DisGeNET and GeneGards databases,and Excel was used to merge and remove duplicates.The Perl language was used to obtain drug-BPH target genes by intersecting shared target genes.A drug-component-target gene network diagram was constructed using Cytoscape software.The drug-BPH intersection target genes were inputted into the STRING database,and the key target genes were selected according to the degree algorithm.The output formed the basis for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses to determine the potential mechanism of HQ and JYZ in BPH treatment.High,medium,and low doses of HQ and JYZ extract were used to intervene in BPH rats,and then the prostate volume,wet weight,and prostate index of the BPH rats were determined.Changes in prostate histopathology and microvessel density(MVD)were evaluated using immunohistochemistry,and the optimal HQ and JYZ extract dose was confirmed.Finally,the optimal dose was used to intervene in a BPH rat model,and AKT1 and VEGF expressions were examined by immunohistochemistry.Results Based on network pharmacology,33 active components and 772 target genes were identified from HQ and JYZ,along with 817 BPH target genes and 112 drug-BPH common target genes.Among them were 10 key target genes,including AKT1,JUN,MAPK1,IL-6,TNF,ESR1,and VEGFA.KEGG enrichment analysis revealed 135 signaling pathways,including PI3K/AKT,IL-17,TNF,p53,MAPK,VEGF,JAK-STAT,and NF-κB pathways.The animal experiment showed that HQ and JYZ significantly improved prostate volume,wet weight,prostate index,and prostate histopathology of BPH rats,reducing MVD.In addition,HQ and JYZ inhibited the expression of AKT1 and VEGF in the prostate tissue of rats,promoted epithelial cell apoptosis,and inhibited angiogenesis,consistent with the prediction.Conclusion The combination of HQ and JYZ is effective for BPH therapy through multi-compound and multi-target collaboration.Its possible mechanism in treating BPH includes regulation of AKT1,VEGF protein,PI3K/Akt,and VEGF signaling pathways related to apoptosis,angiogenesis,and inflammation,with potential for clinical use and research.展开更多
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
基金We thank for the funding support from the Hunan Provincial Science and Technology Department(No.2020JJ4068 and No.2018SK4012).
文摘Objective This study aimed to analyze the mechanism of action of Huangqi(Astragalus Radix,HQ)-Jinyingzi(Rosae Laevigatae Fructus,JYZ)in the treatment of benign prostatic hyperplasia(BPH)based on network pharmacology and to verify the prediction through animal experimentation.Methods Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM)databases,and literature,the active components and related target genes of HQ and JYZ were screened.The BPH target genes were screened based on the DisGeNET and GeneGards databases,and Excel was used to merge and remove duplicates.The Perl language was used to obtain drug-BPH target genes by intersecting shared target genes.A drug-component-target gene network diagram was constructed using Cytoscape software.The drug-BPH intersection target genes were inputted into the STRING database,and the key target genes were selected according to the degree algorithm.The output formed the basis for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses to determine the potential mechanism of HQ and JYZ in BPH treatment.High,medium,and low doses of HQ and JYZ extract were used to intervene in BPH rats,and then the prostate volume,wet weight,and prostate index of the BPH rats were determined.Changes in prostate histopathology and microvessel density(MVD)were evaluated using immunohistochemistry,and the optimal HQ and JYZ extract dose was confirmed.Finally,the optimal dose was used to intervene in a BPH rat model,and AKT1 and VEGF expressions were examined by immunohistochemistry.Results Based on network pharmacology,33 active components and 772 target genes were identified from HQ and JYZ,along with 817 BPH target genes and 112 drug-BPH common target genes.Among them were 10 key target genes,including AKT1,JUN,MAPK1,IL-6,TNF,ESR1,and VEGFA.KEGG enrichment analysis revealed 135 signaling pathways,including PI3K/AKT,IL-17,TNF,p53,MAPK,VEGF,JAK-STAT,and NF-κB pathways.The animal experiment showed that HQ and JYZ significantly improved prostate volume,wet weight,prostate index,and prostate histopathology of BPH rats,reducing MVD.In addition,HQ and JYZ inhibited the expression of AKT1 and VEGF in the prostate tissue of rats,promoted epithelial cell apoptosis,and inhibited angiogenesis,consistent with the prediction.Conclusion The combination of HQ and JYZ is effective for BPH therapy through multi-compound and multi-target collaboration.Its possible mechanism in treating BPH includes regulation of AKT1,VEGF protein,PI3K/Akt,and VEGF signaling pathways related to apoptosis,angiogenesis,and inflammation,with potential for clinical use and research.
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.
