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
Chemomics is an interdisciplinary study using approaches from chemoinformatics,bioinformatics,synthetic chemistry,and other related disciplines.Biological systems make natural products from endogenous small molecules ...Chemomics is an interdisciplinary study using approaches from chemoinformatics,bioinformatics,synthetic chemistry,and other related disciplines.Biological systems make natural products from endogenous small molecules (natural product building blocks) through a sequence of enzyme catalytic reactions.For each reaction,the natural product building blocks may contribute a group of atoms to the target natural product.We describe this group of atoms as a chemoyl.A chemome is the complete set of chemoyls in an organism.Chemomics studies chemomes and the principles of natural product syntheses and evolutions.Driven by survival and reproductive demands,biological systems have developed effective protocols to synthesize natural products in order to respond to environmental changes;this results in biological and chemical diversity.In recent years,it has been realized that one of the bottlenecks in drug discovery is the lack of chemical resources for drug screening.Chemomics may solve this problem by revealing the rules governing the creation of chemical diversity in biological systems,and by developing biomimetic synthesis approaches to make quasi natural product libraries for drug screening.This treatise introduces chemomics and outlines its contents and potential applications in the fields of drug innovation.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.
基金supported by the National Science and Technology Major Project of China (2010ZX09102-305)the National High-tech R&D Program of China (863 Program,2012AA020307)+1 种基金the Introduction of Innovative R&D Team Program of Guangdong Province (2009010058)the National Natural Science Foundation of China (81173470)
文摘Chemomics is an interdisciplinary study using approaches from chemoinformatics,bioinformatics,synthetic chemistry,and other related disciplines.Biological systems make natural products from endogenous small molecules (natural product building blocks) through a sequence of enzyme catalytic reactions.For each reaction,the natural product building blocks may contribute a group of atoms to the target natural product.We describe this group of atoms as a chemoyl.A chemome is the complete set of chemoyls in an organism.Chemomics studies chemomes and the principles of natural product syntheses and evolutions.Driven by survival and reproductive demands,biological systems have developed effective protocols to synthesize natural products in order to respond to environmental changes;this results in biological and chemical diversity.In recent years,it has been realized that one of the bottlenecks in drug discovery is the lack of chemical resources for drug screening.Chemomics may solve this problem by revealing the rules governing the creation of chemical diversity in biological systems,and by developing biomimetic synthesis approaches to make quasi natural product libraries for drug screening.This treatise introduces chemomics and outlines its contents and potential applications in the fields of drug innovation.
