Network pharmacology research and experimental verification of Huangqi(Astragalus Radix)and Jinyingzi(Rosae Laevigatae Fructus)in treating benign prostatic hyperplasia

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.

The Study on the Action Mechanism of the Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)Couplet Herbs on Membranous Nephropathy Based on Network Pharmacology

Objective Our objective was to explore the action mechanism of the Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs in the treatment of membranous nephropathy(MN)based on network pharmacology.Methods The active ingredients and targets of Jinyingzi(Rosae Laevigatae Fructus)and Qianshi(Euryales Semen)were screened by systematic pharmacology database and analysis platform.Online Human Mendelian Genetic database and GeneCards database were used to retrieve MN-related targets.The active ingredient-related targets and MN disease targets were introduced into Venny 2.1,and Wayne diagram was drawn.The intersection targets were the potential targets of the Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs in the treatment of MN.The protein interaction network of potential targets was constructed,and the core targets were screened with String platform.Metascape platform was used for functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG).The“herb-active ingredient-target-pathway”networks were drawn by using Cytoscape software,and the key components,targets,and signaling pathways were screened.Results A total of 8 active ingredients and 193 related targets in Jinyingzi(Rosae Laevigatae Fructus)and Qianshi(Euryales Semen)were screened out;a total of 1,621 targets of MN disease and 105 potential targets for the treatment of MN were obtained in the treatment with Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs;40 core targets were screened by protein–protein interaction network topology analysis;a total of 1,978 results were obtained by GO function enrichment analysis,and 206 signal pathways were obtained by KEGG pathway enrichment analysis and screening.The network topology analysis of“herb-active ingredient-target-pathway”showed that the key components included quercetin,kaempferol,β-sitosterol,etc.;the key targets included protein kinase Bα(AKT),mitogen-activated protein kinase 1(MAPK1),B-cell lymphoma-2(BCL2),prostaglandin-endoperoxide synthase 2(PTGS2),etc.;the key pathways included advanced glycation end product/receptor of AGE signaling pathway,phosphatidyl inositol 3-kinase(PI3K)/AKT signaling pathway,MAPK signaling pathway,hypoxia-inducible factor-1 signaling pathway,Ras signaling pathway,nuclear factor kappa-B(NF-κB)signaling pathway,Toll-like receptors signaling pathway,p53 signaling pathway and vascular endothelial growth factor signaling pathway in the late stage of diabetic complications.Conclusion The Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs can regulate PI3K/AKT,MAPK,NF-κB signaling pathways in MN by targeting proteins of AKT1,MAPK8,PTGS2 through key components of quercetin,β-sitosterol,and kaempferol,so as to inhibit the overexpression of inflammatory factors in renal tissues,regulate inflammatory response,and improve renal function.