To Explore the Preventive and Therapeutic Effect and Mechanism of Compound Jinqiancao Granules on Benign Prostatic Hyperplasia Based on Network Pharmacology and Experimental Verification
Objective To investigate the preventive and therapeutic effect of Compound Jinqiancao Granules (JQC) on benign prostatic hyperplasia (BPH) and its underlying mechanisms using network pharmacological methods for prediction and animal experiments for verification. Methods (1) The active ingredients of Desmodii Stryracifolii Herba,Plantaginis Herba,Herb of Balt Pyrrosia and Corn Silk were retrieved from TCMSP database,and the literature search was conducted for supplement. The targets of the active ingredients in JQC were screened by using PubChem,Swiss Target Prediction and CTD database. GeneCards,CTD,DRUGBANK and DisGeNET database were used to select BPH-related targets. The potential targets of JQC in treating BPH were obtained through taking the intersection of the targets of the active ingredients in JQC and BPH-related targets. PPI network analysis of potential targets for JQC in treating BPH was performed by using STRING 11.5 database. Metascape platform was used to analyze the GO function and KEGG pathway enrichment of potential targets for JQC in treating BPH. "Drug-ingredients-targets-pathway" network was constructed by using Cytoscape 3.9.1 to predict the key targets for JQC in treating BPH. AutoDock Vina software was used for molecular docking validation between key active ingredients and core targets.(2)A total of 60 male rats were randomly divided into control group,model group,Qianlie Shutong Capsules(0.324 g·kg-1)group,JQC high-,medium-,and low-dose(3.24,1.62,0.81 g·kg-1)groups,with 10 rats in each group. BPH rat model was induced by castration combined with injection of testosterone propionate. The corresponding drug was administered orally once a day for 30 consecutive days. Rat prostate tissue was removed and weighted,then the prostate wet mass index was calculated. The content of COX-2,VEGF and PGE2 in serum was detected by ELISA. HE staining was used to observed pathological changes in rat prostate tissue. The protein expression of AKT1,p-AKT1,PI3K,p-PI3K,COX-2 and VEGF in prostate tissue was measured by Western Blot. Results (1)A total of 260 targets of the active ingredients in JQC,1584 BPH-related targets,and 125 potential targets of JQC in treating BPH were found. PPI results found that AKT1,TNF,TP53,IL1β,EGFR,CASP3 and PTGS2 may be important targets for JQC in treating BPH. The potential targets for JQC in treating BPH are mainly related to IL-17,HIF-1,TNF,and PI3K-AKT pathways. The key active ingredients,such as luteolin,apigenin,plantain asiatica glycoside,mangiferin,shafotaxin and isovitexin,as well as the core targets including PTGS2,AR,CASP3,IL6,PTGS1 and AKT1,were obtained. The molecular binding energies of 24 pairs of "key active ingredients-core targets" were less than or equal to-6 kcal·mol-1. It was found that PTGS2 protein receptor had good binding activity to ligands such as luteolin and apigenin. AKT1 has good affinity with plantain asiatica glycoside,mangiferin,isobutyricin,luteolin,apigenin,shaftaside and isovitexin. (2) Compared with model group,the wet mass and wet mass index of the prostate in JQC high-and medium-dose groups were significantly decreased (P<0.05,P<0.01). Basal cell hyperplasia of the prostate gland in rats was found to be significantly alleviated. The size of the glandular cavity was relatively regular,and the proliferation of epithelial cells had improved. The levels of COX-2,PGE2 and VEGF in the serum were significantly decreased(P<0.05,P<0.01). The protein expression of p-AKT1,p-PI3K,PI3K,COX-2 and VEGF in prostate tissue were significantly down-regulated (P<0.05,P<0.01). Conclusion This study preliminary clarified that JQC has a preventive and therapeutic effect on BPH,and its mechanism is related to active ingredients (plantago asiatica glycoside,mangiferin,and luteolin)-mediated regulation of PI3K-AKT pathway,inhibition of the expression of COX-2,and reduction of PGE2 release,thereby resulting in the down-regulation of VEGF expression and the inhibition of the proliferation of prostate cells.
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维普
