To explore the potential mechanism of modified Guizhi Fuling Pill (MGFP) in the treatment of benign prostatic hyperplasia (BPH) by network pharmacology and molecular docking.Then,the BPH model rats were established to verify the key targets from molecular docking.First,the candidate components and target information of plant herbs in MGFP were determined through TCMSP and TCMID databases,while the animal drug Hirudo was determined through relevant literature.Then,the drug-candidate component-target network diagram was constructed using Cytoscape 3.7.1.The potential targets of BPH were determined through GeneCards,OMIM,TTD,DisGeNET and DRUGBANK databases.The intersection targets of components and disease were selected and imported into STRING 11.0 platform,and PPI network diagram was constructed with Bisogenet 3.0.0 plug-in.Subsequently,Metascape platform and KOBAS 3.0 database were used to perform GO functional annotation,KEGG pathway enrichment analysis and network diagram drawing.Then,the core components and key targets with higher degree values in the network diagram were screened,which will be used for molecular docking in AutoDock 4.2.6 and PyMOL 2.2.0 software.Finally,BPH rat model was established by castration combined with subcutaneous injection of testosterone propionate and intragastrical treatment.Then,according to the immunohistochemical results,the expression of BAX in the prostate tissue of rats in each group was observed.The results of network pharmacology analysis showed that a total of 133 candidate components of MGFP were screened out,of which quercetin,β-sitosterol,kaempferol,baicalein,and ellagic acid could act on BPH.The main targets were AKT1,BAX,BCL2,JUN,TGFB1,TNF,IL6,VEGFA and EGFR,which are mainly concentrated in PI3K-AKT signaling pathway and VEGF signaling pathway to participate in the processes of apoptosis,angiogenesis,and inflammation.Molecular docking results showed that all core components and key targets could spontaneously bind,and BAX and β-sitosterol had the strongest binding capacity.Animal experiments showed that compared with the model group,the expression of BAX was significantly increased when the MGFP doses were 6.57,13.14 and 26.28 g/kg (P < 0.01).All these indicated that MGFP might mainly act on the target of BAX to treat BPH.

"> modified Guizhi Fuling Pill, benign prostatic hyperplasia, network pharmacology, molecular docking, mechanism, experimental verification