Targeting PI3K/Akt/NF-κB and PI3K/Akt/FOXO signaling pathways by Wenshen Qianlie Capsules mitigates testosterone-induced benign prostate hyperplasia in rats

Introduction andObjective.Benign prostatic hyperplasia (BPH) is a prevalent chronic disease in men.In China, Wenshen Qianlie Capsules are usually used for treatment of BPH.The aim of the study is to comprehensively map the targets and pathways of the capsule using network pharmacology, and to validate its efficacy and possible cellular and molecular mechanisms using animal and cellular experiments.Materials and Method.Targets and meridian tropism for the herbs in Capsules were collected from the ETCM 2.0 database.Disease genes were collected from the ETCM 2.0 and Genecards databases.Common genes were subjected to enrichment analysis.Male Wistar rats and human prostatic epithelial/stromal cell lines were induced by testosterone propionate (TP).The prostate weight, body weight, serum dihydrotestosterone (DHT), 5-reductase, and prostate-specific antigen (PSA) in rats were determined.PCNA and caspase-3 in prostate tissue were assayed.Viability, apoptosis, inflammation cytokines, and pathway factors were detected in cells.Results.A total of 516 targets were predicted for the 14 herbs in Capsules.Among them, 90 targets have the potential against BPH.The therapeutic targets were enriched in multiple biological progress and pathways, including PI3K/AKT signaling pathway.Capsules treatment reduced the prostate weight, serum PSA/DHT/5-reductase levels, and prostatic PCNA level, but increased prostatic caspase-3 level.Furthermore, Capsules treatment inhibited the cell viability and inflammatory factors but induced apoptosis of BPH-1 and WPMY-1 cells.Additionally, Capsules treatment decreased the ratios of p-Akt/ Akt, p-I-B/I-B, p-FoxO3a/ FoxO3a, p-NF-B/NF-B, and p-FoxO1/FoxO1.Conclusions.Wenshen Qianlie Capsules may avoid BPH by blocking the activation of PI3K/Akt/NF-B and PI3K/Akt/FOXO signaling pathways.