Efficacy of Buzhong Yiqi decoction on benign prostatic hyperplasia and its possible mechanism

To explored the mechanism of Buzhong Yigi decoction ( BZYQD) in inhibiting prostatic cell proliferation effect.

The compounds of BZYQD consisted with eight herbs were searched in TCMSP databases and the putative targets of BZYQD were collected in Drugbank database. Then, "Benign prostatic hyperplasia" (BPH) was used to find the targets based on the GeneCards, Online Mendelian Inheritance in Man (OMIM) and Therapeutic Target Database (TTD) databases, and they were further used to collect further collect the intersection targets between BZYQD and BPH by counter-selection. Next, Herb-Compound-Target-Disease network was constructed by Cytoscape software and protein interaction network was built by Search tool for recurring instances of neighbouring genes (STRING) database. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed by Database for Annotation, Visualization and Integrated Discovery (DAVID) database to predict the mechanism of the intersection targets. Mitogen activated protein kinase 8 (MAPK8), interleukin 6 (IL-6) and quercetin were chosen to perform molecular docking. Then 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was to detect the bility of BPH-1 (BPH epithelial cell line) by treated with quercetin at the concentrations of 15, 30, 60, 120 μM for 12, 24, 48, 72 h. The production of IL-6, tumor necrosis factor-α (TNF-α), IL-1β and were mRNA expression detected by enzyme-linked immunosorbent assay kit and quantitative real-time polymerase chain reaction. Western blot was used to detect the expression of phospho-p38 mitogen-activated protein kinase (p-P38) and matrix metalloprotein-9 (MMP-9).

A total 151 chemical ingredients of 8 herbs and 1756 targets in BZYQD, 105 common targets of BZYQD and BPH which mainly involving with MAPK8, IL-6, and so on. GO enrichment analysis got 352 GO entries (0.05) which included 208 entries of biological process, 64 entries of cell component and 80 entries of molecular function. KEGG pathway Enrichment analyses got 20 significant pathways which mainly involved with MAPK signaling way. MTT assay indicated quercetin inhibited the viability of BPH-1 cells by time-and dose-dependent manner. Quercetin decreased the IL-6, TNF-α and IL-1β production and mRNA expression, and the expression of p-P38 and MMP-9 were also obviously reduced after treated with quercetin.

BZYQD inhibited BPH through suppressing inflammatory response which might involving with regulating the MAPK signaling way.