Formononetin inhibits benign prostatic hyperplasia through estrogen receptors.

The primary objective of this study was to forecast the core targets of formononetin through network pharmacology and to assess its potential anti-benign prostatic hyperplasia (BPH) effects using molecular docking and animal experimentation. Active compounds were filtered from the Swiss ADME database, while drug targets were extrapolated from TTD, GeneCards, and DrugBank databases. Targets overlapping between drug and disease were pinpointed, and PPI networks were subsequently developed. Both GO and KEGG enrichment analyses were executed. The AutodockVina software facilitated molecular docking to examine formononetin's estrogen activity. Mice diagnosed with BPH were grouped into control, TP, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 5 mg/kg + fulvestrant (20 mg/kg/week), and 10 mg/kg + fulvestrant (20 mg/kg/week) groups. Pathological deviations were discerned through H&E and Masson staining. Estrogen receptor and cell cycle gene expressions were quantified by qPCR. Our findings pinpointed 35 potential protein targets bridging formononetin and BPH, with ER-α, EGFR, ER-β, CYP19A1, AChE, and PPARA being the focal targets. The GO and KEGG enrichment analyses indicated that formononetin's targets predominantly revolved around cellular responses to estradiol stimulation, estrogen biosynthesis, steroid hormone receptor activity, steroid binding, and other related processes. These extended to pathways like steroid hormone biosynthesis and estrogen signaling. Molecular docking deduced a stronger affinity of formononetin for ER-β than for ER-α. Examination of pathological sections in formononetin-treated BPH mice demonstrated its significant inhibitory effect on BPH. Concurrently, the estrogen receptor inhibitor, fulvestrant, markedly dampened formononetin's therapeutic efficacy. qPCR assessments revealed that formononetin effectively curtailed ER-β expression within hyperplastic prostate tissues. Moreover, post-formononetin treatment led to a decline in expression levels of cell cycle-related genes, such as CDK1, cyclin A2, CDK2, and cyclin B1. However, this trend was notably stunted with the introduction of an estrogen receptor inhibitor. In summation, through the combined insights of network pharmacology and animal testing, we ascertained that formononetin mitigated cell cycle progression via the estrogen receptor when addressing prostatic hyperplasia. [ABSTRACT FROM AUTHOR]