Perilla Frutescens seed residue extract attenuates testosterone-induced benign prostatic hyperplasia in rats with associated modulation of prostate metabolism and gut microbiota

Benign prostatic hyperplasia (BPH) is a prevalent age-related condition linked to androgen signaling, inflammation, oxidative stress, metabolic dysregulation, and emerging systemic factors, including gut microbiota imbalance. Given the multifactorial nature of BPH pathogenesis, interventions that simultaneously target local prostate alterations and systemic metabolic and microbial disturbances may offer preventive benefits. This study evaluated the protective effects of Perilla frutescens seed residue extract (PCE) in a testosterone propionate (TP)-induced BPH rat model using histological, metabolomic, and gut microbiota profiling. Oral PCE administration for 30 days attenuated TP-induced prostate enlargement, reduced epithelial hyperplasia, and improved prostate histology. At the molecular level, PCE was associated with reduced 5 alpha-reductase expression, lower KLK3 (PSA) accumulation, decreased epithelial proliferation, and suppressed TNF-alpha expression. Untargeted metabolomics revealed PCE-associated remodeling of prostate metabolic pathways, particularly purine metabolism, lipid-related metabolism, as well as oxidative stress responses. PCE also modulated gut microbial composition, increasing selected commensal taxa such as Akkermansia sp. and Turicibacter sp., and improving microbial diversity. Correlation analysis suggested associations between PCE-responsive bacterial genera and prostate metabolites related to purine and amino acid metabolism. Overall, these findings suggest that PCE attenuates TP-induced prostatic hyperplasia through coordinated modulation of local prostate responses, metabolic remodeling, and gut microbial composition. By integrating histological, molecular, metabolomic, and microbiome analyses, this study provides preliminary evidence linking prostate health to host-microbiota interactions and highlights PCE, a value-added product derived from agricultural by-products, as a potential functional food ingredient for BPH prevention and management.