Therapeutic potential of Diosmin against benign prostatic hyperplasia via regulation of androgen receptor and NF-κB signaling

Benign prostatic hyperplasia (BPH) is a prevalent benign enlargement of the prostate driven by androgen receptor (AR) signaling, oxidative stress, and chronic inflammation, and although current therapies target androgen metabolism, their adverse effects underscore the need for safer, naturally derived alternatives. In this study, the therapeutic potential of Diosmin, a natural flavonoid glycoside having antioxidant and anti-inflammatory properties, was evaluated in a testosterone-propionate (TP: 5 mg/kg)-induced BPH model in male Wistar rats. Diosmin (40 and 80 mg/kg) significantly attenuated prostate enlargement, reflected by reduced serum prostate-specific antigen (PSA) and dihydrotestosterone (DHT), and enhanced antioxidant defenses by increasing catalase (CAT), glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), and glutathione peroxidase (GPx), while lowering malondialdehyde (MDA) levels. Mechanistic analysis revealed that Diosmin downregulated AR, steroid 5α-reductase type 2 (SRD5A2), and urokinase plasminogen activator receptor (uPAR), concurrently suppressing inflammatory mediators including NF-κB, IL-6, COX-2, TNF-α, IL-1β, and TGF-β1. It further restored apoptotic balance by upregulating Bax and decreasing Bcl-2 expression. Histopathological observations corroborated these findings by demonstrating preserved glandular architecture and reduced stromal hyperplasia. Overall, the findings suggest that Diosmin may attenuate TP-induced BPH, possibly through regulation of AR- and NF-κB–associated pathways, enhancement of antioxidant defenses, and modulation of apoptotic balance. These results highlight Diosmin as a promising naturally derived candidate for further investigation in the management of BPH.