Preclinical evaluation of waste-derived pomegranate extract (PWE) as a potential preventing and therapeutic agent for benign prostatic hyperplasia.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a highly prevalent age-related condition, affecting nearly half of men over 60 and up to 80% over 80 years old. Chronic inflammation and oxidative stress are recognized contributors to BPH progression and may facilitate the development of prostate cancer. Growing interest in sustainable, natural chemopreventive agents has highlighted agro-industrial by-products as valuable sources of bioactive compounds. METHODS: In this study, we evaluated the protective and therapeutic effects of pomegranate waste extract (PWE), a phytochemical-rich by-product of Mediterranean agri-food processing, in a testosterone-induced rat model of BPH. RESULTS AND DISCUSSION: Immunohistochemistry and Western blot analyses revealed that testosterone administration reduced the expression of PECAM-1 and increased the levels of NRF2, HO-1, and IL1R1, consistently with endothelial dysfunction, oxidative stress, and inflammation. Co-treatment with PWE restored these markers toward control levels, indicating attenuation of testosterone-driven molecular alterations. Proteomic profiling further demonstrated that testosterone dysregulated proteins involved in mitochondrial function, redox balance, and DNA repair; on the contrary, PWE normalized their levels and enhanced antioxidant enzymes. In periprostatic adipose tissue, PWE counteracted testosterone-induced upregulation of HO-1, NRF2, and GPX4. Overall, PWE mitigates oxidative, inflammatory, and metabolic dysfunctions associated with experimental BPH, supporting its potential as a sustainable natural chemopreventive strategy.