Counteractive Effects of Diarylpropionitrile on Testosterone-Induced Benign Prostatic Hyperplasia in Rats via Targeting Key Androgenic, Angiogenic, Proliferative, and Inflammatory Mechanisms

Background: Benign prostatic hyperplasia is a common public health problem in aging men across the globe. Diarylpropionitrile, a selective estrogen receptor-beta agonist, favorably regulates cell proliferation and inflammation, two major hallmarks of benign prostatic hyperplasia pathology. Objective: This study aimed to explore the mitigative impact of diarylpropionitrile on testosterone-induced benign prostatic hyperplasia in rats. Methods: =10): a normal control group, a benign prostatic hyperplasia group, a finasteride-treated group, and a diarylpropionitrile-treated group. After 4 weeks of treatment, macroscopic and microscopic features of prostatic hyperplasia and androgenic, proliferative, angiogenic, apoptotic, and inflammatory biomarkers were assessed. Results: Testosterone administration significantly increased prostate weight, prostatic index, and hyperplasia scores. Both diarylpropionitrile and finasteride effectively ameliorated the benign prostatic hyperplasia lesions by reversing these changes. Both treatments significantly lowered elevated prostatic dihydrotestosterone, 5-αR2, β-catenin, and proliferating cell nuclear antigen levels, demonstrating a strong anti-proliferative effect. They also attenuated the increased pro-inflammatory cytokines interleukin-6, interleukin-27, and prostaglandin E2 and growth factors transforming growth factor beta and vascular endothelial growth factor. Furthermore, both agents inhibited testosterone-induced estrogen receptor-beta upregulation, counteracted peroxisome proliferator-activated receptor gamma tissue protein, and boosted the expression of the anti-apoptotic marker B-cell lymphoma 2. Conclusions: Diarylpropionitrile alleviates testosterone-induced benign prostatic hyperplasia in rats by modulating key pathways associated with cellular proliferation and inflammation. Diarylpropionitrile, as an estrogen receptor-beta agonist, represents a promising alternative for the benign prostatic hyperplasia treatment through multi-targeted mechanisms.