Natural products for benign prostatic hyperplasia (BPH): structure-activity relationships and pathway mechanisms

Covering: 2012-2025Benign prostatic hyperplasia (BPH) is a prevalent age-related disorder characterized by non-malignant prostate enlargement and lower urinary tract symptoms, arising from the interplay of androgen dysregulation, chronic inflammation, oxidative stress, and stromal remodeling. Natural products and phyto-therapeutics have been extensively investigated as potential therapeutic agents for BPH. However, the literature remains dominated by compound-by-compound descriptions, limiting mechanistic generalization, and structure-guided prioritization. Here, we surveyed studies reported between 2012 and 2025 through a structure-guided, pathway-oriented framework to identify recurring links between chemical features and disease-relevant biological processes. Rather than cataloging individual agents, evidence is organized around major pathogenic axes (AR/5α-reductase-related growth control, inflammatory and redox networks such as NF-κB-Nrf2-NOX, and stroma-epithelium remodeling programs, including TGF-β/Smad and ECM dynamics) and interpreted using motif-level convergence across chemical classes. Across diverse scaffolds, polyphenolic hydroxyl arrays tend to align with inflammation and redox regulation, whereas nitrogen-containing and lipophilic polycyclic frameworks are more frequently associated with endocrine growth signaling and tissue-level remodeling. Importantly, many mechanistic claims rely on downstream biomarkers and are model-dependent, while direct target-engagement evidence remains limited, which constrains molecular-level structure-activity relationship interpretation. By explicitly mapping scaffold motifs to dominant pathogenic axes and highlighting translational gaps driven by pharmacokinetics, standardization, and experimental context, natural products are positioned as privileged starting scaffolds for pathway-directed optimization rather than empirically defined therapeutics.