ScholarWorks@중앙대학교

초록

Background and aim Benign prostatic hyperplasia (BPH) involves androgen-driven proliferation with reduced apoptosis. Current 5 alpha-reductase inhibitors can cause adverse effects, motivating safer options. We evaluated whether nobiletin, a polymethoxyflavonoid, mitigates BPH features.Methodology In vitro, nobiletin was applied to BPH-1 epithelial and WPMY-1 stromal cells to assess anti-proliferative effects. In vivo efficacy was tested in a testosterone-induced BPH rat model administered oral nobiletin (1 or 5 mg/kg).Results Nobiletin induced G0/G1 phase cell cycle arrest by suppressing cyclin D1, cyclin E, and cyclin-dependent kinase 2 (CDK2), while elevating p21 and p27 expression. Expression of 5 alpha-reductase, androgen receptor (AR), fibroblast growth factor (FGF), epidermal growth factor (EGF), and B-cell lymphoma 2 (Bcl-2) was reduced, whereas Bcl-2-associated X protein (Bax) was increased. Nobiletin modulated phosphorylation of c-Jun N-terminal kinase (JNK) and p38 and suppression of protein kinase B (AKT) phosphorylation. Nobiletin reduced nuclear factor kappa B (NF-kappa B) DNA-binding activity, which was dependent on JNK and p38. In vivo, nobiletin reduced prostate size, weight, and epithelial thickness, accompanied by molecular markers changing in the same direction as in vitro. Molecular docking analysis further supported the potential of nobiletin to bind 5 alpha-reductase type 2 at the catalytic site.Conclusion These results highlight the potential of nobiletin as a novel therapeutic option for BPH.

키워드