A Novel Glycyrrhiza korshinskyi Cultivar 'Wongam' Alleviates Benign Prostatic Hyperplasia via G1/S Checkpoint Arrest and Apoptosis: Insights from Network Pharmacology and Experimental Validation.

PURPOSE In traditional Chinese medicine, benign prostatic hyperplasia (BPH) is attributed to qi deficiency caused by blood stasis, and Glycyrrhiza species (licorice) have long been used to enhance qi, relieve congestion, and promote blood circulation. Wongam (WG), a newly developed licorice cultivar generated through hybridization and cultivated in the Republic of Korea, has not yet been evaluated for its anti-BPH properties. This study investigated the pharmacological potential of WG against BPH using an integrated approach combining network pharmacology with experimental validation.

MATERIALS AND METHODS Network pharmacology was applied to identify potential molecular targets and pathways, and the predicted mechanisms were experimentally validated in BPH-1 cells and in rats with testosterone propionate (TP)-induced BPH.

RESULTS WG alleviated prostate enlargement in rats with TP-induced BPH. Network pharmacology predicted that WG could modulate key regulators of cell cycle progression and apoptosis. Consistently, WG suppressed androgen receptor (AR) signaling in both BPH-1 cells and rats with TP-induced BPH. WG also inhibited G1/S checkpoint regulators and induced apoptosis by reducing B-cell lymphoma (Bcl)-2 and Bcl-xL/Bcl-2 associated X protein ratios, leading to the activation of caspase-9 and -3. Through these actions, WG prevented the activation of the AR signaling pathway, promoted cell cycle arrest, and triggered apoptosis, thereby mitigating BPH progression.

CONCLUSIONS These findings, supported by both network pharmacology predictions and experimental data, suggest that WG has promising therapeutic potential for the treatment of BPH.