A Novel Cultivar 'Wongam' Alleviates Benign Prostatic Hyperplasia 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 deficiency caused by blood stasis, and species (licorice) have long been used to enhance , 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.