Mechanistic Insights Into the Anti-Benign Prostatic Hyperplasia Effect of Licorice Water Extract via p53-Mediated Apoptosis and Cell Cycle Arrest: A Network Pharmacology-Based Experimental Study

Benign prostatic hyperplasia (BPH) is one of the most prevalent nonmalignant diseases in aging men and is accompanied by lower urinary tract symptoms. The sweet-tasting licorice has been widely used as a food additive and medicinal plant with diverse pharmacological effects. Specifically, licorice is known to alleviate prostate swelling and congestion; however, the mechanisms by which licorice exerts beneficial effects on BPH remain poorly understood. Therefore, this study aimed to evaluate the efficacy of licorice water extract (LWE) against BPH and to elucidate its molecular mechanisms. A network pharmacology approach was employed to explore molecular associations between licorice-derived ingredients and BPH-related genes. TP53 (p53) emerged as a central hub gene, with enrichment analyses indicating its involvement in apoptosis and cell cycle regulation. Experimental validation was conducted using human BPH epithelial cell lines and testosterone propionate-induced BPH rats. In both models, LWE inhibited cell proliferation by suppressing activation of the androgen/androgen receptor signaling pathway. Furthermore, LWE induced G1/S cell cycle arrest and apoptosis through regulation of p53. These findings suggest that LWE exerts protective effects against BPH by regulating p53-mediated cell cycle and apoptosis, highlighting its potential as a functional food ingredient for supporting prostate health.