Permixon®, hexane-extracted Serenoa repens, inhibits human prostate and bladder smooth muscle contraction and exerts growth-related functions in human prostate stromal cells

• Published in: Life sciences (1973) Vol. 308; p. 120931
• Main Authors: Tamalunas, Alexander, Wendt, Amin, Springer, Florian, Vigodski, Victor, Ciotkowska, Anna, Rutz, Beata, Wang, Ruixiao, Huang, Ru, Liu, Yuhan, Schulz, Heiko, Ledderose, Stephan, Kolben, Thomas, Magistro, Giuseppe, Stief, Christian G., Hennenberg, Martin
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2022
• Subjects: Lower urinary tract symptoms; Overactive bladder; Phytotherapy; Plant extracts; Prostatic hyperplasia; Smooth muscle contraction; RCT; ATCC; 5-AR; DHT; 7-AAD; OD; CCK-8; Overactive bladder; Phytotherapy; Lower urinary tract symptoms; 5-ARI; WPMY-1; Smooth muscle contraction; LUTS; Plant extracts; OAB; ETB; ETA; APC; EdU; FCS; EAU; Prostatic hyperplasia; BPH; RPMI; HeSr
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120931

Recently, the European Association of Urology recommended hexane-extracted fruit of Serenoa repens (HESr) in their guidelines on management of non-neurogenic male lower urinary tracts symptoms (LUTS). Despite previously lacking recommendations, Permixon® is the most investigated HESr in clinical trials, where it proved effective for male LUTS. In contrast, underlying mechanisms were rarely addressed and are only marginally understood. We therefore investigated effects of Permixon® on human prostate and detrusor smooth muscle contraction and on growth-related functions in prostate stromal cells. Permixon® capsules were dissolved using n-hexane. Contractions of human prostate and detrusor tissues were induced in organ bath. Proliferation (EdU assay), growth (colony formation), apoptosis and cell death (flow cytometry), viability (CCK-8) and actin organization (phalloidin staining) were studied in cultured human prostate stromal cells (WPMY-1). Permixon® inhibited α1-adrenergic and thromboxane-induced contractions in prostate tissues, and methacholine-and thromboxane-induced contractions in detrusor tissues. Endothelin-1-induced contractions were not inhibited. Neurogenic contractions were inhibited in both tissues in a concentration-dependent manner. In WPMY-1 cells, Permixon® caused concentration-dependent breakdown of actin polymerization, inhibited colony formation, reduced cell viability, and proliferation, without showing cytotoxic or pro-apoptotic effects. Our results provide a novel basis that allows, for the first time, to fully explain the ubiquitous beneficial effects of HESr in clinical trials. HESr may inhibit at least neurogenic, α1-adrenergic and thromboxane-induced smooth muscle contraction in the prostate and detrusor, and in parallel, prostate stromal cell growth. Together, this may explain symptom improvements by Permixon® in previous clinical trials. [Display omitted]