Pine-Extracted Phytosterol β-Sitosterol (APOPROSTAT® Forte) Inhibits Both Human Prostate Smooth Muscle Contraction and Prostate Stromal Cell Growth, Without Cytotoxic Effects: A Mechanistic Link to Clinical Efficacy in LUTS/BPH

<b>Introduction</b>: Medical treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) targets prostate smooth muscle tone for rapid relieve of symptoms and prostate size to prevent disease progression. Recently, EAU guidelines introduced phytomedicines for treatment of LUTS/BPH. Phytosterols may reduce the risk of prostate diseases and seem to be the smallest common denominator between different phytotherapeutic preparations. Thus, we investigated the effects of the highly concentrated phytosterol β-sitosterol on human prostate smooth muscle contraction and cellular functions, including contraction and growth of prostate stromal cells. <b>Materials and Methods</b>: APOPROSTAT^® forte capsules (>70% β-sitosterol, ethanol extract of <i>Pinus pinaster</i>) were dissolved in ethanol. Contractions were induced in human prostate tissues (<i>n</i> = 100) obtained from radical prostatectomy and assessed in organ bath setups. Cytoskeletal organization, proliferation, viability, cytotoxicity, and contraction in stromal cells (WPMY-1) were assessed using phalloidin staining, EdU, colony formation, CCK-8, flow cytometry, and matrix collagen assays. <b>Results</b>: APOPROSTAT^® forte (0.1-30 µg/mL) inhibited adrenergic, non-adrenergic, and neurogenic contractions of human prostate tissues by up to 71%, 69%, and 63%, respectively, in a dose-dependent manner. In WPMY-1 cells, it reduced proliferation and actin organization by up to 67% and 75% after 72 h, without affecting viability or inducing cytotoxicity. Colony formation decreased by up to 60% after 168 h, and contraction in collagen matrix assays was reduced by 57% in a concentration- and time-dependent manner. <b>Conclusions</b>: The natural phytosterol β-sitosterol effectively inhibits both prostate contraction and growth with a favorable safety profile, supporting its beneficial role in LUTS management through phytotherapy.