{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:13:59Z","timestamp":1785921239246,"version":"3.56.0"},"reference-count":74,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Munich Clinician Scientist Program","award":["Reg.-Nr. 047"],"award-info":[{"award-number":["Reg.-Nr. 047"]}]},{"name":"Apogepha Arzneimittel GmbH"},{"name":"Ferdinand Eisenberger-Forschungsstipendium der DGU","award":["TaA1\/FE-21"],"award-info":[{"award-number":["TaA1\/FE-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Introduction: 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 \u03b2-sitosterol on human prostate smooth muscle contraction and cellular functions, including contraction and growth of prostate stromal cells. Materials and Methods: APOPROSTAT\u00ae forte capsules (&gt;70% \u03b2-sitosterol, ethanol extract of Pinus pinaster) were dissolved in ethanol. Contractions were induced in human prostate tissues (n = 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. Results: APOPROSTAT\u00ae forte (0.1\u201330 \u00b5g\/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. Conclusions: The natural phytosterol \u03b2-sitosterol effectively inhibits both prostate contraction and growth with a favorable safety profile, supporting its beneficial role in LUTS management through phytotherapy.<\/jats:p>","DOI":"10.3390\/ph18121864","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:17:36Z","timestamp":1765185456000},"page":"1864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pine-Extracted Phytosterol \u03b2-Sitosterol (APOPROSTAT\u00ae 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"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-2262","authenticated-orcid":false,"given":"Alexander","family":"Tamalunas","sequence":"first","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Schierholz","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Poth","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Vigodski","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brandstetter","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ciotkowska","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Rutz","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3053-944X","authenticated-orcid":false,"given":"Leo Federico","family":"Stadelmeier","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital Munich, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-2088","authenticated-orcid":false,"given":"Stephan","family":"Ledderose","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital Munich, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Rogenhofer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1418-8588","authenticated-orcid":false,"given":"Thomas","family":"Kolben","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3291-9460","authenticated-orcid":false,"given":"Christian Georg","family":"Stief","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hennenberg","sequence":"additional","affiliation":[{"name":"Department of Urology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"ref_1","first-page":"S3","article-title":"Benign prostatic hyperplasia: An overview","volume":"7","author":"Roehrborn","year":"2005","journal-title":"Rev. Urol."},{"key":"ref_2","unstructured":"Gravas, S., Cornu, J.N., Gacci, M., Gratzke, C., Herrmann, T.R.W., Mamoulakis, C., Rieken, M., Speakman, M.J., and Tikkinen, K.A.O. (2021). Management of Non-Neurogenic Male LUTS. EAU Guidelines, European Association of Urology. Edn. Presented at the EAU Annual Congress Milan."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chapple, C. (2011). Overview on the lower urinary tract. Handbook of Experimental Pharmacology, Springer.","DOI":"10.1007\/978-3-642-16499-6_1"},{"key":"ref_4","first-page":"S3","article-title":"Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia","volume":"6","author":"Lepor","year":"2004","journal-title":"Rev. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1038\/ijir.2008.55","article-title":"Pathology of benign prostatic hyperplasia","volume":"20","author":"Roehrborn","year":"2008","journal-title":"Int. J. Impot. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1016\/j.juro.2009.06.047","article-title":"Prostate volume changes over time: Results from the Baltimore Longitudinal Study of Aging","volume":"182","author":"Loeb","year":"2009","journal-title":"J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/j.1464-410X.2010.09993.x","article-title":"Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction","volume":"108","author":"Irwin","year":"2011","journal-title":"BJU Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1749-7922-8-23","article-title":"Quality of life and long-term outcomes of octo- and nonagenarians following acute care surgery: A cross sectional study","volume":"8","author":"Gazala","year":"2013","journal-title":"World J. Emerg. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1007\/s00120-021-01545-1","article-title":"What do urologist do in daily practice? A first \u201cunfiltered\u201d look at patient care","volume":"60","author":"Goebell","year":"2021","journal-title":"Urol. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/nau.22467","article-title":"Prostatic alpha1-adrenoceptors: New concepts of function, regulation, and intracellular signaling","volume":"33","author":"Hennenberg","year":"2014","journal-title":"Neurourol. Urodyn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1517\/14740338.2014.936376","article-title":"Cardiovascular and ocular safety of alpha1-adrenoceptor antagonists in the treatment of male lower urinary tract symptoms","volume":"13","author":"Oelke","year":"2014","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.eururo.2014.11.006","article-title":"Drug Adherence and Clinical Outcomes for Patients Under Pharmacological Therapy for Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia: Population-based Cohort Study","volume":"68","author":"Cindolo","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1080\/13685538.2018.1548589","article-title":"Post-finasteride syndrome\u2014Does it really exist?","volume":"22","author":"Maksym","year":"2019","journal-title":"Aging Male"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1742-1241.2010.02626.x","article-title":"Persistence and adherence in the treatment of overactive bladder syndrome with anticholinergic therapy: A systematic review of the literature","volume":"65","author":"Sexton","year":"2011","journal-title":"Int. J. Clin. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.euf.2016.04.002","article-title":"Efficacy and Safety of Hexanic Lipidosterolic Extract of Serenoa repens (Permixon) in the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: Systematic Review and Meta-analysis of Randomized Controlled Trials","volume":"2","author":"Novara","year":"2016","journal-title":"Eur. Urol. Focus"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1111\/bju.14362","article-title":"Efficacy and safety of a hexanic extract of Serenoa repens (Permixon(R)) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS\/BPH): Systematic review and meta-analysis of randomised controlled trials and observational studies","volume":"122","author":"Alcaraz","year":"2018","journal-title":"BJU Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.2147\/PPA.S484632","article-title":"Phytomedicines in Pharmacotherapy of LUTS\/BPH\u2014What Do Patients Think?","volume":"18","author":"Tamalunas","year":"2024","journal-title":"Patient Prefer. Adherence"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1159\/000517291","article-title":"Choosing a Specialist: An Explanatory Study of Factors Influencing Patients in Choosing a Urologist","volume":"105","author":"Tamalunas","year":"2021","journal-title":"Urol. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BF03189787","article-title":"Distribution study of radioactivity in rats after oral administration of the lipido\/sterolic extract of Serenoa repens (Permixon\u00ae) supplemented with [1-14C]-lauric acid, [1-14C]-oleic acid or [4-14C]-\u03b2-sitosterol","volume":"22","author":"Chevalier","year":"1997","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0306-3623(95)00094-1","article-title":"Mechanisms involved in the spasmolytic effect of extracts from Sabal serrulata fruit on smooth muscle","volume":"27","author":"Gutierrez","year":"1996","journal-title":"Gen. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jep.2013.12.030","article-title":"Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): Effects on rat prostate contractility","volume":"152","author":"Chua","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/1097-0045(20010215)46:3<226::AID-PROS1027>3.0.CO;2-R","article-title":"Do saw palmetto extracts block human alpha1-adrenoceptor subtypes in vivo?","volume":"46","author":"Goepel","year":"2001","journal-title":"Prostate"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/MOU.0b013e3282f0d5c8","article-title":"Plant extracts: Sense or nonsense?","volume":"18","author":"Madersbacher","year":"2008","journal-title":"Curr. Opin. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"120931","DOI":"10.1016\/j.lfs.2022.120931","article-title":"Permixon\u00ae, hexane-extracted Serenoa repens, inhibits human prostate and bladder smooth muscle contraction and exerts growth-related functions in human prostate stromal cells","volume":"308","author":"Tamalunas","year":"2022","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.3390\/nu5093617","article-title":"Fatty acid and phytosterol content of commercial saw palmetto supplements","volume":"5","author":"Penugonda","year":"2013","journal-title":"Nutrients"},{"key":"ref_26","first-page":"467","article-title":"The use of beta-sitosterol for the treatment of prostate cancer and benign prostatic hyperplasia","volume":"11","author":"Macoska","year":"2023","journal-title":"Am. J. Clin. Exp. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1046\/j.1464-410X.1997.t01-1-00362.x","article-title":"A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto Study group","volume":"80","author":"Klippel","year":"1997","journal-title":"Br. J. Urol."},{"key":"ref_28","first-page":"12","article-title":"Konservative Therapie der benignen Prostatahyperplasie mit hochdosiertem \u00df-Sitosterin (65 mg)","volume":"1\/93","author":"Fischer","year":"1993","journal-title":"UROSCOP"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/S0140-6736(95)91085-9","article-title":"Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group","volume":"345","author":"Berges","year":"1995","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/sj.pcan.4500746","article-title":"Not all brands are created equal: A comparison of selected components of different brands of Serenoa repens extract","volume":"7","author":"Habib","year":"2004","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bu\u021b, M.G., J\u00eetc\u0103, G., Imre, S., Vari, C.E., \u0150sz, B.E., J\u00eetc\u0103, C.M., and Tero-Vescan, A. (2023). The Lack of Standardization and Pharmacological Effect Limits the Potential Clinical Usefulness of Phytosterols in Benign Prostatic Hyperplasia. Plants, 12.","DOI":"10.3390\/plants12081722"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1046\/j.1464-410x.1999.00026.x","article-title":"beta-sitosterol for the treatment of benign prostatic hyperplasia: A systematic review","volume":"83","author":"Wilt","year":"1999","journal-title":"BJU Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4728","DOI":"10.1021\/jf050262q","article-title":"Procyanidin fractions from pine (Pinus pinaster) bark: Radical scavenging power in solution, antioxidant activity in emulsion, and antiproliferative effect in melanoma cells","volume":"53","author":"Selga","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4081\/aiua.2019.3.139","article-title":"Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer","volume":"91","author":"Cicero","year":"2019","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/pros.23293","article-title":"Non-Adrenergic, Tamsulosin-Insensitive Smooth Muscle Contraction is Sufficient to Replace alpha1-Adrenergic Tension in the Human Prostate","volume":"77","author":"Hennenberg","year":"2017","journal-title":"Prostate"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"But, M.G., Tero-Vescan, A., Puscas, A., Jitca, G., and Marc, G. (2024). Exploring the Inhibitory Potential of Phytosterols beta-Sitosterol, Stigmasterol, and Campesterol on 5-Alpha Reductase Activity in the Human Prostate: An In Vitro and In Silico Approach. Plants, 13.","DOI":"10.3390\/plants13223146"},{"key":"ref_37","first-page":"e60309","article-title":"Assessing beta-Sitosterol Levels in Dietary Supplements for Benign Prostatic Hyperplasia: Implications for Therapeutic Efficacy","volume":"16","author":"Imre","year":"2024","journal-title":"Cureus"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sudeep, H.V., Venkatakrishna, K., Amrutharaj, B., and Shyamprasad, K. (2019). A phytosterol-enriched saw palmetto supercritical CO2 extract ameliorates testosterone-induced benign prostatic hyperplasia by regulating the inflammatory and apoptotic proteins in a rat model. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2697-z"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00210-020-02044-4","article-title":"Purinergic smooth muscle contractions in the human prostate: Estimation of relevance and characterization of different agonists","volume":"394","author":"Spek","year":"2021","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"F47","DOI":"10.1152\/ajprenal.00125.2017","article-title":"Inhibition of smooth muscle contraction and ARF6 activity by the inhibitor for cytohesin GEFs, secinH3, in the human prostate","volume":"314","author":"Herlemann","year":"2018","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"172985","DOI":"10.1016\/j.ejphar.2020.172985","article-title":"Onvansertib, a polo-like kinase 1 inhibitor, inhibits prostate stromal cell growth and prostate smooth muscle contraction, which is additive to inhibition by alpha1-blockers","volume":"873","author":"Wang","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Aguirre-Crespo, F.J., Arag\u00f3n-Gast\u00e9lum, J.L., Guti\u00e9rrez-Alc\u00e1ntara, E.J., Zamora-Crescencio, P., G\u00f3mez-Galicia, D.L., Alatriste-Kurzel, D.R., Alvarez, G., and Hern\u00e1ndez-N\u00fa\u00f1ez, E. (2024). \u03b2-Sitosterol Mediates Gastrointestinal Smooth Muscle Relaxation Induced by Coccoloba uvifera via Muscarinic Acetylcholine Receptor Subtype 3. Sci. Pharm., 92.","DOI":"10.3390\/scipharm92020019"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/cvr\/cvs370","article-title":"\u03b2-Sitosterol oxidation products attenuate vasorelaxation by increasing reactive oxygen species and cyclooxygenase-2","volume":"97","author":"Yang","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1177\/1933719109352687","article-title":"The effects of pomegranate seed extract and beta-sitosterol on rat uterine contractions","volume":"17","author":"Promprom","year":"2010","journal-title":"Reprod. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"156030","DOI":"10.1016\/j.phymed.2024.156030","article-title":"beta-sitosterol alleviates pulmonary arterial hypertension by altering smooth muscle cell phenotype and DNA damage\/cGAS\/STING signaling","volume":"135","author":"Li","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1046\/j.1464-410x.2000.00672.x","article-title":"Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: An 18-month follow-up","volume":"85","author":"Berges","year":"2000","journal-title":"BJU Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1016\/S0022-5347(01)66780-6","article-title":"Benign prostatic hyperplasia specific health status measures in clinical research: How much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients?","volume":"154","author":"Barry","year":"1995","journal-title":"J. Urol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1056\/NEJMoa030656","article-title":"The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia","volume":"349","author":"McConnell","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.eururo.2009.09.035","article-title":"The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study","volume":"57","author":"Roehrborn","year":"2010","journal-title":"Eur. Urol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Alcaraz, A., Rodriguez-Antolin, A., Carballido-Rodriguez, J., Castro-Diaz, D., Medina-Polo, J., Fernandez-Gomez, J.M., Ficarra, V., Palou, J., de Leon Roca, J.P., and Angulo, J.C. (2021). Efficacy and tolerability of the hexanic extract of Serenoa repens compared to tamsulosin in moderate-severe LUTS-BPH patients. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-98586-5"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0022-4731(84)90264-4","article-title":"Inhibition of androgen metabolism and binding by a liposterolic extract of \u201cSerenoa repens B\u201d in human foreskin fibroblasts","volume":"20","author":"Sultan","year":"1984","journal-title":"J. Steroid Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/(SICI)1097-0045(19990901)40:4<232::AID-PROS4>3.0.CO;2-0","article-title":"Serenoa repens (Permixon): A 5alpha-reductase types I and II inhibitor-new evidence in a coculture model of BPH","volume":"40","author":"Bayne","year":"1999","journal-title":"Prostate"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0303-7207(95)03526-D","article-title":"5 alpha-Reductase type 1 is localized to the outer nuclear membrane","volume":"110","author":"Savory","year":"1995","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0960-0760(91)90403-R","article-title":"Partial purification of human prostatic 5 alpha-reductase (3-oxo-5 alpha-steroid:NADP+ 4-ene-oxido-reductase; EC 1.3.1.22) in a stable and active form","volume":"38","author":"Sargent","year":"1991","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.clinthera.2007.01.018","article-title":"A review of the clinical efficacy and safety of 5alpha-reductase inhibitors for the enlarged prostate","volume":"29","author":"Naslund","year":"2007","journal-title":"Clin. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1089\/107555302317371433","article-title":"A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia","volume":"8","author":"Prager","year":"2002","journal-title":"J. Altern. Complement. Med."},{"key":"ref_57","first-page":"153","article-title":"Effect of beta-sitosterol as inhibitor of 5 alpha-reductase in hamster prostate","volume":"46","author":"Cabeza","year":"2003","journal-title":"Proc. West. Pharmacol. Soc."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Khan, Z., Nath, N., Rauf, A., Emran, T.B., Mitra, S., Islam, F., Chandran, D., Barua, J., Khandaker, M.U., and Idris, A.M. (2022). Multifunctional roles and pharmacological potential of beta-sitosterol: Emerging evidence toward clinical applications. Chem. Biol. Interact., 365.","DOI":"10.1016\/j.cbi.2022.110117"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bao, X., Zhang, Y., Zhang, H., and Xia, L. (2022). Molecular Mechanism of beta-Sitosterol and its Derivatives in Tumor Progression. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.926975"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/00008469-200608000-00009","article-title":"In-vitro effects of polyphenols from cocoa and beta-sitosterol on the growth of human prostate cancer and normal cells","volume":"15","author":"Jourdain","year":"2006","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1159\/000020227","article-title":"Effect of beta-sitosterol on transforming growth factor-beta-1 expression and translocation protein kinase C alpha in human prostate stromal cells in vitro","volume":"37","author":"Kassen","year":"2000","journal-title":"Eur. Urol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0092-8674(90)90155-8","article-title":"TGF-beta stimulation and inhibition of cell proliferation: New mechanistic insights","volume":"63","author":"Moses","year":"1990","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/path.2077","article-title":"The ageing male reproductive tract","volume":"211","author":"Sampson","year":"2007","journal-title":"J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1083\/jcb.200412015","article-title":"TGF-\u03b2 maintains dormancy of prostatic stem cells in the proximal region of ducts","volume":"170","author":"Salm","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1097\/01.ju.0000140503.11467.8e","article-title":"Is there a scientific basis for the therapeutic effects of serenoa repens in benign prostatic hyperplasia? Mechanisms of action","volume":"172","author":"Buck","year":"2004","journal-title":"J. Urol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1159\/000019570","article-title":"Effect of the lipidosterolic extract of Serenoa repens (Permixon) and its major components on basic fibroblast growth factor-induced proliferation of cultures of human prostate biopsies","volume":"33","author":"Cousse","year":"1998","journal-title":"Eur. Urol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00204-020-02669-7","article-title":"In vitro prediction of organ toxicity: The challenges of scaling and secondary mechanisms of toxicity","volume":"94","author":"Hengstler","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"119771","DOI":"10.1016\/j.lfs.2021.119771","article-title":"Lenalidomide and pomalidomide inhibit growth of prostate stromal cells and human prostate smooth muscle contraction","volume":"281","author":"Tamalunas","year":"2021","journal-title":"Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tamalunas, A., Wendt, A., Springer, F., Vigodski, V., Trieb, F., Eitelberger, N., Poth, H., Ciotkowska, A., Rutz, B., and Hu, S. (2022). Inhibition of Human Prostate and Bladder Smooth Muscle Contraction, Vasoconstriction of Porcine Renal and Coronary Arteries, and Growth-Related Functions of Prostate Stromal Cells by Presumed Small Molecule G\u03b1q\/11 Inhibitor, YM-254890. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.884057"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Tamalunas, A., Wendt, A., Springer, F., Vigodski, V., Trieb, M., and Eitelberger, N. (2024). Immunomodulatory imide drugs inhibit human detrusor smooth muscle contraction and growth of human detrusor smooth muscle cells, and exhibit vaso-regulatory functions. Biomed. Pharmacother., 177.","DOI":"10.1016\/j.biopha.2024.117066"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e23604","DOI":"10.1096\/fj.202400362R","article-title":"Isoform-independent promotion of contractility and proliferation, and suppression of survival by with no lysine\/K kinases in prostate stromal cells","volume":"38","author":"Liu","year":"2024","journal-title":"FASEB J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1093\/bioinformatics\/btu575","article-title":"Cell population identification using fluorescence-minus-one controls with a one-class classifying algorithm","volume":"30","author":"Feher","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1124\/mol.119.118927","article-title":"New Author Guidelines for Displaying Data and Reporting Data Analysis and Statistical Methods in Experimental Biology","volume":"97","author":"Michel","year":"2020","journal-title":"Mol. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/bph.14153","article-title":"Experimental design and analysis and their reporting II: Updated and simplified guidance for authors and peer reviewers","volume":"175","author":"Curtis","year":"2018","journal-title":"Br. J. Pharmacol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1864\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:18:59Z","timestamp":1765185539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,6]]},"references-count":74,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ph18121864"],"URL":"https:\/\/doi.org\/10.3390\/ph18121864","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,6]]}}}