{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T13:08:13Z","timestamp":1776863293521,"version":"3.51.2"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alexander Von Humboldt Stiftung Foundation Germany","award":["1232056"],"award-info":[{"award-number":["1232056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The roots of Acridocarpus smeathmannii were identified as a natural source of the benzyl-terpene 2-(5-isopropyl-4-methoxy-2-methylbenzyl)phenol (FAH-01, chamanen), which was isolated and structurally characterized by chromatographic and spectroscopic techniques, including two-dimensional NMR analysis. Functionally, FAH-01 exerted pronounced inhibitory effects on human prostate smooth muscle contractility. In organ bath experiments, it reduced noradrenaline-induced contractions by up to 72% and phenylephrine-induced contractions by up to 63%, without affecting agonist potency (pEC50). During electrical field stimulation (2\u201332 Hz), FAH-01 suppressed neurogenic contractile responses, indicating interference with adrenergic and nerve-mediated signaling pathways. Beyond smooth muscle modulation, FAH-01 showed antioxidant activity in the DPPH radical-scavenging assay and exhibited early-stage toxicity in the Artemia salina cysts. Collectively, these findings identify FAH-01 as a bioactive natural product with potent inhibitory effects on adrenergic and neurogenic contraction in human prostate smooth muscle, supporting its therapeutic potential in conditions associated with increased smooth muscle tone. Further preclinical studies are needed to elucidate its mechanisms of action, toxicity, and in vivo efficacy.<\/jats:p>","DOI":"10.3390\/molecules31091380","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:00:32Z","timestamp":1776859232000},"page":"1380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Bioactive Benzyl Terpene from Acridocarpus smeathmannii Inhibits Human Prostate Smooth Muscle Contractility"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2965-1723","authenticated-orcid":false,"given":"Oluwafemi Ezekiel","family":"Kale","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Olabisi Onabanjo University, Ago-Iwoye 120101, Ogun, Nigeria"},{"name":"Bavarian NMR Center (BNMRZ), School of Natural Sciences, Technical University of Munich, 80333 M\u00fcnchen, Germany"},{"name":"Urologische Klinik und Poliklinik LMU Klinikum, LMU M\u00fcnchen, 80539 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1204-8162","authenticated-orcid":false,"given":"Claudia","family":"Huber","sequence":"additional","affiliation":[{"name":"Bavarian NMR Center (BNMRZ), School of Natural Sciences, Technical University of Munich, 80333 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0477-5482","authenticated-orcid":false,"given":"Denis","family":"Schuldeis","sequence":"additional","affiliation":[{"name":"Bavarian NMR Center (BNMRZ), School of Natural Sciences, Technical University of Munich, 80333 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-2262","authenticated-orcid":false,"given":"Alexander","family":"Tamalunas","sequence":"additional","affiliation":[{"name":"Urologische Klinik und Poliklinik LMU Klinikum, LMU M\u00fcnchen, 80539 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hennenberg","sequence":"additional","affiliation":[{"name":"Urologische Klinik und Poliklinik LMU Klinikum, LMU M\u00fcnchen, 80539 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-8279","authenticated-orcid":false,"given":"Wolfgang","family":"Eisenreich","sequence":"additional","affiliation":[{"name":"Bavarian NMR Center (BNMRZ), School of Natural Sciences, Technical University of Munich, 80333 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Narayanankutty, A., Famurewa, A.C., and Oprea, E. (2024). Natural bioactive compounds and human health. Molecules, 29.","DOI":"10.3390\/books978-3-7258-1663-7"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1007\/s00210-024-03622-6","article-title":"Natural products as drug leads: Exploring their potential in drug discovery and development","volume":"398","author":"Singh","year":"2025","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jep.2016.02.032","article-title":"Medicinal plants of Guinea-Bissau: Therapeutic applications, ethnic diversity and knowledge transfer","volume":"183","author":"Catarino","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kale, O.E., Hu, S., Huber, C., Schierholz, F., Ciotkowska, A., Tamalunas, A., Stief, C.G., Eisenreich, W., and Hennenberg, M. (2025). Acridocarpus smeathmannii root extracts inhibit human prostate and bladder smooth muscle contraction, porcine arterial vasoconstriction, and cytotoxicity of prostate stromal cells. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1621346"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kale, O.E., Rauanov, I., Huber, C., Tamalunas, A., Stief, C.G., Eisenreich, W., and Hennenberg, M. (2025). Benzyl Benzoate Isolation from Acridocarpus smeathmannii (DC.) Guill. & Perr Roots and Its Bioactivity on Human Prostate Smooth Muscle Contractions. Pharmaceuticals, 18.","DOI":"10.20944\/preprints202502.2138.v1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/S0031-9422(00)88802-0","article-title":"Aromatic constituents from Uvaria chamae","volume":"16","author":"Lasswell","year":"1977","journal-title":"Phytochemistry"},{"key":"ref_7","first-page":"179","article-title":"3-Isoproyl-9\u03b1-methyl-1, 2, 4a, 9a tetrahydroxanthene, benzyl benzoates and chamanen from Xylopia africana","volume":"1994","author":"Anam","year":"1994","journal-title":"J. Indian Chem. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11570","DOI":"10.1021\/acs.chemrev.7b00287","article-title":"Structural and chemical biology of terpenoid cyclases","volume":"117","author":"Christianson","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/10610278.2023.2260044","article-title":"Terpenoid-based supramolecular materials: Fabrications, performances, applications","volume":"34","author":"Zhang","year":"2023","journal-title":"Supramol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cardoso-Teixeira, A.C., Ferreira-da-Silva, F.W., Peixoto-Neves, D., Oliveira-Abreu, K., Pereira-Gon\u00e7alves, \u00c1., Coelho-de-Souza, A.N., and Leal-Cardoso, J.H. (2018). Hydroxyl group and vasorelaxant effects of perillyl alcohol, carveol, limonene on aorta smooth muscle of rats. Molecules, 23.","DOI":"10.3390\/molecules23061430"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1080\/07391102.2020.1840441","article-title":"Indoloquinoxaline derivatives as promising multi-functional anti-Alzheimer agents","volume":"40","author":"Kanhed","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1021\/acschemneuro.1c00368","article-title":"Scaffold hybridization strategy leads to the discovery of dopamine D3 receptor-selective or multitarget bitopic ligands potentially useful for central nervous system disorders","volume":"12","author":"Bonifazi","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"C\u00e2mara, J.S., Perestrelo, R., Ferreira, R., Berenguer, C.V., Pereira, J.A., and Castilho, P.C. (2024). Plant-derived terpenoids: A plethora of bioactive compounds with several health functions and industrial applications-A comprehensive overview. Molecules, 29.","DOI":"10.3390\/molecules29163861"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1055\/s-2003-45186","article-title":"Antispasmodic effect of the essential oil of Plectranthus barbatus and some major constituents on the guinea-pig ileum","volume":"69","author":"Nascimento","year":"2003","journal-title":"Planta Medica"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Heghes, S.C., Vostinaru, O., Rus, L.M., Mogosan, C., Iuga, C.A., and Filip, L. (2019). Antispasmodic effect of essential oils and their constituents: A review. Molecules, 24.","DOI":"10.3390\/molecules24091675"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1021\/acsbiomedchemau.3c00038","article-title":"N4-substituted piperazinyl norfloxacin derivatives with broad-spectrum activity and multiple mechanisms on gyrase, topoisomerase IV, and bacterial cell wall synthesis","volume":"3","author":"Aboraia","year":"2023","journal-title":"ACS Bio. Med. Chem. Au"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1021\/acsbiomedchemau.5c00058","article-title":"Indole-2-carboxamides Optimization for Antiplasmodial Activity","volume":"5","author":"Kumar","year":"2025","journal-title":"ACS Bio. Med. Chem. Au"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12964-021-00755-6","article-title":"Role of \u03b1-and \u03b2-adrenergic signaling in phenotypic targeting: Significance in benign and malignant urologic disease","volume":"19","author":"Archer","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hennenberg, M., and Michel, M.C. (2023). Adrenoceptors in the lower urinary tract. Adrenoceptors, Springer.","DOI":"10.1007\/164_2023_678"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dai, C., and Khalil, R.A. (2025). Calcium signaling dynamics in vascular cells and their dysregulation in vascular disease. Biomolecules, 15.","DOI":"10.3390\/biom15060892"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3390\/pathophysiology31020018","article-title":"Biophysical mechanisms of vaginal smooth muscle contraction: The role of the membrane potential and ion channels","volume":"31","author":"Mahapatra","year":"2024","journal-title":"Pathophysiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ecoenv.2014.02.022","article-title":"Teratogenic effects and monetary cost of selenium poisoning of fish in Lake Sutton, North Carolina","volume":"104","author":"Lemly","year":"2014","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"200231","DOI":"10.1016\/j.ctmp.2025.200231","article-title":"Ameliorative potential of Acridocarpus smeathmannii extracts on testosterone propionate and sleep deprivation-induced benign prostate hyperplasia rats","volume":"6","author":"Kale","year":"2025","journal-title":"Clin. Tradit. Med. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1124\/jpet.121.001029","article-title":"Inhibition of full smooth muscle contraction in isolated human detrusor tissues by mirabegron is limited to off-target inhibition of neurogenic contractions","volume":"381","author":"Huang","year":"2022","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Baliyan, S., Mukherjee, R., Priyadarshini, A., Vibhuti, A., Gupta, A., Pandey, R.P., and Chang, C.M. (2022). Determination of antioxidants by DPPH radical scavenging activity and quantitative phytochemical analysis of Ficus religiosa. Molecules, 27.","DOI":"10.3390\/molecules27041326"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100082","DOI":"10.1016\/j.toxcx.2021.100082","article-title":"Artemia salina as an animal model for the preliminary evaluation of snake venom-induced toxicity","volume":"12","author":"Okumu","year":"2021","journal-title":"Toxicon X"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.scitotenv.2017.04.183","article-title":"Toxicity of \u03b1-Fe2O3 nanoparticles to Artemia salina cysts and three stages of larvae","volume":"598","author":"Wang","year":"2017","journal-title":"Sci. Total Environ."},{"key":"ref_28","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."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/9\/1380\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:00:45Z","timestamp":1776859245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/9\/1380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":28,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["molecules31091380"],"URL":"https:\/\/doi.org\/10.3390\/molecules31091380","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]}}}