{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:55:24Z","timestamp":1791618924208,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013123","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000}}],"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wilhelm Doerenkamp-Foundation","award":["NATVANTAGE RESEARCH GRANT 2018"],"award-info":[{"award-number":["NATVANTAGE RESEARCH GRANT 2018"]}]},{"name":"Wilhem Doerenkamp-Foundation","award":["Natvantage Research Grant 2018"],"award-info":[{"award-number":["Natvantage Research Grant 2018"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Cutaneous leishmaniasis (CL) is caused by <jats:italic>Leishmania<\/jats:italic> parasites and affects 1.2 million cases annually, mainly in the Americas and the Eastern Mediterranean region. The standard treatment with pentavalent antimonials is often limited by its toxicity, prompting the search for alternative therapies. <jats:italic>Arnica montana<\/jats:italic> L. (Asteraceae) is a well-known phytotherapeutic plant with anti-inflammatory properties, traditionally used to treat bruises, sprains, distortions, and inflammation caused by insect bites. In our previous work, Arnica tincture (AT) obtained from the flowers showed excellent in vitro activity against <jats:italic>Leishmania<\/jats:italic> and in vivo activity in a golden hamster model of CL. It also demonstrated high skin permeability and retention in the epidermis without systemic circulation, making it a promising option for topical treatment of CL.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a randomized, open-label, phase Ib-II clinical trial. Adults with parasitologically confirmed uncomplicated CL were randomly assigned to receive AT topically, 3 times daily, for either 30 or 45 days. We assessed therapeutic response and monitored safety by recording adverse events at each follow-up visit. All adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Sixteen subjects were enrolled, with eight assigned to each treatment regimen. Twelve participants completed the 180-day follow-up, all achieved complete lesion healing (100% cure rate). Four participants withdrew their informed consent before or during treatment. The most common adverse events were mild and included erythema, pain, edema, and a burning sensation at the application site. No severe adverse effects were reported.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>AT showed promising results in treating CL and had a favorable safety profile. Due to the small sample size and lack of comparison with standard therapies, further studies with more robust methodologies are needed to confirm these findings.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05094908\" xlink:type=\"simple\">NCT05094908<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0013123","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T17:54:16Z","timestamp":1755539656000},"page":"e0013123","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A phase Ib\/II clinical study to evaluate the safety and efficacy of topical Arnica tincture to treat non-complicated cutaneous leishmaniasis in Colombia"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-4931","authenticated-orcid":true,"given":"Sara M.","family":"Robledo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Quintero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulied","family":"Tabares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Any C.","family":"Garc\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Rios-Echavarria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n D.","family":"V\u00e9lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-9705","authenticated-orcid":true,"given":"Thomas J.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"issue":"2","key":"pntd.0013123.ref001","article-title":"Neglected tropical diseases: a comprehensive review","volume":"16","author":"J Ca","year":"2024","journal-title":"Cureus"},{"issue":"5","key":"pntd.0013123.ref002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"J Alvar","year":"2012","journal-title":"PLoS One"},{"key":"pntd.0013123.ref003","unstructured":"WHO. Leishmaniasis. 2023. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis"},{"key":"pntd.0013123.ref004","doi-asserted-by":"crossref","unstructured":"Organizaci\u00f3n Panamericana de la Salud. Directrices para el tratamiento de las leishmaniasis en la Regi\u00f3n de las Am\u00e9ricas. Segunda edici\u00f3n. Washington, DC: OPS; 2022. Disponible en: https:\/\/doi.org\/10.37774\/9789275325032","DOI":"10.26633\/RPSP.2023.43"},{"issue":"8","key":"pntd.0013123.ref005","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrmicro2608","article-title":"Leishmaniasis: complexity at the host-pathogen interface","volume":"9","author":"P Kaye","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"pntd.0013123.ref006","volume-title":"Control of the leishmaniases: WHO TRS N\u00b0949. Report of a meeting of the WHO Expert Committee on the Control of Leishmaniases","author":"World Health Organization","year":"2010"},{"issue":"6","key":"pntd.0013123.ref007","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s40257-022-00726-8","article-title":"Cutaneous leishmaniasis: a 2022 updated narrative review into diagnosis and management developments","volume":"23","author":"HJC de Vries","year":"2022","journal-title":"Am J Clin Dermatol"},{"issue":"2","key":"pntd.0013123.ref008","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s40121-022-00602-2","article-title":"Treatment of cutaneous leishmaniasis and insights into species-specific responses: a narrative review","volume":"11","author":"RK Madusanka","year":"2022","journal-title":"Infect Dis Ther"},{"issue":"10","key":"pntd.0013123.ref009","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1111\/j.1469-0691.2011.03630.x","article-title":"Leishmaniasis chemotherapy--challenges and opportunities","volume":"17","author":"SL Croft","year":"2011","journal-title":"Clin Microbiol Infect"},{"issue":"2","key":"pntd.0013123.ref010","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1517\/14656566.2015.973850","article-title":"An update on pharmacotherapy for leishmaniasis","volume":"16","author":"S Sundar","year":"2015","journal-title":"Expert Opin Pharmacother"},{"issue":"22","key":"pntd.0013123.ref011","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1056\/NEJMoa021556","article-title":"Oral miltefosine for indian visceral leishmaniasis","volume":"347","author":"S Sundar","year":"2002","journal-title":"N Engl J Med"},{"issue":"11","key":"pntd.0013123.ref012","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1093\/jac\/dks275","article-title":"Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis","volume":"67","author":"TPC Dorlo","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"pntd.0013123.ref013","unstructured":"European Medicines Agency-Community Herbal Monograph on Arnica montana L., Flos. [cited 2025 Apr 3]. Available from: http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Herbal_-_Community_herbal_monograph\/2014\/07\/WC500170007.pdf"},{"key":"pntd.0013123.ref014","first-page":"54","article-title":"Arnicae flos.","volume-title":"Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis","author":"G. Willuhn","year":"2004","edition":"3"},{"key":"pntd.0013123.ref015","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1021\/bk-1998-0691.ch010","article-title":"Arnica flowers: Pharmacology, toxicology, and analysis of the sesquiterpene lactones\u2014their main active substances.","volume-title":"Phytomedicines of Europe\u2014ACS Symposium Series","author":"G. Willuhn","year":"1998"},{"key":"pntd.0013123.ref016","article-title":"Arnica tincture","volume-title":"European Pharmacopoeia","author":"European Directorate for the Quality of Medicines & HealthCare EDQM","year":"2020","edition":"10"},{"issue":"1","key":"pntd.0013123.ref017","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3390\/molecules23010150","article-title":"Arnica Tincture Cures Cutaneous Leishmaniasis in Golden Hamsters","volume":"23","author":"SM Robledo","year":"2018","journal-title":"Molecules"},{"issue":"7","key":"pntd.0013123.ref018","doi-asserted-by":"crossref","first-page":"776","DOI":"10.3390\/ph15070776","article-title":"Therapeutic efficacy of Arnica in hamsters with cutaneous leishmaniasis caused by Leishmania braziliensis and L. tropica","volume":"15","author":"SM Robledo","year":"2022","journal-title":"Pharmaceuticals (Basel)"},{"issue":"4","key":"pntd.0013123.ref019","doi-asserted-by":"crossref","first-page":"742","DOI":"10.3390\/pharmaceutics14040742","article-title":"Dermal absorption of sesquiterpene lactones from Arnica tincture","volume":"14","author":"FM J\u00fcrgens","year":"2022","journal-title":"Pharmaceutics"},{"key":"pntd.0013123.ref020","first-page":"311","volume-title":"Vademecum colombiano de plantas medicinales","author":"Ministerio de la Proteccion Social","year":"2008"},{"issue":"7","key":"pntd.0013123.ref021","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1007\/s00436-017-5454-6","article-title":"Detection and identification of Leishmania spp.: application of two hsp70-based PCR-RFLP protocols to clinical samples from the New World","volume":"116","author":"AM Montalvo","year":"2017","journal-title":"Parasitol Res"},{"issue":"7","key":"pntd.0013123.ref022","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1007\/s10096-011-1463-z","article-title":"Three new sensitive and specific heat-shock protein 70 PCRs for global Leishmania species identification","volume":"31","author":"AM Montalvo","year":"2012","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"pntd.0013123.ref023","unstructured":"Ministerio de Salud y Protecci\u00f3n Social de Colombia. Guidelines for comprehensive clinical care for leishmaniasis in Colombia. 2023. Available from: https:\/\/www.minsalud.gov.co\/sites\/rid\/Lists\/BibliotecaDigital\/RIDE\/VS\/PP\/PAI\/Lineamientos-leishmaniasis.pdf"},{"key":"pntd.0013123.ref024","unstructured":"National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. U.S. Department of Health and Human Services. 2017. Available from: https:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/ctc.htm"},{"issue":"2","key":"pntd.0013123.ref025","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4269\/ajtmh.2010.10-0060","article-title":"Efficacy of miltefosine for the treatment of American cutaneous leishmaniasis","volume":"83","author":"I V\u00e9lez","year":"2010","journal-title":"Am J Trop Med Hyg"},{"issue":"7","key":"pntd.0013123.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0006653","article-title":"A phase II study to evaluate the safety and efficacy of topical 3% amphotericin B cream (Anfoleish) for the treatment of uncomplicated cutaneous leishmaniasis in Colombia","volume":"12","author":"L L\u00f3pez","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"issue":"21","key":"pntd.0013123.ref027","first-page":"3112","article-title":"Effects of Arnica phytotherapeutic and homeopathic formulations on traumatic injuries and inflammatory conditions: a systematic review","volume":"13","author":"C-C Toma","year":"2024","journal-title":"Plants (Basel)"},{"issue":"9","key":"pntd.0013123.ref028","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1515\/bchm.1997.378.9.951","article-title":"Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB","volume":"378","author":"G Lyss","year":"1997","journal-title":"Biol Chem"},{"key":"pntd.0013123.ref029","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4103\/abr.abr_243_23","article-title":"The therapeutic effect of shirvan herbal ointment on human cutaneous leishmaniasis compared with glucantime","volume":"13","author":"M Aghaei","year":"2024","journal-title":"Adv Biomed Res"},{"issue":"2","key":"pntd.0013123.ref030","doi-asserted-by":"crossref","first-page":"100","DOI":"10.4103\/0976-500X.72352","article-title":"CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials","volume":"1","author":"KF Schulz","year":"2010","journal-title":"J Pharmacol Pharmacother"},{"issue":"22","key":"pntd.0013123.ref031","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1001\/jama.2022.21022","article-title":"Guidelines for reporting outcomes in trial reports: The CONSORT-outcomes 2022 extension","volume":"328","author":"NJ Butcher","year":"2022","journal-title":"JAMA"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0013123","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T18:00:03Z","timestamp":1755885603000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013123"}},"subtitle":[],"editor":[{"given":"Sarman","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,18]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0013123","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,18]]}}}