{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T23:11:42Z","timestamp":1760569902650,"version":"build-2065373602"},"reference-count":41,"publisher":"Georg Thieme Verlag KG","issue":"13","funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005667","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa e Inova\u00e7\u00e3o do Estado de Santa Catarina","doi-asserted-by":"crossref","award":["14768"],"award-info":[{"award-number":["14768"]}],"id":[{"id":"10.13039\/501100005667","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["420084\/2018-5"],"award-info":[{"award-number":["420084\/2018-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Psoriasis patients often discontinue oral and injectable treatments due to concerns about both safety and efficacy. Issues such as adverse side effects, limited long-term effectiveness, and fear of potential complications contribute to non-adherence, impacting treatment outcomes and patients\u02bc quality of life. Betulinic acid (BA) forms supramolecular aggregates through self-assembly in a hydroalcoholic vehicle, which was hypothesized to have antipsoriatic activity when applied topically. To test this, imiquimod was applied to induce psoriasis-like skin inflammation in mice (except in the untreated group) every 24 hours for 5 days. Two hours after each imiquimod application, the groups received either 100\u2009\u00b5L of vehicle (10% glycerol aqueous solution), 0.05\u2009mg\/mL clobetasol (Clo), or 0.5\u2009mg\/mL BA. At the end of the study, the Psoriasis Area and Severity Index (PASI) was evaluated (n\u2009=\u200912\/group), and complete skin clearance time (CSC) was determined in six mice per group. The\n          remaining six mice per group were used to assess acanthosis, lymphocyte and granulocyte infiltration, and Akt and ERK phosphorylation in skin samples, as well as TNF\u03b1, IL-17A, IFN\u03b3, and TGF\u03b2 levels in serum. To assess treatment safety, we evaluated food and water intake, ambulation pattern, body weight gain, organ weights, and blood parameters. BA significantly reduced CSC time by up to 40% compared to the control and was 10% faster than Clo. Both BA and Clo reduced PASI and acanthosis to approximately one-third of control values, normalized immune cell infiltration and TNF\u03b1 levels, decreased IL-17A by more than 30%, and reduced p-Akt and p-ERK2. BA uniquely normalized IFN\u03b3 levels without causing intolerable toxicity. Using an animal model of psoriatic skin inflammation, our findings support BA as a strong candidate for clinical translation, warranting further studies on its safety, pharmacokinetics, and optimal dosage in humans, potentially\n          leading to randomized controlled trials in psoriasis patients.<\/jats:p>","DOI":"10.1055\/a-2644-8732","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T19:21:52Z","timestamp":1751052112000},"page":"771-780","source":"Crossref","is-referenced-by-count":0,"title":["Local and Systemic Effects of Topical Betulinic Acid in a Psoriasis-like Inflammation Model in Mice"],"prefix":"10.1055","volume":"91","author":[{"given":"Fl\u00e1via S.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Universidade do Sul de Santa Catarina, Palho\u00e7a, SC, Brazil"},{"name":"Instituto Federal Catarinense, Cambori\u00fa, SC, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo S.","family":"Silva","sequence":"additional","affiliation":[{"name":"Universidade do Sul de Santa Catarina, Palho\u00e7a, SC, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael V.","family":"Soares","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Centro de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Santa Catarina \u2013 UFSC, Florian\u00f3polis, SC, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Ourique","sequence":"additional","affiliation":[{"name":"Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziane L.D.R.","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Citovet Veterinary Histopathology Laboratory, Florian\u00f3polis, SC, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel F.","family":"Martins","sequence":"additional","affiliation":[{"name":"Universidade do Sul de Santa Catarina, Palho\u00e7a, SC, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2844-8563","authenticated-orcid":false,"given":"Ariane","family":"Zamoner","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Centro de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Santa Catarina \u2013 UFSC, Florian\u00f3polis, SC, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-4040","authenticated-orcid":false,"given":"Maicon R.","family":"Kviecinski","sequence":"additional","affiliation":[{"name":"Universidade do Sul de Santa Catarina, Palho\u00e7a, SC, Brazil"},{"name":"Departamento de Bioqu\u00edmica, Centro de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Santa Catarina \u2013 UFSC, Florian\u00f3polis, SC, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref1","first-page":"5","volume-title":"Global Report on Psoriasis","author":"World Health Organization (WHO)","year":"2016"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.jaad.2013.12.018","article-title":"Patient perspectives in the management of psoriasis: Results from the population-based multinational assessment of psoriasis and psoriatic arthritis survey","volume":"70","author":"M G Lebwohl","year":"2014","journal-title":"J Am Acad Dermatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"13313","DOI":"10.3390\/ijms241713313","article-title":"Challenges and future trends in the treatment of psoriasis","volume":"24","author":"H J Lee","year":"2023","journal-title":"Int J Mol 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Immunopharmacol"},{"key":"ref10","first-page":"22","article-title":"Topical corticosteroid therapy for psoriasis-a review of clobetasol propionate 0.025\u200a% cream and the clinical relevance of penetration modification","volume":"13","author":"J Q Del Rosso","year":"2020","journal-title":"J Clin Aesthet Dermatol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"5836","DOI":"10.4049\/jimmunol.0802999","article-title":"Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23\/IL-17 Axis","volume":"182","author":"L van der Fits","year":"2009","journal-title":"J Immunol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.jep.2016.12.046","article-title":"Anti-psoriatic potential of Solanum xanthocarpum stem in Imiquimod-induced psoriatic mice model","volume":"198","author":"K M Parmar","year":"2017","journal-title":"J 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Pavlova","year":"2003","journal-title":"Fitoterapia"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.molmed.2004.11.001","article-title":"Betulinic acid derivatives as HIV-1 antivirals","volume":"11","author":"C Aiken","year":"2005","journal-title":"Trends Mol Med"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"883857","DOI":"10.3389\/fphar.2022.883857","article-title":"Anti-inflammatory activities of betulinic acid: A review","volume":"13","author":"J F Oliveira-Costa","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.abb.2018.04.015","article-title":"The potent insulin secretagogue effect of betulinic acid is mediated by potassium and chloride channels","volume":"648","author":"A J Gomes Castro","year":"2018","journal-title":"Arch Biochem 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