{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:07:03Z","timestamp":1775581623554,"version":"3.50.1"},"reference-count":100,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Betulinic acid is a naturally occurring compound that can be obtained through methanolic or ethanolic extraction from plant sources, as well as through chemical synthesis or microbial biotransformation. Betulinic acid has been investigated for its potential therapeutic properties, and exhibits anti-inflammatory, antiviral, antimalarial, and antioxidant activities. Notably, its ability to cross the blood\u2013brain barrier addresses a significant challenge in treating neurological pathologies. This review aims to compile information about the impact of betulinic acid as an antitumor agent, particularly in the context of glioblastoma. Importantly, betulinic acid demonstrates selective antitumor activity against glioblastoma cells by inhibiting proliferation and inducing apoptosis, consistent with observations in other cancer types. Compelling evidence published highlights the acid\u2019s therapeutic action in suppressing the Akt\/NF\u03baB-p65 signaling cascade and enhancing the cytotoxic effects of the chemotherapeutic agent temozolomide. Interesting findings with betulinic acid also suggest a focus on researching the reduction of glioblastoma\u2019s invasiveness and aggressiveness profile. This involves modulation of extracellular matrix components, remodeling of the cytoskeleton, and secretion of proteolytic proteins. Drawing from a comprehensive review, we conclude that betulinic acid formulations as nanoparticles and\/or ionic liquids are promising drug delivery approaches with the potential for translation into clinical applications for the treatment and management of glioblastoma.<\/jats:p>","DOI":"10.3390\/ijms25042108","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T08:12:03Z","timestamp":1707466323000},"page":"2108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2031-0658","authenticated-orcid":false,"given":"S\u00edlvia","family":"Fernandes","sequence":"first","affiliation":[{"name":"Center for Translational Health and Medical Biotechnology Research (TBIO), School of Health (ESS), Polytechnic University of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-072 Porto, Portugal"},{"name":"Center for Research on Health and Environment (CISA), School of Health (ESS), Polytechnic University of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6199-6822","authenticated-orcid":false,"given":"Mariana","family":"Vieira","sequence":"additional","affiliation":[{"name":"Center for Translational Health and Medical Biotechnology Research (TBIO), School of Health (ESS), Polytechnic University of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9920-936X","authenticated-orcid":false,"given":"Cristina","family":"Prud\u00eancio","sequence":"additional","affiliation":[{"name":"Center for Translational Health and Medical Biotechnology Research (TBIO), School of Health (ESS), Polytechnic University of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-072 Porto, Portugal"},{"name":"Ci\u00eancias Qu\u00edmicas e das Biomol\u00e9culas, School of Health (ESS), Polytechnic University of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1761-117X","authenticated-orcid":false,"given":"Ricardo","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Center for Translational Health and Medical Biotechnology Research (TBIO), School of Health (ESS), Polytechnic University of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-072 Porto, Portugal"},{"name":"Ci\u00eancias Qu\u00edmicas e das Biomol\u00e9culas, School of Health (ESS), Polytechnic University of Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-072 Porto, Portugal"},{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2120277119","DOI":"10.1073\/pnas.2120277119","article-title":"Plants protect themselves from herbivores by optimizing the distribution of chemical defenses","volume":"119","author":"Gershenzon","year":"2022","journal-title":"Proc. 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