{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:23:03Z","timestamp":1783344183113,"version":"3.54.6"},"reference-count":68,"publisher":"International Association of Physical Chemists (IAPC)","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ADMET DMPK"],"abstract":"<jats:p>Background and purpose: Microbial resistance is a major global health concern. Methicillin-resistant Staphylococcus aureus is particularly relevant due to its clinical significance, virulence and adaptability. In the search for novel antimicrobial agents, natural products emerged as important sources of bioactive molecules. Previous studies have identified Hypericum brasiliense as a plant with promising antibacterial properties. Experimental approach: We evaluated the susceptibility, mechanisms of action and toxicity of H. brasiliense hexane extract (heHb) and the isolated compounds uliginosin B (uliB), isouliginosin B and japonicin A against reference and drug-resistant S. aureus isolates. Key results: The heHb and uliB demonstrated strong antibacterial activity, exhibiting MICs of 3.125 to 6.25 \u00b5g mL-1 and MBCs of 6.25 to 12.5\u00a0\u00b5g mL-1. Isouliginosin B displayed moderate activity (MIC = 12.5 \u00b5g mL-1; MBC \u226450 \u00b5g mL-1), whereas japonicin A was inactive. Transmission and scanning electron microscopy revealed pronounced ultrastructural alterations in bacterial cells following exposure to either heHb or uliB, and these exposures induced oxidative stress without compromising plasma membrane integrity. Conversely, the antioxidant N-acetylcysteine partially restored bacterial growth. Docking analysis suggested that uliB might act as a competitive substrate for the NADH-2 enzyme and cytochrome bd oxidase. Moreover, heHb and uliB inhibited biofilm formation and disrupted mature biofilms. Cytotoxicity assays (Vero and HaCaT lineages) showed CC\u2085\u2080 &gt;90 \u00b5g mL-1, and haemolysis occurred only at the highest concentrations. In vivo assessment using Galleria mellonella confirmed low toxicity. ADMET predictions indicated a favourable pharmacokinetic profile for uliB. Conclusion: UliB is likely a key bioactive compound of H. brasiliense, with promising therapeutic potential against S. aureus.<\/jats:p>","DOI":"10.5599\/admet.3333","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:09:14Z","timestamp":1783343354000},"source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of action of the hexane extract of &lt;i&gt;Hypericum brasiliense &lt;\/i&gt;and its component uliginosin B against drug-resistant &lt;i&gt;Staphylococcus aureus&lt;\/i&gt;"],"prefix":"10.5599","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6214-7778","authenticated-orcid":false,"given":"Julia","family":"Chaves Scaffo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5215-5864","authenticated-orcid":false,"given":"Sofia","family":"Trindade Mussi da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5303-6814","authenticated-orcid":false,"given":"Vitor","family":"Won-Held Rabelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3715-1967","authenticated-orcid":false,"given":"Leandro","family":"Stefano Sangenito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-8095","authenticated-orcid":false,"given":"Lucas","family":"Da Silva Abreu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5820-2241","authenticated-orcid":false,"given":"Tha\u00eds","family":"P. Mello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-1918","authenticated-orcid":false,"given":"Leandro","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-8592","authenticated-orcid":false,"given":"Andr\u00e9","family":"Luis Souza dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3564","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"187087","doi-asserted-by":"crossref","unstructured":"[1] A. Liu, S. Garrett, W. Hong, J. Zhang. Staphylococcus aureus Infections and Human Intestinal Microbiota. Pathogens 13 (2024) 276. https:\/\/doi.org\/10.3390\/pathogens13040276","DOI":"10.3390\/pathogens13040276"},{"key":"187088","doi-asserted-by":"crossref","unstructured":"[2] B.P. Howden, S.G. Giulieri, T. 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