Mechanisms of action of the hexane extract of Hypericum brasiliense and its component uliginosin B against drug-resistant Staphylococcus aureus.

Authors

Julia Chaves Scaffo, Sofia Trindade Mussi da Silva, Vitor Won-Held Rabelo, Leandro Stefano Sangenito, Lucas da Silva Abreu, Thaís P Mello, Leandro Rocha, André Luis Souza Dos Santos

Published in

ADMET & DMPK. Volume 14. Pages 3333. Epub Jul 06, 2026.

Abstract

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.
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.
The heHb and uliB demonstrated strong antibacterial activity, exhibiting MICs of 3.125 to 6.25 μg mL^-1 and MBCs of 6.25 to 12.5 μg mL^-1. Isouliginosin B displayed moderate activity (MIC = 12.5 μg mL^-1; MBC ≤50 μg 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 CC₅₀ >90 μg 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.
UliB is likely a key bioactive compound of H. brasiliense, with promising therapeutic potential against S. aureus.

PMID:
42633493
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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