ADMET and DMPK, Vol. 14 , 2026.
Original scientific paper
https://doi.org/https://doi.org/10.5599/admet.3333
Mechanisms of action of the hexane extract of Hypericum brasiliense and its component uliginosin B against drug-resistant Staphylococcus aureus
Julia Chaves Scaffo
; Graduate Program in Applied Sciences for Health Products, Faculty of Pharmacy, Fluminense Federal University (UFF), Niterói, Brazil;
Sofia Trindade Mussi da Silva
; Laboratory of Chemistry of Natural Products, Institute of Chemistry, Fluminense Federal University (UFF), Niterói, Brazil
Vitor Won-Held Rabelo
; Department of Virology, Paulo de Góes Microbiology Institute, Center of Health Science, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
Leandro Stefano Sangenito
; Laboratory of Advanced Studies of Emerging and Resistant Microorganisms, Paulo de Góes Microbiology Institute, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
Lucas da Silva Abreu
; Laboratory of Chemistry of Natural Products, Institute of Chemistry, Fluminense Federal University (UFF), Niterói, Brazil
Thaís P. Mello
; Collection of Environment and Health Fungi (CFAS), Fungal Section, Department of Microbiology, National Institute for Quality Control in Health (INCQS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil
Leandro Rocha
; Graduate Program in Applied Sciences for Health Products, Faculty of Pharmacy, Fluminense Federal University (UFF), Niterói, Brazil;
André Luis Souza dos Santos
; Laboratory of Advanced Studies of Emerging and Resistant Microorganisms, Paulo de Góes Microbiology Institute, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
*
* Corresponding author.
Abstract
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 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. Conclusion: UliB is likely a key bioactive compound of H. brasiliense, with promising therapeutic potential against S. aureus.
Keywords
Natural products; antimicrobial activity; bacterial infections; biofilm, toxicity; Galleria mellonella
Hrčak ID:
350220
URI
Publication date:
6.7.2026.
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