Mechanisms of action of the hexane extract ofand its component uliginosin B against drug-resistant
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
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 identifiedas a plant with promising antibacterial properties. Experimental approach We evaluated the susceptibility, mechanisms of action and toxicity ofhexane extract (heHb) and the isolated compounds uliginosin B (uliB), isouliginosin B and japonicin A against reference and drug-resistantisolates. Key results The heHb and uliB demonstrated strong antibacterial activity, exhibiting MICs of 3.125 to 6.25 μg mLand MBCs of 6.25 to 12.5 μg mL. Isouliginosin B displayed moderate activity (MIC = 12.5 μg mL; MBC ≤50 μg mL), 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) sho
Abstract
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 identifiedas a plant with promising antibacterial properties. Experimental approach We evaluated the susceptibility, mechanisms of action and toxicity ofhexane extract (heHb) and the isolated compounds uliginosin B (uliB), isouliginosin B and japonicin A against reference and drug-resistantisolates. Key results The heHb and uliB demonstrated strong antibacterial activity, exhibiting MICs of 3.125 to 6.25 μg mLand MBCs of 6.25 to 12.5 μg mL. Isouliginosin B displayed moderate activity (MIC = 12.5 μg mL; MBC ≤50 μg mL), 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, and haemolysis occurred only at the highest concentrations.assessment usingconfirmed low toxicity. ADMET predictions indicated a favourable pharmacokinetic profile for uliB. Conclusion UliB is likely a key bioactive compound of, with promising therapeutic potential against S. aureus.