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Mol Med Rep ; 10(5): 2341-5, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25189268

RESUMEN

Fraxetin is one of the main constituents of the traditional medicinal plant Fraxinus rhynchophylla. The inhibitory effect of fraxetin on various bacterial strains has been extensively reported, however, its mechanism of action on bacterial cells remains to be elucidated. In the present study, the antibacterial mechanism of fraxetin on Staphylococcus aureus was systematically investigated by examining its effect on cell membranes, protein synthesis, nucleic acid content and topoisomerase activity. The results indicated that fraxetin increased the permeability of the cell membrane but did not render it permeable to macromolecules, such as DNA and RNA. Additionally, the quantity of protein, DNA and RNA decreased to 55.74, 33.86 and 48.96%, respectively following treatment with fraxetin for 16 h. The activity of topoisomerase I and topoisomerase II were also markedly inhibited as fraxetin concentration increased. The result of the ultraviolet­visible spectrophotometry demonstrated that the DNA characteristics exhibited a blue shift and hypochromic effect following treatment with fraxetin. These results indicated that fraxetin had a marked inhibitory effect on S.aureus proliferation. Further mechanistic studies showed that fraxetin could disrupt nucleic acid and protein synthesis by preventing topoisomerase from binding to DNA.


Asunto(s)
Antibacterianos/farmacología , Cumarinas/farmacología , Inhibidores de la Síntesis de la Proteína/farmacología , Staphylococcus aureus/efectos de los fármacos , Proteínas Bacterianas/biosíntesis , Membrana Celular/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , Enzimas de Restricción del ADN/antagonistas & inhibidores , Enzimas de Restricción del ADN/metabolismo , ADN-Topoisomerasas/metabolismo , ADN Bacteriano/biosíntesis , Viabilidad Microbiana/efectos de los fármacos , Unión Proteica , Biosíntesis de Proteínas/efectos de los fármacos , Mapeo Restrictivo , Staphylococcus aureus/metabolismo , Inhibidores de Topoisomerasa/farmacología
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