ABSTRACT
The species Cordia verbenacea DC (Boraginaceae), known as the whaling herb and camaradinha, is a perennial shrub species native to the Atlantic Forest. Its leaves are used in folk medicine as an anti-inflammatory, analgesic, antiulcerogenic and curative agent, in the form of teas or infusions for internal or topical use. The present study aimed to verify the cytotoxicity of the essential oil and the leishmanicidal and trypanocidal potential of C. verbenacea. The essential oil was characterized by GC-MS. The in vitro biological activity was determined by anti-Leishmania and anti-Trypanosoma assays. The cytotoxixity was determined using mammalian fibroblasts. The C. verbenacea species presented α-pinene (45.71%), ß-caryophyllene (18.77%), tricyclo[2,2,1-(2.6)]heptane (12.56%) as their main compounds. The essential oil exhibited strong cytotoxicity at concentrations below 250 µg/mL (LC50 138.1 µg/mL) in mammalian fibroblasts. The potent anti-trypanosome and anti-promastigote activities occurred from the concentration of 62.5 µg/mL and was considered clinically relevant. The results also demonstrate that at low concentrations (<62.5 µg/mL), the essential oil of C. verbenacea managed to be lethal for these activities. This can be considered an indication of the power used in daily human consumption. Therefore, it can be concluded that the essential oil of C. verbenacea contains a compound with remarkable antiparasitic activities and requires further research.
Subject(s)
Cordia/chemistry , Cytotoxins , Leishmania braziliensis/growth & development , Oils, Volatile , Trypanocidal Agents , Trypanosoma cruzi/growth & development , Animals , Cell Line , Cytotoxins/chemistry , Cytotoxins/isolation & purification , Cytotoxins/pharmacology , Mice , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Oils, Volatile/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/isolation & purification , Trypanocidal Agents/pharmacologyABSTRACT
Resistance to antibiotics has made diseases that previously healed easily become more difficult to treat. Staphylococcus aureus is an important cause of hospital-acquired infections and multi-drug resistant. NorA efflux pump, present in bacteria S. aureus, is synthesized by the expression of the norA gene. Menadione, also known as vitamin K3, is one of the synthetic forms of vitamin K. Therefore, the aim of this study is to verify the menadione effect on efflux inhibition through NorA pump gene expression inhibition and assess the effects of menadione in bacterial membrane. The effect of menadione as an efflux pump inhibitor (EPI) was evaluated by the microdilution method, fluorimetry, electron microscopy, and by RT-qPCR to evaluate gene expression. In the molecular docking, association with menadione induces increased fluorescence intensity. Menadione was observed (100% of the clusters) interacting with residues ILE12, ILE15, PHE16, ILE19, PHE47, GLN51, ALA105, and MET109 from NorA. The results showed the norA gene had its expression significantly diminished in the presence of menadione. The simulation showed that several menadione molecules were able to go through the bilayer and allow the entry of water molecules into the hydrophobic regions of the bilayer. When present within membranes, menadione may have caused membrane structural changes resulting in a decline of the signaling pathways involved in norA expression. Menadione demonstrated to be an efflux pump inhibitor with dual mechanism: affecting the efflux pump by direct interaction with protein NorA and indirectly inhibiting the norA gene expression, possibly by affecting regulators present in the membrane altered by menadione.
