Resumo

Introdution: In the last years, there has been great scientific interest in chemical and pharmacological investigations of the biological properties of medicinal plants. Medicinal plants have been the source of many medications that are now applied in clinical practice. The use of extracts and fractions as antimicrobial agents shows a low risk of increasing resistance to their action, because they are complex mixtures, making microbial adaptability very difficult. Knowledge of medicinal plants is often the only therapeutic resource of many communities and ethnic groups.“Erva-baleeira”, Cordia verbenacea DC., is one of the species of plants currently exploited for the purpose of producing a phytotherapeutic product extracted from its leaves. The present study aimed to establish a chemical profile, antibacterial activity and modulating resistance experimental. Materials and Methods:The phytochemical tests to detect the presence of secondary metabolites were performed according to the method described by Matos. Analysis compounds by HPLC-DAD using Reverse phase chromatographic analyses were carried out under gradient conditions using C18 column (4.6 mm x 150 mm) packed with 5μm diameter particles; the mobile phase was water containing 2% acetic acid (A) and methanol (B), and the composition gradient was: 5% of B until 2 min and changed to obtain 25%, 40%, 50%, 60%, 70% and 100% B at 10, 20, 30, 40, 50 and 80 min, respectively, following the method described by Laghari with slight modifications. Antibacterial test (MIC - Minimal Inhibitory Concentration) and modulation of antibiotic activity was determined in a microdilution assay and determination was carried out in triplicate. The results of the tests were done in triplicate and expressed as geometric mean. Statistical analysis was applied to two-way ANOVA followed by Bonferroni posttests using GraphPad Prism 6.0 software. Results and discussion: The prospecting phytochemical and HPLC analysis of the fractions are in agreement with literature describes when the presence of secondary metabolites (tannins and flavonoids). Natural products (ethyl acetate fractions of methanolic and hexane extract of Cordia verbenacea) showed moderate antibacterial activity when considering the clinical relevance, however when combined with antibiotics was observed synergy, enhancing the antibacterial effect of aminoglycosides. As a result, they can demonstrate a greater interaction with the lipid bilayer of the cell membrane, affecting the respiratory chain and production of energy, or even make the cell more permeable to antibiotics, leading to the interruption of vital cellular activity. These mechanisms of action can be due to the combination of antibiotic with extracts and fractions at a sub-inhibitory concentration added directly to the culture medium. This strategy is called "herbal shotgun" or " synergistic multi-effect targeting" and refers to the utilization of plants and drugs in an approach that utilizes combined mono- or multi-extracts, which can affect not only a single target but various targets, in which the different therapeutic components act together in a synergistic or antagonistic way. This procedure is not only through the combinations of extracts, but also due to combinations between natural products or extracts and synthetic products or antibiotics Conclusion: Our results indicate that the extract and fraction obtained from leaves of C. verbenacea do possess moderate antibacterial activity that is clinically relevant, but when combined with an antibiotic to evaluate their influence on bacterial resistance to aminoglycosides, the fractions (ethyl acetate fractions of methanolic and hexane extract of Cordia verbenacea) demonstrated significant synergistic activity. The use and sale of products derived from C. verbenacea may tend to exert pressure on the populations of this species. Therefore, we recommend the development of management plans for rational and sustainable use of the species, reducing the possible pressure on this species, and more studies with emphasis on the use of the fractions in the treatment of other diseases.