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The traditional knowledge associated with the use of medicinal plants has significantly contributed to drug development research. In this context, Aloysia gratissima, commonly known as bee-brush or white-brush, has been widely used in Brazilian folk medicine as an analgesic and antimicrobial species. Phytochemical analysis of A. gratissima essential oil has identified sesquiterpene β-caryophyllene (17.3%) as a major component with significant antibacterial activity. Thus, this study aimed to characterize the antibacterial effects of the essential oil obtained from A. gratissima (EOAG) and its major compound β-caryophyllene, as well as to evaluate their potential to act as efflux pumps inhibitors in association with conventional antibiotics. The phytochemical characterization of EOAG was performed by gas chromatography coupled to mass spectrometry (GC-MS), while the antibacterial activity against the strains Pseudomonas aeruginosa 24, Staphylococcus aureus 10, and Escherichia coli 06 was assessed using the broth microdilution method. The antibiotic potentiating activity was investigated by analyzing the ability of the natural products to decrease the minimum inhibitory concentration (MIC) of norfloxacin and ciprofloxacin against S. aureus strains 1199B and K2068. A reduction in the MIC of ethidium bromide in the presence of essential oil components was interpreted as efflux pump inhibition. The GC-MS analysis identified 30 compounds, including β-caryophyllene as the major component. The antibacterial activity analysis demonstrated that both EOAG and β-caryophyllene both EOAG and β-caryophyllene presented antibacterial effects against S. aureus 10 (MIC = 32 μg/mL), in addition to potentiating the activity of norfloxacin against [S. aureus 10], [P. aeruginosa 24], and [E. coli 06]. The isolated compound also reversed the degree of antibiotic resistance observed in strains carrying efflux pumps. In conclusion, the essential oil of A. gratissima and β-caryophyllene have the potential to increase the effectiveness of antibiotics and as such can be used in the development of new therapies against bacterial resistance.

Background: Aloysia gratissima (Verbenaceae), popularly known as bee-brush or whitebrush, has been widely used in Brazilian folk medicine as analgesic, expectorant and antimicrobial. Phytochemical studies have identified β-caryophyllene as one of the major components of the essential oil of this plant. This bioactive sesquiterpene has been shown to have anti-inflammatory and antibacterial activities. Purpose: The present study aimed to characterize the chemical profile and evaluate the antibacterial and antibiotic-enhancing activities of the essential oil obtained from Aloysia gratíssima (EOAG) and β-caryophyllene. Methods: The phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). The antibacterial activity against Pseudomonas aeruginosa 24, Staphylococcus aureus 10, and Escherichia coli 06 was assessed by determining the minimum inhibitory concentration (MIC) using the broth microdilution method. The potentiation of the antibiotic activity by the EOAG and the β-caryophyllene was performed using the MIC evaluation of the antibiotic alone or in association with the essential oil and its main compound. To evaluate the minimum reduction of the drug concentration necessary, the Dose Reduction Index (DRI) was calculated. Results: A reduction in the MIC of the antibiotics against strains treated simultaneously with the essential oil or β-caryophyllene was observed. The GC-MS analysis of the EOAG identified 30 compounds, including β-caryophyllene as the major component. Both OEAG and β-caryophyllene presented antibacterial activity against S. aureus, in addition to potentiating the action of norfloxacin against S. aureus, P. aeruginosa, and E. coli. Conclusions: These substances also reversed the antibiotic resistance to gentamicin and erythromycin against of S. aureus and P. aeruginosa, respectively.

In a recent study, our research group demonstrated that the essential oil of Ocotea odorifera (EOOO) and its major compound safrole potentiated the action fluoroquinolones, modulating bacterial resistance possibly due to direct inhibition of efflux pumps. Thus, in the present study, we investigated whether these treatments could enhance the activity of gentamicin and erythromycin against multidrug-resistant (MDR) bacteria. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC–MS). The antibiotic-enhancing effect of the EOOO and safrole against MDR strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was analyzed by the broth microdilution method. The chemical analysis confirmed the presence of safrole as a major component among the 16 compounds identified in the EOOO. Both the essential oil and the isolated compound showed clinically relevant antibacterial activities against S. aureus. Regarding the modulation of antibiotic resistance, the EOOO was found to enhance the activity of erythromycin against the strains of P. aeruginosa and S. aureus, as well as improving the action of gentamicin against S. aureus. On the other hand, safrole potentiated the activity of gentamicin against the S. aureus strain alone. It is concluded, therefore, that the EOOO and safrole can enhance the activity of macrolides and aminoglycosides, and as such are useful in the development of therapeutic tools to combat bacterial resistance against these classes of antibiotics.

Considering the evidence that essential oils, as well as safrole, could modulate bacterial growth in different resistant strains, this study aims to characterize the phytochemical profile and evaluate the antibacterial and antibiotic-modulating properties of the essential oil Ocotea odor&iacute, fera (EOOO) and safrole against efflux pump (EP)-carrying strains. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). The antibacterial and antibiotic-modulating activities of the EOOO and safrole against resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were analyzed through the broth microdilution method. The EP-inhibiting potential of safrole in association with ethidium bromide or antibiotics was evaluated using the S. aureus 1199B and K2068 strains, which carry genes encoding efflux proteins associated with antibiotic resistance to norfloxacin and ciprofloxacin, respectively. A reduction in the MIC of ethidium bromide or antibiotics was used as a parameter of EP inhibition. The phytochemical analysis identified 16 different compounds in the EOOO including safrole as the principal constituent. While the EOOO and safrole exerted clinically relevant antibacterial effects against S. aureus only, they potentiated the antibacterial activity of norfloxacin against all strains evaluated by our study. The ethidium bromide and antibiotic assays using the strains of S. aureus SA1119B and K2068, as well as molecular docking analysis, indicated that safrole inhibits the NorA and MepA efflux pumps in S. aureus. In conclusion, Ocotea odorifera and safrole presented promising antibacterial and antibiotic-enhancing properties, which should be explored in the development of drugs to combat antibacterial resistance, especially in strains bearing genes encoding efflux proteins.