Honey, an apicultural product with a complex chemical composition, contains numerous bioactive compounds with potential antimicrobial effects. This study investigated the effect of Apis mellifera honey from Brazil’s Central-West Region, combined with antibiotics, on bacterial membrane permeability, exploring the contributions of bioactive compounds and the botanical origin of honey. Six fresh Apis mellifera honey samples and their fractions (hexane and ethyl acetate) were analyzed, for a total of 18 samples. The bacteria Staphylococcus epidermidis, Helicobacter pylori and Enterococcus faecalis were used for antibacterial activity tests, which included minimum inhibitory concentration (MIC) determination and synergistic effect (checkerboard) assays. The total polyphenol and flavonoid contents were quantified, and the botanical origin was determined based on pollen analysis. The tested honey samples significantly affected bacterial membrane permeability when combined with rifampicin and clarithromycin. Although many honey-derived bioactive compounds, when isolated, did not exhibit significant activity against these bacteria, the additive or synergistic effect of multiple compounds acting on different targets appears to potentiate the antibacterial action. Descriptive statistical analysis, including means and 95% confidence intervals, confirmed the relevance of the findings. This study has provided an important discovery: Honey has an effect on bacterial membrane permeability, although the specific mechanisms involved in this process require further investigation.
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