Background: Microbial resistance to antibiotics is a global public health problem, which requires urgent
attention. Platonia insignis is a native species from the eastern Brazilian Amazon, used in the treatment of burns and
Objectives: To evaluate the antimicrobial activity of the hydroalcoholic extract of P. insignis (PIHA), the ethyl acetate
fraction (PIAE), and its subfraction containing a mixture of biflavonoids (BF). Moreover, the effect of these
natural products on the antibiotic activity against S. aureus strains overexpressing efflux pump genes was also evaluated.
Methods: Minimal inhibitory concentrations were determined against different species of microorganisms. To evaluate
the modulatory effect on the Norfloxacin-resistance, the MIC of this antibiotic was determined in the absence and
presence of the natural products at subinhibitory concentrations. Inhibition of the EtBr efflux assays were conducted
in the absence or presence of natural products.
Results: PIHA showed a microbicidal effect against S. aureus and C. albicans, while PIAE was bacteriostatic for S.
aureus. PIAE and BF at subinhibitory concentrations were able to reduce the MIC of Norfloxacin acting as modulating
agents. BF was able to inhibit the efflux of EtBr efflux in S. aureus strains overexpressing specific efflux pump
Conclusion: P. inignisis, a source of efflux pump inhibitors, including volkensiflavone and morelloflavone, which
were able to potentiate the Norfloxacin activity by NorA inhibition, being also able to inhibit QacA/B, TetK and
MsrA. Volkensiflavone and morelloflavone could be used as an adjuvant in the antibiotic therapy of multidrug resistant
S. aureus strains overexpressing efflux pumps.