Comparative analysis of the antibacterial and drug-modulatory effect of d-limonene alone and complexed with β-cyclodextrin

Eur J Pharm Sci. 2019 Feb 1;128:158-161. doi: 10.1016/j.ejps.2018.11.036. Epub 2018 Nov 30.


With the increase in bacterial resistance to antibiotics, many studies have been directed towards finding new agents with antibacterial activity, such as studies with natural products. These products can have antibacterial activity such as d-limonene as described in the literature. The aim of this study was to evaluate the antibacterial activity of d-limonene, isolated and complexed with β-cyclodextrin, and to evaluate its potentiating activity of different antibiotic classes. Antibacterial activity was determined by the broth microdilution method, obtaining in this way the Minimal Inhibitory Concentration (MIC), with the antibiotic modulatory activity being obtained using a sub-inhibitory concentration (MIC/8). d-Limonene showed a MIC equal to 256 μg/mL against standard S. aureus and 512 μg/mL against resistant P. aeruginosa. In the gentamicin modulatory activity, the isolated d-limonene presented synergism against S. aureus and E. coli bacteria. Thus, d-limonene showed relevant clinical antibacterial activity, for both Gram-positive and Gram-negative bacteria as well as a synergistic effect when associated with gentamicin. These results are promising in the combat against bacterial resistance, however further studies are needed to better elucidate the mechanisms of action.

Keywords: Bacterial resistance; Escherichia coli; Pseudomonas aeruginosa; Staphylococcus aureus.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Limonene / chemistry*
  • Limonene / pharmacology*
  • beta-Cyclodextrins / chemistry*


  • Anti-Bacterial Agents
  • beta-Cyclodextrins
  • Limonene
  • betadex