Natural Terpenes Influence the Activity of Antibiotics against Isolated Mycobacterium tuberculosis

Med Princ Pract. 2017;26(2):108-112. doi: 10.1159/000454680. Epub 2016 Nov 23.

Abstract

Objective: In this study, we aimed to describe the influence of natural terpenes on the antimycobacterial activity of first-line tuberculostatic drugs against isolated Mycobacterium tuberculosis.

Materials and methods: The natural terpenes used in this study were R-limonene, S-limonene, myrcene, sabinene, α-pinene, and β-elemene. The values of the minimum inhibitory concentration (MIC) for these terpenes, as well as for combinations of terpenes with tuberculostatic antibiotics (ethambutol, isoniazid, and rifampicin), were determined using a tube log2 dilution method in the range of 125-0.059 µg/mL.

Results: S-limonene had a strong synergistic effect with all tested antibiotics (MIC decreased from 16 to 0.475 µg/mL for ethambutol, from 16 to 0.237 µg/mL for rifampicin, and from 32 to 0.475 µg/mL for isoniazid). Combinations of myrcene, R-limonene, β-elemene, and sabinene with tuberculostatic antibiotics resulted in a decreased MIC of the antibiotics (from 3.9 to 0.475 µg/mL for ethambutol, from 15 to 0.475 µg/mL for isoniazid, and from 0.475 to 0.237 µg/mL for rifampicin) while combinations of α-pinene with ethambutol and isoniazid resulted in increased MIC values (from 16 to 125 µg/mL for ethambutol, and from 32 to 125 µg/mL for isoniazid). Rifampicin had a synergistic increase in activity with all the tested compounds.

Conclusions: Our study showed that terpenes enhance the activity of tuberculostatic antibiotics.

MeSH terms

  • Acyclic Monoterpenes
  • Alkenes / pharmacology
  • Antitubercular Agents / pharmacology*
  • Bicyclic Monoterpenes
  • Cyclohexenes / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Ethambutol / pharmacology
  • Humans
  • Isoniazid / pharmacology
  • Limonene
  • Microbial Sensitivity Tests
  • Monoterpenes / pharmacology
  • Mycobacterium tuberculosis / drug effects*
  • Rifampin / pharmacology
  • Sesquiterpenes / pharmacology
  • Terpenes / pharmacology*

Substances

  • Acyclic Monoterpenes
  • Alkenes
  • Antitubercular Agents
  • Bicyclic Monoterpenes
  • Cyclohexenes
  • Monoterpenes
  • Sesquiterpenes
  • Terpenes
  • beta-elemene
  • myrcene
  • sabinene
  • Ethambutol
  • Limonene
  • alpha-pinene
  • Isoniazid
  • Rifampin