title: Natural Terpenes Influence the Activity of Antibiotics against Isolated Mycobacterium tuberculosis.
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.
  
  
  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.
authors.affiliation: Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: Elwira
authors.initials: E
authors.lastname: Sieniawska
authors.forename: Marta
authors.initials: M
authors.lastname: Swatko-Ossor
authors.forename: Rafał
authors.initials: R
authors.lastname: Sawicki
authors.forename: Krystyna
authors.initials: K
authors.lastname: Skalicka-Woźniak
authors.forename: Grazyna
authors.initials: G
authors.lastname: Ginalska
mesh_terms: D000080462:Acyclic Monoterpenes; D000475:Alkenes / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology*; D000081008:Bicyclic Monoterpenes; D053138:Cyclohexenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D000077222:Limonene; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000080462:Acyclic Monoterpenes; D000475:Alkenes; D000995:Antitubercular Agents; D000081008:Bicyclic Monoterpenes; D053138:Cyclohexenes; D039821:Monoterpenes; D012717:Sesquiterpenes; D013729:Terpenes; C445979:beta-elemene; C509595:myrcene; C035127:sabinene; D004977:Ethambutol; D000077222:Limonene; C005451:alpha-pinene; D007538:Isoniazid; D012293:Rifampin