title: Synergistic anti-candidal activity and mode of action of Mentha piperita essential oil and its major components.
abstract: BACKGROUND
  Mentha piperita L. (Lamiaceae) has been used in folk medicine since antiquity. Its essential oil (mint EO) and major bioactive components have antimicrobial properties but their mechanism of action is still not clear.
  
  
  OBJECTIVE
  The present work aims to elucidate M. piperita's anti-Candida activity and mode of action.
  
  
  METHODS
  Chemical constituents of mint EO were identified by GC-MS by injecting 0.1 ml sample in a splitless mode. MIC was determined by the broth dilution method. Synergy with fluconazole (FLC) was evaluated by checkerboard assay and FICI. Mid log phase cells harvested from YPD media were used for proton extrusion measurement and the rate of glucose-induced H(+) efflux gives PM-ATPase activity. Cell membrane integrity was estimated by total ergosterol content and scanning microscopy at respective MIC and sub-MIC values. In vitro hemolytic activity was performed to rule out possible cytotoxicity of the test compounds.
  
  
  RESULTS
  The MIC value of mint EO, carvone, menthol, and menthone was 225, 248, 500, and 4200 µg/ml, respectively. At their respective MICs, these compounds showed 47, 42, 35, and 29% decrease in PM-ATPase activity besides showing synergy with FLC. In case of FLC-resistant strains, the decrease in H(+) efflux was by 52, 48, 32, and 30%, a trend similar to the susceptible cases. Exposed Candida cells showed a 100% decrease in the ergosterol content, cell membrane breakage, and alterations in morphology.
  
  
  CONCLUSIONS
  Our studies suggest that mint EO and its lead compounds exert antifungal activity by reducing ergosterol levels, inhibiting PM-ATPase leading to intracellular acidification, and ultimately cell death. Our results suggest that mint EO and its constituents are potential antifungal agents and need to be further investigated.
authors: Medical Mycology Lab, Department of Biosciences, Jamia Millia Islamia , New Delhi , India and.
authors: Neha
authors: N
authors: Samber
authors: Amber
authors: A
authors: Khan
authors: Ajit
authors: A
authors: Varma
authors: Nikhat
authors: N
authors: Manzoor
mesh_terms: D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D036142:Mentha piperita; D008826:Microbial Sensitivity Tests; D009822:Oils, Volatile / Q000302:isolation & purification / Q000494:pharmacology*; D010938:Plant Oils / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D009822:Oils, Volatile; D010938:Plant Oils; C015424:peppermint oil
keywords: Antifungal activity; Candida; carvone; menthol; menthone; plasma membrane H+-ATPase; synergy; virulence