Synergistic antifungal effect of glabridin and fluconazole

PLoS One. 2014 Jul 24;9(7):e103442. doi: 10.1371/journal.pone.0103442. eCollection 2014.

Abstract

The incidence of invasive fungal infections is increasing in recent years. The present study mainly investigated glabridin (Gla) alone and especially in combination with fluconazole (FLC) against Cryptococcus neoformans and Candida species (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis and Candida Glabratas) by different methods. The minimal inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) indicated that Gla possessed a broad-spectrum antifungal activity at relatively high concentrations. After combining with FLC, Gla exerted a potent synergistic effect against drug-resistant C. albicans and C. tropicalis at lower concentrations when interpreted by fractional inhibitory concentration index (FICI). Disk diffusion test and time-killing test confirming the synergistic fungicidal effect. Cell growth tests suggested that the synergistic effect of the two drugs depended more on the concentration of Gla. The cell envelop damage including a significant decrease of cell size and membrane permeability increasing were found after Gla treatment. Together, our results suggested that Gla possessed a synergistic effect with FLC and the cell envelope damage maybe contributed to the synergistic effect, which providing new information for developing novel antifungal agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Candida / classification
  • Candida / drug effects*
  • Candida / growth & development
  • Cell Wall / drug effects
  • Cryptococcus neoformans / drug effects*
  • Cryptococcus neoformans / growth & development
  • Dose-Response Relationship, Drug
  • Drug Resistance, Fungal / drug effects
  • Drug Synergism
  • Fluconazole / pharmacology*
  • Isoflavones / pharmacology*
  • Microbial Sensitivity Tests
  • Phenols / pharmacology*

Substances

  • Antifungal Agents
  • Isoflavones
  • Phenols
  • Fluconazole
  • glabridin

Grants and funding

This study was supported by National Key Basic Research Program of China (No 2013CB531602), the National Science Foundation of China (81202563, 81330083), National Science and Technology Major Project for the Creation of New Drugs (No 2012ZX09103101-003), and China posdoctoral Science foundation grant (No 2012M511141). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.