Assessment of silibinin as a potential antifungal agent and investigation of its mechanism of action

IUBMB Life. 2017 Aug;69(8):631-637. doi: 10.1002/iub.1647. Epub 2017 Jun 21.

Abstract

Silibinin, which is derived from Silybum marianum (milk thistle), has used as a traditional remedy for liver or biliary disorders and known to have superior antioxidant activity. In addition, silibinin was recently reported to have antifungal effect related to fungal apoptosis against Candida albicans and the interest in the therapeutic effect is increasing. In this study, we found another mode of antifungal action of silibinin and its antibiofilm activity on C. albicans. To investigate influence on fungal plasma membrane, propidium iodide and bis-(1, 3-dibutylbarbituric acid) trimethineoxonol [DiBAC4 (3)] assay were primarily carried out. After 5-h incubation with silibinin (50, 100, 150, or 200 µg/mL), the propidium iodide fluorescent percentages increased by 11.90%, 28.50%, 34.10%, and 44.52%, respectively, and the DiBAC4 (3) fluorescent percentages increased by 13.18%, 34.64%, 46.99%, and 57.15%, respectively. As a result, we thought that silibinin concentrations of more than 100 µg/mL have a membrane-damaging effect. Subsequently, to estimate the degree of membrane damage, we used Fluorescein isothiocyanate-labelled dextrans (FDs) of various sizes and the results indicated that silibinin allowed penetration of molecules smaller than approximately FD20 (3.3 nm). In addition, silibinin inhibited the dimorphic transition of C. albicans and resulted in the inhibition of biofilm development at an early stage. In conclusion, we found membrane-damaging effect of silibinin and its antibiofilm effect in C. albicans. © 2017 IUBMB Life, 69(8):631-637, 2017.

Keywords: Candida albicans; antibiofilm; membrane disruption; silibinin.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Candida albicans / drug effects*
  • Candida albicans / pathogenicity
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Cell Membrane / drug effects
  • Fluorescent Dyes / chemistry
  • Humans
  • Membrane Potentials / drug effects
  • Propidium / chemistry
  • Silybin
  • Silymarin / chemistry
  • Silymarin / pharmacology*

Substances

  • Antifungal Agents
  • Antioxidants
  • Fluorescent Dyes
  • Silymarin
  • Propidium
  • Silybin