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Synergistic Effects of Cepharanthine and Amphotericin B Against Candida albicans by Targeting PMP3-Mediated

Song Wang1, Qiya Zhang1, Qinlan Li1

  • 1College of Stomatology of Guizhou Medical University, Guiyang, 550004, China.

Mycopathologia
|July 23, 2026
PubMed

Insights

Cepharanthine combined with amphotericin B shows synergistic effects against Candida albicans, inhibiting growth and biofilm formation. This combination targets fungal membrane integrity, offering a promising treatment for oral candidiasis.

Area of Science:

  • Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Candida albicans causes challenging mucosal infections like oral candidiasis.
  • Limited antifungal drugs, resistance, and toxicity necessitate combination therapies.
  • Cepharanthine (CEP) and amphotericin B (AmB) are potential agents for combination therapy.

Purpose of the Study:

  • To investigate the synergistic effect of cepharanthine and amphotericin B against Candida albicans.
  • To elucidate the mechanism of action for this drug combination.
  • To evaluate the combination's efficacy in inhibiting fungal growth, metabolism, and biofilm formation.

Main Methods:

  • Checkerboard method to determine minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI).
  • Transcriptome sequencing, membrane permeability assays, mitochondrial membrane potential assessment, and scanning electron microscopy.
  • RT-qPCR analysis and molecular docking to investigate gene expression and drug-protein interactions.

Main Results:

  • The combination of cepharanthine and amphotericin B exhibited synergistic effects (FICI < 0.5) against standard and clinical Candida albicans strains.
  • The combination significantly inhibited fungal metabolism, hyphal growth, and biofilm formation.
  • Cepharanthine targets the fungal membrane, downregulating PMP3 gene expression involved in sphingolipid synthesis, thus compromising cell integrity.

Conclusions:

  • Cepharanthine and amphotericin B combination therapy demonstrates significant synergistic activity against Candida albicans.
  • The mechanism involves disruption of fungal cell membrane integrity through suppressed sphingolipid synthesis.
  • This combination represents a promising therapeutic strategy for managing oral candidiasis.
Keywords:
Candida albicansAmphotericin BCell membraneCepharanthinePMP3 gene

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