# Ellagic Acid as a Promising Antifungal Agent: A Review of Mechanisms, Synergy, and Formulation Strategies

## TL;DR

Ellagic acid shows strong antifungal potential by targeting multiple pathways and working well with existing drugs, despite challenges in delivery.

## Contribution

The paper reviews ellagic acid's mechanisms, synergistic effects, and formulation strategies as a novel antifungal agent.

## Key findings

- Ellagic acid inhibits fungal growth by disrupting cell walls and plasma membranes.
- It reduces biofilm formation and hyphal development, acting as an antivirulence agent.
- EA synergizes with fluconazole, improving antifungal efficacy and reducing resistance risks.

## Abstract

Ellagic acid (EA), a naturally occurring phenolic compound, has garnered significant interest as a potential antifungal agent owing to increasing fungal resistance and a scarce therapeutic pipeline. This review consolidates the evidence of the broad-spectrum activity of EA against critical priority pathogens, including Candida auris and Cryptococcus neoformans. We highlight its multi-target mechanisms of action, such as the impairment of cell wall integrity and plasma membrane disruption resulting from the inhibition of ergosterol biosynthesis, and inhibition of key enzymes, such as laccase. In addition to its direct growth-inhibitory effects, EA exhibits antivirulence properties, reducing biofilm formation and hyphal morphogenesis. Notably, it demonstrates synergistic potential with conventional antifungals, such as fluconazole, enhancing efficacy and potentially hindering the emergence of resistance. Although its poor solubility and bioavailability pose therapeutic challenges, advanced formulations such as liposomal systems show promise for improving its delivery. We conclude that EA is a promising candidate for developing new antifungal strategies, particularly as a synergistic agent or in nanoformulations, warranting further investigation to translate its potential into clinical practice.