ReviewArticle: The in vivo Anti-Candida albicans Activity of Flavonoids.

Abstract Background Emerging drug-resistant strains of Candida albicans have led to the recurrence of fungal disease, rendering conventional drug therapies ineffective. Although in vitro studies on flavonoids as novel antifungal products have shown promising results, there is currently limited information regarding their in vivo effects. The aim of this review is to evaluate in vivo studies on the antifungal activity of flavonoids against C. albicans, as novel therapeutic agents. In this regard, we conducted broad searches of PubMed, Web of Science, and Embase covering the years 2009–2020. Highlight : Flavonoids represent new natural therapeutic compounds to treat oral candidiasis. Among subclasses of flavonoids, flavonols and chalcones appear to have the most significant antifungal activities. Oral administration of Canthin-6-one, a flavonol, has the potential to damage fungal cell membrane while having minimal toxic effects on mice. Similarly, topical oral application of lichochalcone-A, a chalcone, reduces oral candidiasis in mice. There appears to be structural similarities in the hydroxyl residues among compounds within the same subclass of flavonoids, which may contribute to antibiofilm activity. Oral topical application of flavonoids shows low toxicity and has clinical relevance as potential novel antifungal treatments. Conclusion Flavonoids are a group of natural products exhibiting antifungal activity. The subclasses flavonols and chalcones appear to have the most significant in vivo antifungal activity against C. albicans infections in mouse models. Specifically, quercetin (flavonol) has been applied via vaginal gavage in a murine vulvovaginal candidiasis model, whereas lichochalcone-A (chalcone) has shown topical oral application in C. albicans-inoculated mice. Both compounds show efficacy in fungal elimination via biofilm inhibition for their respective subclasses. The translational significance of these in vivo studies should be examined in clinical trials of selected potent compounds for the treatment of oral candidiasis. Further studies are necessary to elucidate the specific mechanisms of flavonoids as antifungal agents.