Dehydrozingerone enhances the fungicidal activity of glabridin againstSaccharomyces cerevisiaeandCandida albicans

Abstract

AbstractDrug resistance commonly occurs when treating immunocompromized patients with fungal infections. Dehydrozingerone—a phenolic compound isolated from the rhizome of Zingiber officinale—inhibits drug efflux in Saccharomyces cerevisiae by overexpression of the ATP-binding cassette (ABC) transporter Pdr5p. We aimed to investigate whether dehydrozingerone enhances the antifungal activity of glabridin—an isoflavan isolated from the roots of Glycyrrhiza glabra L.—by attenuating multidrug resistance through the intrinsic expression system of multidrug-efflux-related genes in a wild-type strain of the model yeast. The antifungal activity of 50 μmol l−1 glabridin alone was weak and temporary against S. cerevisiae; however, cell viability was significantly inhibited when the cells were co-treated with glabridin and dehydrozingerone. This enhancement was also observed in human pathogenic Candida albicans. Glabridin efflux did not depend on a particular drug efflux pump; instead, the transcription factors PDR1 and PDR3—regulating the transcription of multiple genes encoding drug efflux pumps—were involved in the antifungal activity and efflux of glabridin. qRT–PCR analysis revealed that dehydrozingerone reduced glabridin-induced overexpression of the ABC transporter-related genes PDR1, PDR3, and PDR5 to the levels observed in untreated cells. Our findings indicated that dehydrozingerone potentiates the efficacy of plant-derived antifungals through its effects on ABC transporters.