Fungistatic Potential and Inhibition of Fungal Yeast-hyphae switch of Candida spp. by Hecogenin Acetate

Invasive fungal infections represent one of the leading causes of morbidity and mortality in immunocompromised patients, and many of the currently available antifungal agents are associated with toxicity, recurrence, or the development of resistance. Plants are a promising source for the discovery of new antifungal compounds due to their vast chemical diversity, among which saponins are widely distributed metabolites. Hecogenin acetate is a sapogenin-the hydrophobic moiety of saponins-and has demonstrated antioxidant, antinociceptive, anti-inflammatory, antifungal, and antihypertensive properties. This study aimed to evaluate the susceptibility of fungal strains to hecogenin acetate, assess its combination with a reference drug using the broth microdilution method, and analyze morphological changes from yeast to filamentous forms (hyphae and pseudohyphae) in Candida albicans, Candida tropicalis, and Candida krusei strains through microculture. The results revealed that hecogenin acetate exhibited fungistatic activity, although it showed a higher IC₅₀ compared to fluconazole. When combined with fluconazole, hecogenin acetate did not reduce the drug's efficacy against C. tropicalis, but it did reduce it against C. krusei. Hecogenin acetate displayed lower inhibition of growth inhibition than fluconazole and decreased its effectiveness in this aspect; however, it completely inhibited fungal yeast-hyphae switch at its highest concentration. These findings suggest that hecogenin acetate may provide complementary benefits, particularly due to its fungistatic effect and ability to inhibit fungal virulence.