Insight into the Antifungal Effects of Propolis and Carnosic Acid-Extension to the Pathogenic Yeast Candida glabrata: New Propolis Fractionation and Potential Synergistic Applications

Fungi have traditionally been considered opportunistic pathogens in primary infections caused by virulent bacteria, protozoan, or viruses. Consequently, antimycotic chemotherapy is clearly less developed in comparison to its bacterial counterpart. Currently, the three main families of antifungals (polyenes, echinocandins, and azoles) are not sufficient to control the enormous increase in life-threatening fungal infections recorded in recent decades. Natural substances harvested from plants have traditionally been utilized as a successful alternative. After a wide screening of natural agents, we have recently obtained promising results with distinct formulations of carnosic acid and propolis on the prevalent fungal pathogens Candida albicans and Cryptococcus neoformans. Here, we extended their use to the treatment against the emerging pathogenic yeast Candida glabrata, which displayed lower susceptibility in comparison to the fungi mentioned above. Taking into account the moderate antifungal activity of both natural agents, the antifungal value of these combinations has been improved through the obtention of the hydroethanolic fractions of propolis. In addition, we have demonstrated the potential clinical application of new therapeutical designs based on sequential pre-treatments with carnosic/propolis mixtures, followed by exposure to amphotericin B. This approach increased the toxic effect induced by this polyene.

Automated summary

Fungi have traditionally been considered opportunistic pathogens in primary infections caused by other virulent microorganisms, such as bacteria, protozoa, or viruses. Antimycotic chemotherapy lags behind antibacterial therapy, but natural substances from plants have shown promise as alternative treatments. Recent research has identified the antifungal potential of carnosic acid and propolis against Candida albicans, Cryptococcus neoformans, and Candida glabrata, with improved efficacy when combined with hydroethanolic fractions of propolis. Sequential pre-treatments with carnosic acid/propolis mixtures followed by exposure to amphotericin B have also shown increased effectiveness against fungal infections.