Antifungal Effects of Pterostilbene on Candida albicans, Candida dubliniensis, and Microcosm Biofilms of Denture Stomatitis

Natural compound-based strategies have gained attention as alternatives to conventional antifungal therapies, particularly in the management of <i>Candida</i> infections affecting the oral cavity, such as denture stomatitis. Our aim was to investigate the antifungal activity of the polyphenol pterostilbene (PTE) on clinical <i>Candida</i> isolates and microcosm biofilms from denture stomatitis, as well as to evaluate its toxicity and therapeutic efficacy in <i>Galleria mellonella</i>. PTE exhibited fungicidal effects against <i>Candida albicans</i> and <i>Candida dubliniensis</i> at 32 µg/mL. Time-kill assays demonstrated complete inhibition of viability for both strains within 8 h of exposure. In addition, PTE exhibited broad-spectrum antimicrobial activity, significantly reducing the counts of streptococci, <i>mutans</i> streptococci, staphylococci, and yeasts within microcosm biofilms. In vivo, PTE showed no signs of toxicity in <i>G. mellonella</i> at concentrations up to 20× MIC. Prophylactic treatment with PTE enhanced larval survival in experimental candidiasis caused by both <i>C. albicans</i> and <i>C. dubliniensis</i>. Moreover, prophylactic treatment decreased the fungal burden of <i>C. albicans</i> in the <i>G. mellonella</i> hemolymph, while the recruitment of hemocytes involved in host defense mechanisms remained unaltered. In summary, PTE demonstrated antimicrobial activity against <i>Candida</i> planktonic cells and complex biofilms associated with denture stomatitis, exhibiting favorable biocompatibility and in vivo antifungal efficacy in <i>G. mellonella</i> model.