The high prevalence of fungal resistance to antifungal drugs necessitates finding new antifungal combinations to boost the antifungal bioactivity of these agents. Hence, the aim of the present investigation was to greenly synthesize zinc oxide nanoparticles (ZnO-NPs) using an aqueous leaf extract of Salvia officinalis and investigate their antifungal activity and synergistic efficiency with common antifungal agents. The biofabricated ZnO-NPs were characterized to detect their physicochemical properties. A disk diffusion assay was employed to investigate the antifungal effectiveness of the greenly synthesized ZnO-NPs and evaluate their synergistic patterns with common antifungal agents. The Candida tropicalis strain was detected to be the most susceptible strain to ZnO-NPs at both tested concentrations of 50 and 100 µg/disk, demonstrating relative suppressive zones of 19.68 ± 0.32 and 23.17 ± 0.45 mm, respectively. The minimum inhibitory concentration (MIC) of ZnO-NPs against the C. tropicalis strain was 40 µg/mL, whereas the minimum fungicidal concentration (MFC) was found to be 80 µg/mL. The highest synergistic efficiency of the biogenic ZnO-NPs with terbinafine antifungal agent was detected against the C. glabrata strain, whereas the highest synergistic efficiency was detected with fluconazole against the C. albicans strain, demonstrating relative increases in fold of inhibition area (IFA) values of 6.82 and 1.63, respectively. Moreover, potential synergistic efficiency was detected with the nystatin antifungal agent against the C. tropicalis strain with a relative IFA value of 1.06. The scanning electron microscopy (SEM) analysis affirmed the morphological deformations of candidal cells treated with the biosynthesized ZnO-NPs as the formation of abnormal infoldings of the cell wall and membranes and also the formation of pores in the cell wall and membranes, which might lead to the leakage of intracellular constituents. In conclusion, the potential synergistic efficiency of the biogenic ZnO-NPs with terbinafine, nystatin, and fluconazole against the tested candidal strains highlights the potential application of these combinations in formulating novel antifungal agents of high antimicrobial efficiency. The biogenic ZnO nanoparticles and antifungal drugs exhibit powerful synergistic efficiency, which highlights their prospective use in the formulation of efficient antimicrobial medications, including mouthwash, ointments, lotions, and creams for effective candidiasis treatment.
Keywords: Salvia officinalis; antifungal; green synthesis; synergism; zinc oxide nanoparticles.